Background: A plethora of data supports HPV-based screening to be the preferred strategy for cervical cancer prevention. The shift to a more sensitive firstline test brings the need of effective triage up for discussion. Currently, most algorithms apply cytology as triage of HPV-DNA positive women. This study compared the performance of a 7-type HPV-mRNA test to cytology. Methods: From 2019-01-01, until 2021-12-31, cervical samples from 58,029 women were examined at the University Hospital of North Norway. 30.5% (17,684/58,029) fulfilled the criteria for HPV-DNA primary screening. All positive samples were triaged by cytology and followed-up according to national guidelines through 2022. Additionally, a 7-type HPV-mRNA test was applied. Study endpoint was histologically confirmed high grade lesion (CIN2+). Results: 5.6% (990/17,684) had positive HPV-DNA test, 97.2% (962/990) with valid HPV-mRNA results. 55.5% (534/962) had abnormal cytology (ASC-US+) and 35.1% (338/962) had positive HPV-mRNA test. 13.9% (134/962) had CIN2+. Sensitivity (CIN2+) of cytology versus the HPV-mRNA test was 76.1% (102/134)) versus 73.1% (98/134)), p=0.67. The specificity was 47.8% (396/828) versus 71.0% (588/624), p<0.001. PPV was 19.1% (102/534) and 29.0% (98/338), p<0.001 respectively. The number of colposcopies per CIN2+ detected by cytology and HPV-mRNA test was 5.2 and 3.1. Conclusion: The 7-type HPV mRNA test was significant more specific than cervical cytology in triage of HPV-DNA positive women. Using this biomarker as threshold for colposcopy may better balance the benefits and harms of screening.

Human papillomavirus testing is increasingly central to screening programs for cervical cancer. Although HPV testing has excellent clinical sensitivity it suffers from modest clinical specificity. Cytology has taken an important role as a triage test, while more recently HPV16/18 genotyping has provided modest incremental benefits. Despite such progress issues remain to be addressed, some of which are how to: 1) improve access to the best methods, 2) decrease costs so more women can be screened, 3) simplify management algorithms, 4) Recognize the evolving diagnostic landscape created by widespread HPV vaccination. Part of the solution lies in improving the positive predictive value of the initial screen and reflex triage. An aspirational goal should be that most women attending colposcopy have true precancer; DNA methylation testing has a role to play here. Cervical cancers and CIN2/3 generally have high levels of methylation in target human and HPV genes. In contrast normal and healthy women with no intraepithelial lesions or malignancy usually have low methylation. Furthermore, there is an interesting and useful secular gradient of increasing cervical DNA methylation as women progress toward precancer and cancer. Recent results from clinical studies using commercially available routine qPCR-based DNA methylation tests have been encouraging, demonstrating the potential for higher sensitivity and specificity than current triage methods.

The presence of mutated genes strongly correlates with the incidence of cancer. Decades of research, however, has not yielded any specific causative gene or set of genes for the vast majority of cancers. The Cancer Genome Atlas program was supposed to provide clarity but it only gave much more data without any accompanying insight into how the disease begins and progresses. It may be time to notice that epidemiological studies consistently show that the environment, not genes, has the principal role in causing cancer. Since carcinogenic chemicals in our food, drink, air and water are the primary culprits, we need to look at the biochemistry of cancer, with a focus on enzymes which invariably facilitate transformations in a cell. In particular, attention should be paid to the rate-limiting enzyme in DNA synthesis, ribonucleotide reductase (RnR) whose activity is tightly linked to tumor growth. Besides circumstantial evidence that cancer is induced at this enzyme’s vulnerable free-radical-containing active-site by various carcinogens, its role in initiating retinoblastoma and HPV-related cervical cancers is well documented. Blocking the activity of malignant RnR is a certain way to arrest cancer.

Background: Human papillomavirus (HPV) is responsible for most cervical cancer cases globally, with women living with HIV at higher risk of persistent HPV infection and HPV-associated disease. The HPV vaccine is a promising solution to reducing cervical cancer rates, but its uptake among women living with HIV in Nigeria is unknown. Methods: A facility-based, cross-sectional survey was conducted with 1,371 women living with HIV to assess their knowledge of HPV, cervical cancer, and the HPV vaccine, as well as their willingness to pay for the vaccine at the HIV treatment clinic, Nigerian Institute of Medical Research, Lagos. Willingness to pay for the HPV vaccine was also assessed. Multivariable logistic regression models were developed to identify factors associated with willingness to pay for the HPV vaccine. Results: The study found that 79.1% of participants had not heard of the vaccine, and only 29.0% knew of its efficacy in preventing cervical cancer. Moreover, 68.3% of participants were unwilling to pay for the vaccine, and the average amount they were willing to pay was low. Knowledge of HPV, the HPV vaccine, cervical cancer, and income were factors associated with willingness to pay for the vaccine. Health workers were the primary source of information. Conclusion: The study found that 79.1% of participants had not heard of the vaccine, and only 29.0% knew of its efficacy in preventing cervical cancer. Moreover, 68.3% of participants were unwilling to pay for the vaccine, and the average amount they were willing to pay was low. Knowledge of HPV, the HPV vaccine, cervical cancer, and income were factors associated with willingness to pay for the vaccine. Health workers were the primary source of information.

Social media HPV vaccination interventions show promise for increasing HPV vaccination rates. An important consideration for the implementation of effective interventions into real-world practice in the translation potential, or external validity, of the intervention. To this end, we conducted a systematic literature review to describe the current body of evidence regarding the external validity of social media HPV vaccination-related interventions. Constructs related to external validity were based on the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework. Seventeen articles published between 2006 and 2020 met inclusion criteria. Three researchers independently coded each article using a validated RE-AIM (reach, effectiveness/efficacy, adoption, implementation, maintenance) framework. Discrepant codes were discussed with a fourth reviewer to gain consensus. Of these 17 studies, three were pilot efficacy studies, 10 were RCTs to evaluate effectiveness, one was a population-based study, and three did not explicitly state which type of study was conducted. Reflecting this distribution of study types, across all studies the mean level of reporting RE-AIM dimensions varied with reach recording 90.8%, effectiveness (72.1%), adoption (40.3%), implementation (45.6%), and maintenance (26.5%). This review suggests that while the current HPV vaccination social media-driven interventions provide sufficient information on internal validity (reach and effectiveness), few have aimed to gather data on external validity needed to translate the interventions into real world implementation. Our data suggest that implementation research is needed to move HPV vaccination-related interventions into practice. Included in this review are recommendations for enhancing the design and reporting of these HPV vaccination social media-related interventions.

Objective: Despite increasing interest in understanding factors influencing awareness, knowledge, and acceptability of the human papilloma virus (HPV) vaccine among Latino parents to date, limited information is available specific to Latino fathers living in the United States. Methods: This descriptive qualitative study explored Latino fathers’ awareness, knowledge, and acceptability of the HPV vaccine for their adolescent children. Data were collected through individual, semi-structured interviews and analyzed using a hybrid method of thematic analysis that incorporated deductive and inductive approaches. Results: Nineteen, majority foreign-born Latino fathers (63.2%; n = 12) fathers of male and female adolescents participated in the study. Four main themes and two subthemes emerged from the analyses. Results found fathers’ low awareness and knowledge of HPV and the HPV vaccine. Results also identified fathers’ positive attitude toward vaccines in general. Moreover, results revealed fathers’ trust in healthcare providers. This trust translated into an increased willingness to vaccinate their children against HPV if recommended by their child’s primary healthcare provider. Conclusion: Findings indicate the need for increased efforts to raise awareness and knowledge among Latino fathers of HPV and the HPV vaccine. In addition, findings underscore the critical role of healthcare providers’ recommendation of the HPV vaccine. Given the limited research focused on Latino fathers, this study’s findings are valuable in building a knowledge foundation needed for developing future studies and interventions to promote the HPV vaccine by targeting Latino fathers living in the United States. Future research should quantify Latino fathers' awareness, knowledge, and acceptability of the HPV vaccine for their children, and preferences for educational interventions to promote HPV vaccination.

Background: Human papillomavirus (HPV) is diagnosed in most cervical cancers and is the fourth cause of cancer worldwide. Currently, fourteen HPV types are considered carcinogenic (HPV 16/18/31/33/35/39/45/51/52/56/58/59/66/68) with different oncogenicity. Cervical lesions might be due to HR (high risk)-HPV for what is important to identify new methods to genotype cervical lesions. The main goal was to identify, for the first time, HPV-HR in cervical lesions using Anyplex™ Detection kit in paraffin-embedded tissue. (2) Methods: It was performed a retrospective study in 45 women from Academic Hospital of Cova da Beira (CHUCB). DNA extraction was performed and through Anyplex™ II HPV-HR Detection kit HPV-HR were genotyped. (3) Results: HPV-HR were identified in 38 women; HPV-16 (55,26%), HPV-18/39/56/58/59 (5,26%), HPV-31 (21,05%), HPV-35 (7,89%), HPV-51/6 (2,63%) and HPV-52 (10,53%). (4) Conclusions: Our results reflect that Anyplex™ II HPV-HR Detection kit, designed for HR-HPV genotyping of cervical cancer screening, might be properly used to HR-HPV genotyping in histology. The proposed methodology allows an easy and cheaper technique that should be used as a future cervical risk stratification. It is a strong tool to be implemented in clinical practice in order to detect HR-HPV detection in cervical lesions, contributing to a more accurate diagnosis.

In Nigeria, Cervical cancer (CC) and lack of Human Papillomavirus (HPV) awareness poses significant HPV infection risk among women. This study was conducted at Ibrahim Badamasi Babangida (IBB) University in Nigeria; focused on assessing HPV awareness and knowledge, particularly concerning its association with CC and oral contraceptive (OC) pills among students and staff. We adapted and validated a 20-item HPV knowledge scale and explored factors influencing knowledge, vaccination rates, awareness, and the impact of ethnicity on HPV knowledge. Also, due to the non-normality of the knowledge score, non-parametric tests were done. Data were summarized using median and interquartile range (IQR), while categorical data were presented in frequency and percentage distribution. We established the reliability of the 20-item knowledge scale with a strong Cronbach's alpha coefficient of 0.913, indicating internal consistency. However, it revealed a concerning lack of awareness and knowledge about HPV, only 34.8% of participants were aware of HPV infection, and only 25.0% knew about HPV vaccine. Additionally, ethnicity was identified as a significant factor affecting HPV knowledge. Considering these findings, this study emphasizes the need for targeted interventions to enhance HPV awareness and knowledge, particularly among specific ethnic groups. Despite the development and validation of a reliable knowledge scale, the study underscores the importance of educational initiatives to address this knowledge gap, ultimately reducing the risk of HPV infection and CC in Nigeria.

Human papillomavirus (HPV) uses the cellular trafficking machinery to reach the cell nucleus and initiate a successful infection. The HPV capsid consists of two proteins: L1 (the major capsid protein) and L2 (minor capsid protein), and L2 is known to be responsible for trafficking the viral genome to the nucleus. From previous studies, we know that many cellular proteins interact with L2 and are involved in the trafficking process at different stages of the infectious entry process. To further investigate how HPV-16 achieves successful viral entry, we have performed a mass spectrometry analysis to identify novel interacting proteins that associate with incoming HPV-16 virions. We show that HPV-16 pseudovirions interact with a group of cellular cargo proteins (COPI), and here we confirm that this is mediated by the direct binding of L2, but not L1, to the COPB1 subunit. We also show that the ability of L2 to interact with COPB1 is conserved in both low- and high-risk HPV types. Furthermore, we also show that the interaction is essential for successful infection entry of multiple HPV types, thereby identifying a novel constituent of the infectious entry pathway of the HPV.

Cancer/testis (CT) antigens exhibit selective expression predominantly in immunoprivileged tissues in non-pathological contexts but are aberrantly expressed in diverse cancers. Because of their expression pattern, they have historically been attractive targets for immunotherapies. The investigation of mechanistic roles of CT antigens in promoting oncogenesis has historically been a prominent research question, and a growing number of studies implicate CT antigens in promoting almost all the hallmarks of cancer. This suggests that CT antigens may act as cancer drivers. CT antigens are expressed in head and neck squamous cell carcinomas, although their role in the pathogenesis, prognostication, and treatment for this family of cancers remains poorly studied. Given that CT antigens hold intriguing potential as therapeutic targets and as biomarkers for prognosis and therapeutic response and that they can provide novel insights into oncogenic mechanisms, their further study in the context of head and squamous cell carcinoma is warranted.

Persistent cervical infection with high-risk Human papillomaviruses (hrHPVs) is a necessary, but not sufficient, condition for the development of cervical cancer. Therefore, there are other co-factors facilitating the hrHPV carcinogenic process, one of which is smoking. In order to assess the effect of smoking on high-risk (hr) HPV DNA positivity and on the expression of HPV E7 oncoprotein, as a surrogate of persistent hrHPV infection, we used data from women recruited for the PIPAVIR project, which examined the role of E7 protein detection in cervical cancer screening. Women were tested for hrHPV DNA, using Multiplex Genotyping and E7 protein, using a novel sandwich ELISA method, and gave information on their smoking habits. Among 1473 women, hrHPV prevalence was 19.1%. The odds ratio (OR) for hrHPV positivity of smokers compared to non-smokers was 1.785 (95%CI: 1.365-2.332, p<0.001). The ORs for E7 positivity, concerning hrHPV positive women, ranged from 0.720 to 1.360 depending on the E7 detection assay used, but this was not statistically significant. Smoking increases the probability of hrHPV infection, and smoking intensity is positively associated to this increase. Smoking is not related to an increased probability of E7 protein positivity for hrHPV positive women.

Human papillomavirus (HPV) is associated with cellular changes of the cervix leading to cancer, which highlights the importance of vaccination in preventing HPV infections and subsequent cellular changes. Women undergoing treatment (LEEP) for high-grade cervical intraepithelial neoplasia (CIN2+) remain at risk for recurrence. This study assesses the effect of post-conization HPV vaccination on the viral status of women six months post-conization, aiming to evaluate the vaccine's effectiveness in preventing recurrence of CIN2+. A retrospective cohort study was conducted among women in Troms and Finnmark who underwent conization in 2022. Using the SymPathy database and the national vaccination register (SYSVAK), we analyzed the vaccination status and HPV test results of women born before 1991, who had not received the HPV vaccine prior to conization. Out of 419 women undergoing conization, 243 met the inclusion criteria. A significant association was found between post-conization HPV vaccination and a negative HPV test at six months follow-up (ARR = 12.1%, P = 0.039). Post-conization HPV vaccination significantly reduced the risk of a positive HPV test at the first follow-up, suggesting its potential in preventing recurrence of high-grade cellular changes. The retrospective design and the insufficient control of confounding variables underscore the necessity for further studies to confirm these findings.

Cervical cancer screening systems aim to detect established HPV infections early. However, if there are no high-grade lesions, the intervention choice is basically limited to observational follow-up with recommendations on life habits like diet, to favor infection control. Therefore, it is important to establish specific feeding guidelines that provide clear evidence about the benefit they may bring against HPV infections. The present study evaluates the benefits of nutritional supplementation with a casein hydrolysate-based formula in patients with HR-HPV infection, compared with a non-supplemented control group. A total of 118 patients completed 6 months of follow-up. Significant differences between supplemented and control groups were observed for total or partial HR-HPV clearance at 6 months (74.6% vs 35.6%). Supplemented patients also suffered a lower occurrence of new intracervical lesions (0% vs 28.6%), a significantly greater resolution (67.4% vs 41.9%) and less progression of pre-existing lesions (4.7% vs 9.7%) at 6 months. An increase in the effectors of cellular immunity that could be responsible for their effect was also observed in supplemented patients. We conclude that nutritional supplementation with this casein hydrolysate-based formula could improve the outcomes of observational management of HPV infection.

Human papillomavirus (HPV) can potentially compromise both unassisted conception and success rates with assisted reproductive technology (ART). We aimed to evaluate the rates of HPV vaccination among women presenting for fertility care. This was a prospective study analyzing a self-reported intake form completed by all new patients presenting to a fertility clinic. The primary outcome was HPV vaccination status. Among the 523 new patients included in this study 172 (32.9%) were fully vaccinated, 237 (45.3%) were unvaccinated, and 95 (18.2%) patients didn’t respond. There was a significant age difference between fully vaccinated patients (33.1 years) compared to unvaccinated patients (37.4 years) p&lt;0.001 and a significant difference in gravidity between fully vaccinated patients (average 0.65) and unvaccinated patients (average 1.11) p=0.0005. No significant association was found between HPV vaccination status and history of abnormal Pap smears or relationship status (single vs. married). Less than half of patients presenting to our fertility center were vaccinated against HPV, despite being eligible to receive the vaccine. Younger patients with lower gravidity were more likely to be vaccinated against HPV than older patients with higher gravidity. Reproductive Endocrinologists have the opportunity to recommend HPV vaccination for eligible patients presenting for fertility care.

Prostate cancer contributes to cancer-related deaths globally, and the etiology of this disease is not yet fully understood. While Human Papillomavirus (HPV) has been associated with several types of cancer, including cervical, anal, and oropharyngeal cancer, studies investigating the relationship between HPV and prostate cancer have shown mixed results. This systematic review aimed to evaluate the causative association between HPV and prostate cancer using Bradford Hill's criteria. A comprehensive search of PubMed was conducted, and 60 out of 482 studies were included in the review. The included studies were evaluated based on nine Bradford Hill criteria, and information on the identification and transmission of the virus and potential oncogenic mechanisms was also extracted. The strength of association criterion was not met, and other criteria, such as consistency and coherence, were not fulfilled. However, biological plausibility was supported, and potential oncogenic mechanisms were identified. While some studies have reported the presence of HPV in prostate cancer tissues, the overall quality of evidence remains low, and the association between HPV and prostate cancer is weak. Nevertheless, the prostate is a potential reservoir for the transmission of HPV, and the HPV E6 and E7 oncoproteins and inflammation are likely to be involved in any oncogenic mechanisms. Further studies with a higher level of evidence are needed to establish a definitive link between HPV and prostate cancer.

Human papillomavirus (HPV) infections, primarily transmitted through sexual contact, have been linked to various cancers, including cervical, penile, anal, oropharynx, breast, and prostate cancers. This study presents a unique case of concurrent high-risk HPV35, HPV45, and HPV59 infections in both prostate and bladder cancer tissues from a single patient, representing the first documented instance worldwide with identical HPV types detected in two adjacent organs of the same individual. Employing a multiplex-PCR approach, gel electrophoresis, and Sanger sequencing, we confirmed the presence of these high-risk HPV types. Additionally, Western blot analysis using an HPV E7 antibody demonstrated the active expression of HPV oncoproteins in both cancer types. This discovery underscores the potential for HPV intra-organ transmission and necessitates further exploration of alternative transmission routes. The implications of our results offer new insights into the complex dynamics of HPV transmission in cancer pathogenesis.

Cervical cancer is preventable through vaccination, early detection, and treatment of precancerous lesions. However, global inequalities mean that the disease remains a leading cause of cancer death around the world, with over 80% of new cases and 90% of deaths occurring in low and middle-income countries (LMICs). In El Salvador, joint efforts between the Ministry of Health (MoH) and the non-profit organization Basic Health International (BHI) have been in place since 2008 with the goal of reducing the country’s disease burden. While the World Health Organization’s (WHO) call to action to eliminate cervical cancer provided worldwide momentum to implement new public health initiatives, the COVID-19 pandemic disrupted ongoing programs and jeopardized plans for the future. The purpose of this manuscript is to describe the progress that El Salvador has achieved in improving cervical cancer prevention, the impact of the pandemic on current strategies, and potential solutions that can help the country meet the WHO’s strategic targets by 2030 to accelerate the elimination of cervical cancer.

Human papillomavirus (HPV) infection is a widespread sexually transmitted infection linked to various types of cancers. Although vaccination against HPV is available, global HPV vaccination rates remain low. This study aimed to evaluate the awareness and knowledge of the HPV vaccine and to identify predictors associated with vaccine hesitancy among health college students in Saudi Arabia. A cross-sectional survey was distributed to students enrolled in health colleges. The association of vaccine hesitancy with sociodemographic characteristics was examined using logistic regression analysis. The study found that approximately half of the students (49.9%) were aware of the HPV vaccine. Students from the College of Medicine showed the highest level of knowledge. Only a small proportion (5.2%) reported receiving the vaccine. The overall HPV vaccine hesitancy was 59.1% (43.9% for women and 75.9% for men). The most common reasons for vaccine hesitancy was not knowing enough about it. Men were twice as likely as women to believe that they did not need the HPV vaccine. The odds for HPV vaccine hesitancy were greater among men and younger age group compared to women and older age group. In conclusion, the study underscores the importance of awareness campaigns on HPV vaccination, targeting primarily male students.

The oncogenic potential of high-risk HPVs is focused on producing the E6 and E7 oncoproteins responsible for disrupting the control of the cell cycle. Epidemiological studies propose the presence of the N29S and H51N variants of the HPV16 E7 protein as a significant association with cervical cancer. It has been suggested that changes in the amino acid sequence of E7 variants may affect the oncoprotein 3D structure; however, this remains unknown. Analysis of the structural differences of the HPV16 E7 protein and its variants (N29S and H51N) was performed through homology modeling and structural refinement by molecular dynamics simulation. We propose for the first time a 3D structure of the E7 reference protein and two of its variants (N29S and H51N) and conclude that the mutations induced by the variants in N29S and H51N have a significant influence on the 3D structure of the E7 protein of HPV16, which could be related to the oncogenic capacity of this protein.

It has been shown that Human papillomavirus (HPV) infection is associated with several forms of cancer. Additionally, although there are more than 100 types of HPV, more than ten types of it, including types 16 and 18, are considered high-risk. The two proteins that make up the viral capsid of HPV 16 are L1, the major capsid protein, and L2, the minor capsid protein. FDA (The Food and Drug Administration) approved HPV vaccines mostly target L1 and L2 capsid proteins, which facilitate intracellular entry during infection. In this study, it was set out to analyze the creation of phylogenetic relations of L1 nucleic acid sequences of viral isolates. This study also analyzed sequences of three key elements within the amino acid sequences of HPV 16 L1: loops critical for structural stability, nuclear localization signal sequences, and residues implicated in viral attachment. As highlighted by the literature, these elements represent pivotal aspects of viral function. Furthermore, the report highlighted the particular inter-sequence variability within the HPV 16 L1 protein sequences. Overall analysis revealed clustering of sequences primarily due to geographical and characterized by more phylogenetic relatedness within location-specific clusters.

Cervical cancer presents a significant global health concern with high-risk human papilloma-viruses (HPVs) being identified as the cause of this cancer. Although current treatment methods for cervical cancer can eliminate lesions, preventing metastatic spread and minimizing tissue damage remains a major challenge. Therefore, the development of a safer and innovative thera-peutic approach is of utmost importance. Natural products like Fig latex, derived from the Ficus Carica tree, have demonstrated promising anti-cancer properties when tested on cervical cancer cell lines. However, the specific mechanisms by which Fig latex exerts its effects are still un-known. In this study, we conducted RNA-seq analysis to explore how Fig latex may counteract carcinogenesis in HPV-positive cervical cancer cell lines, namely CaSki (HPV type 16-positive) and HeLa (HPV type 18-positive). Our data from this investigation indicates that Fig latex influ-ences the expression of genes associated with the development and progression of cervical can-cer, including pathways related to " Nonsense-Mediated Decay (NMD) "cell cycle regulation" and Transcriptional Regulation by TP53. This selective impact of Fig latex on cancer-related pathways suggests a potential novel therapeutic approach for HPV-related cervical cancer.

Background and Objectives: Romania ranks among the countries with a notably high rate of preventable deaths due to inadequacies in prevention, screening, early detection, and timely management processes. Cervical cancer (CC) is a significant contributor to these preventable deaths, particularly affecting patients from marginalized backgrounds, rural regions, and the Roma population. The purpose of this article was to identify correct and consistent information of the Roma population about the risk of CC, as well as the importance of understanding the causes of the disease and awareness of the available prevention methods. Materials and methods: A cross-sectional study was conducted using a self-administered questionnaire applied only to Roma women in Romania. Results: We enrolled 759 patients in the study. These were divided into 2 groups, Group 1 comprised 289 (38.1%) women who had been tested for HPV infection, while Group 2 included 470 (61.9%) women who had never been tested for HPV infection. Characterization of women in Group 1: mostly aged between 25-54 years, with high school education, married, who started sexual activity under the age of 18 years, with only one sexual partner and with over 5 pregnancies. Regarding contraceptive methods, 35.7% of women do not know/ use any contraceptive method, and 32.2% use hormonal contraceptives. Two thirds of the women tested had heard of HPV, and 19.7% were vaccinated against HPV with at least 2-3 doses. A percentage of 8.7 had a diagnosis of CC, compared to those who were not tested (p-0.0001), whereas 63% of the tested women do not know much about CC, as opposed to 85.7% of the group of untested women. Conclusion: Cervical cancer (CC) continues to be a public health issue in Romania, particularly in patients belonging to vulnerable groups. Promotion campaigns for HPV vaccination and CC screening are necessary to reduce the associated mortality and morbidity.

Pervasive purifying selection on non-synonymous substitutions is a hallmark of papillomavirus genome history. Whereas the role of selection on, and drift of, non-coding DNA elements on HPV diversification is poorly understood. More than a thousand complete genomes representing Alphapapillomavirus types, lineages and SNP variants were examined phylogenetically and interrogated for the number and position of non-coding DNA sequence motifs using Principal Components Analyses, Ancestral State Reconstructions and Phylogenetic Independent Contrasts. For anciently diverged Alphapapillomavirus types, composition of the 4 nucleotides (A,C,G,T), codon usage, trimer usage and 13 established non-coding DNA sequence motifs revealed phylogenetic clusters consistent with genetic drift. Ancestral state reconstruction and Phylogenetic Independent Contrasts revealed ancient genome alterations, particularly for CpG and APOBEC3 motifs. Each evolutionary analytical method we performed supports the unanticipated conclusion that genetic drift and different evolutionary drivers have structured Alphapapillomavirus genomes in distinct ways during successive epochs, even extending to differences in more recently formed variant lineages

In sub-Saharan Africa (SSA), cervical cancer is a critical public health issue; it is the second leading cause of cancer among women and the leading cause of female cancer deaths. Incidence and mortality rates are substantially higher than in high-income countries with population-based screening programs, yet implementing screening programs in SSA has so far proven to be challenging due to financial, logistical and sociocultural factors. Human Papillomavirus (HPV) vaccination is an effective approach for primary prevention of cervical cancer and presents an opportunity to reduce the burden from cervical cancer in SSA. With a number of SSA countries now eligible for GAVI support for vaccine introduction, it is timely to consider the factors that impede and facilitate implementation of vaccine programs in SSA. This article reviews the epidemiological and clinical features of cervical cancer in SSA and describes the current status of HPV vaccine implementation in SSA countries. The review considers the challenges that will need to be addressed, and effective approaches to the design and implementation of HPV vaccination programs, using Rwanda as a case study. The review aims to provide suggestions and guidance to those involved in the development and implementation of HPV vaccination programs in SSA.

Background: Human papillomavirus (HPV) infection plays a key role in the development of cervical cancer that ranks as the third most common gynecological cancer in China. We attempt to investigate the age and genotype-specific prevalence of HPV DNA in western Chinese females. Methods: A total of 301,880 woman were recruited from 4 different regions of western China. Routine cervical samples were collected and HPV screening was performed using 21 HPV Genotyping test (Hybribio). The overall prevalence, age-specific prevalence, and genotype distribution were analyzed. Results: The overall prevalence of HPV was 18.01%. The high-risk HPV infection rate was 79.14%, the low-risk HPV infection rate was 12.56%, and the mixed HPV infection rate was 8.30%. The most common 4 HR HPV subtypes were HPV-52, 16, 58 and 53, which accounted for 20.49 %, 19.93 %, 14.54 % and 10.01 %. In LR HPV genotype, HPV-6 ranked the highest (28.17 %), followed by HPV-81 (9.09 %), HPV-11 (3.78 %). HPV genotype subgroup analysis also showed that single-type infections had the highest prevalence rate (77.26%) among HPV positive individuals. Among muti-infection genotype, double infection was most common with frequencies of 76.04%. Conclusion: This large report shows that the overall prevalence of HPV was high in China, whose distribution exhibits different patterns across different particular age and regions. Viral genotypes HPV53, 6 were are frequently detected in this population, which is worth of significant clinical attention.

Background: Understanding the distribution of HPV types in cervical cancer cases is crucial for evaluating the effectiveness of HPV screening and vaccination in reducing cervical cancer burden. This study aimed to assess genotype prevalence among 178 cervical cancer cases detected during a 20-year screening period in Northern Norway and compare the potential efficacy of HPV vaccines in preventing cervical cancer. Methods: A total of 181 formalin-fixed paraffin-embedded (FFPE) tissue samples from women diagnosed with cervical cancer between 1995 and 2015 in Troms and Finnmark, Norway, were analyzed using a 45-type HPV DNA test. The results were compared to a 7-type HPV mRNA test targeting oncogenic types included in the nonavalent HPV vaccine. Results: Invalid HPV test results were observed in 1.7% (3/181) of the samples and were subsequently excluded from further analysis. Among the remaining cases, 92.7% (165/178) tested positive for HPV using any test combination. HPV DNA was detected in 159 cases (89.3%), while HPV mRNA was detected in 149 cases (83.7%). The most prevalent HPV types were 16 and 18, responsible for 70.8% of the cases, with the nonavalent vaccine types accounting for 86.6% of cases. HPV 35 was identified in eight cases (4.5%). Conclusion: The bivalent/quadrivalent HPV vaccines have the potential to prevent 76.4% (126/165) of HPV-positive cervical cancer cases, while the nonavalent vaccine could prevent 93.3% (154/165) of cases. Tailoring screening strategies to target HPV types with the highest oncogenic potential may improve cervical cancer detection and enable targeted interventions for high-risk individuals. The use of a 7-type HPV mRNA test holds promises as an advantageous approach.

The incidence and mortality rates of cervical cancer are rising among young women in Japan. In November 2021, the Japanese Ministry of Health, Labour and Welfare reinstated the active recommendation for the human papillomavirus (HPV) vaccine, which was discontinued in June 2013 due to reports of adverse reactions, including chronic pain and motor dysfunction, following vaccination. However, vaccine hesitancy among the younger generation remains, and it is essential to identify the barriers in vaccination uptake. Therefore, we aim to conduct a randomized study using different methods of providing educational contents to improve health literacy regarding cervical cancer and HPV vaccination among female students in Japan. Here, we present the results of our preliminary report and discuss current topics related to HPV vaccination in Japan. Data were collected from 27 female students—divided into three groups: no intervention, print-based intervention, and SNS-based intervention—using the Health Literacy Scale and Communicative and Critical Health Literacy scale. Our primary results indicate that participants’ knowledge and health literacy improved post intervention. Therefore, medical professionals must provide accurate scientific knowledge regarding routine HPV vaccination and the risk of cervical cancer to young women to improve their health literacy and subsequently increase the HPV vaccination rates.

The incidence of human papillomavirus-related head and neck squamous cell carcinoma (HPV+HNSCC) has reached epidemic levels in the last decade. While prophylactic vaccines will prevent future HPV infections, there are currently no HPV-specific antiviral drugs to treat current HPV infections or HPV+HNSCC. HPV replication and transcription are promising targets for anti-HPV therapeutics, as modulation of these processes can alter expression levels of HPV E6 and E7, which are required for maintenance of the transformed phenotype. This is a particularly attractive target in in HPV+HNSCC where the majority of tumors have episomal genomes replicating in an E1-E2 dependent manner. Here, we describe a model system to study HPV16 E1-E2 mediated DNA replication and HPV16 E2-mediated transcriptional activation and repression in multiple HNSCC cell lines. Our results demonstrate that low levels of IFIT1 are required for HPV16 replication in HNSCC cell lines and HPV16 E1 interacts with IFIT1. Restoration of IFIT1 expression in HNSCC cell lines partially inhibits HPV16 E1-E2 mediated replication. This system can be used to study replication and transcription by HPV16 E1 and E2 in HNSCC as well as be utilized to screen potential anti-HPV therapeutics that target HPV16 replication and transcription.

Background: Telomere length (TL) shortening process is associated with several known environment and individual determinants. DNA methylation is the most studied epigenetic process and may be associated with TL. We investigated the associations between DNA methylation and TL in peripheral blood. Methods: Methylation wide association study was conducted in 47 women (37.1±8.8 years) with different nutritional status. Association between TL and DNA methylation levels were explored by univariate and multiple linear regression models, corrected by age and Body Mass Index. Corrections for multiple comparisons by Benjamini‐Hochberg test was also performed. WEBGestalt was used to identify pathways that are responsible for regulating TL. Results: We found negative correlations between TL and BMI (r = -0.641; p = 0.001), abdominal circumference (r = -0.622; p = 0.001) and fat mass (r = -0.656; p = 0.001). 44 CpGs sites were associated with TL, independent of age and BMI. The most of these sites were negatively correlated with TL. For the 7 remained sites, DNA hypomethylation were associated with shorter TL. These CpGs were related to nine different pathways, including thermogenesis, cancer, glutamatergic and serotonergic synapse. Conclusion: There is an epigenetic contribution in TL, independent of nutritional status and age. Genes related to TL are involved in important metabolic pathways.

Replication protein A (RPA) is a heterotrimeric protein complex and the main single-stranded DNA (ssDNA) binding protein in eukaryotes. RPA has key functions in most of the DNA-associated metabolic pathways and DNA damage signalling. Its high affinity for ssDNA helps to stabilise ssDNA structures and prevents the DNA sequence from nuclease attacks. RPA consists of multiple DNA-binding domains which are oligonucleotide/oligosaccharide-binding (OB)-folds, responsible for DNA binding, and interactions with proteins. These RPA-ssDNA and RPA-protein interactions are crucial for DNA replication, DNA repair, DNA damage signalling, and the conversation of the genetic information of cells. Proteins such as ATR use RPA to locate to regions of DNA damage for DNA damage signalling. Recruitment of nucleases and DNA exchange factors to sites of double strand breaks are also an important RPA function to ensure effective DNA recombination to correct these DNA lesions. Due to its high affinity to ssDNA, RPA’s removal from ssDNA is of central importance to allow these metabolic pathway to proceed and processes to exchange RPA against downstream factors are established in all eukaryotes. These facetted and multi-layered functions of RPA will be discussed in detail in the review. RPA is also a major player in a variety of human diseases, which will be discussed.

OBJECTIVE: Cervical cancer is a major cause of cancer-related mortality, necessitating effective screening and diagnostic methods. This study aimed to assess the performance of cervicovaginal smear (CVS) and Human papilloma virus (HPV)-DNA cotest. STUDY DESIGN: The pathology results of 225 female patients who underwent HPV-DNA testing with CVS between 2014 and 2022 and were subsequently diagnosed by colposcopic cervical biopsy or second CVS were retrospectively analyzed. RESULTS: CVS samples showed Atypical Squamous Cells of Undetermined Significance (ASCUS), Low-grade squamous intraepithelial lesion (LSIL), High-grade squamous intraepithelial lesion (HSIL) and cervical cancer. Concordance between the first and second diagnoses demonstrated moderate agreement for LSIL. ASCUS cases exhibited a significant correlation with HPV-DNA positivity and higher-grade cervical lesions. In biopsy, sensitivity and specificity for CIN 2 were 67.8% and 67.9%, respectively, while for CIN 3, they were 81.8% and 58.5%. HPV testing showed significant correlation with histopathologic results. In women over 40 years, more intraepithelial lesions were diagnosed compared to younger women (p<0.005). The conventional smear technique proved reliable in detecting high-grade lesions. CONCLUSION: Despite the limitations of our study, our results emphasize the value of HPV-DNA testing to avoid unnecessary interventions and to establish appropriate follow-up strategies.

Recurrent respiratory papillomatosis (RRP) is a non- malignant disease, characterized by the production of wart-like growths in respiratory tract, affecting both young and adults (Juvenile-Onset Recurrent Respiratory Papillomatosis, JORRP and Adult-Onset Recurrent Respiratory Papillomatosis, AORRP, respectively). Infection caused by Human Papillomavirus (HPV) is known as the main factors involved in RRP development. Complications of RRP may rarely occur, including lung involvement and malignant transformation. The present systematic review was aimed to evaluate the prevalence of severe complications, as lung involvement and lung tumor in JORRP and AORRP patients, following the guideline for reporting systematic reviews and meta-analysis (PRISMA Statement). Among the 378 studies were found on PubMed and Scopus using the following MESH terms “recurrent respiratory papillomatosis and lung tumor” and “pulmonary tumor and recurrent respiratory papillomatosis”. Basing on inclusion and exclusion criteria, a total of 11 studies were included in the systematic review. We found a pooled prevalence of 8% (95% CI:4%-14%; I2: 87.5%) for lung involvement in RRP patients. In addition, we found a pooled risk difference of 5% in lung involvement between JORRP and AORRP (95% CI: -7%-18%; I2 :85.6%, p-value: 0.41). Among patients with lung involvement, we observed a pooled prevalence of lung tumor of 4% (95% CI:1%- 7%; I2: 67.1%), and a pooled prevalence mortality for this group of 4% (95% CI:2%-6%; I2: 0%). Overall, the positivity rate for HPV-6 and -11 in patients with RRP was 91%. Considering only cases with pulmonary involvement, the pooled prevalence for HPV 11 was 21% (95% CI: 5%-45%; I2: 77.2%). Our results evidenced a low/middle risk of pulmonary involvement and lung tumor in JORRP and AORRP patients, with an increased risk for HPV-11 positive patients. Further studies should be performed to improve knowledge and adopt preventive measures to contrast the progression to severe diseases in RRP patients.

Background: Human papillomavirus is a common pathogen that infects the skin and mucosal epithelium, is transmitted sexually; causes condylomas or squamous cell carcinomas. Two (16 and 18) of the 150 HPV serotypes are oncogenic types. Studies have been done on the infection by oncogenic human papillomavirus 16/18 and associated factors are found to be very limited in Ethiopia. Objective: This study aimed to assess the prevalence of oncogenic human papillomavirus infection (HPV 16/18) and associated factors among women. Methods: An institutional-based cross-sectional study was conducted among 337 women screened for cervical cancer in two hospitals in East Gojjam Zone from February to April 2021 G.C. Four BSc-qualified nurses who worked in the chosen hospitals collected the data using pretested questionnaire and an HPV test (OncoE6TM Cervical Test) specific to HPV16/18 in cervical swabs. Descriptive analysis was performed to determine the prevalence and a multivariate logistic regression model was used to identify the associated factors of HPV16/18 infection. Finally, statistical significance was declared at P < 0.05.Results: The prevalence of HPV infection was 14.2% (95% CI: 10.7% -18.1%). The mean age of the respondents was 36.7±9.1 years. Women with the age group of 55-65 years (AOR = 7.91, 95% CI: 1.95-32.09), early initiation of sexual intercourse (AOR = 5.36, 95% CI: 1.58-18.13), history of sexually transmitted infection (STI) (AOR = 3.52, 95% CI: 1.27-9.72), human immunodeficiency virus (HIV) positive status (AOR = 6.8, 95% CI: 1.99-23.54), and number of lifetime sexual partners (AOR = 4.37, 95% CI: 1.15-17.3) were important independent factors associated with the presence of oncogenic HPV infection. Conclusion and Recommendation: We found a relatively low prevalence of high-risk HPV infection. Age, early initiation of sexual intercourse at less than 18 years, STI of women, being HIV seropositive, and a number of sexual partners were important factors for high-risk HPV infection. Women aged > 46 years, women with early initiation of sex, a history of STI, being HIV positive, and a history of multiple sexual partners should be encouraged to be screened and vaccinated for HPV infection. Wider-ranging studies are also needed in HPV-infected women in association with the cervical lesion.

According to cancer death rates for women worldwide, this form of cancer ranks fourth after breast, bronchopulmonary, and colorectal cancer, affecting around 570,000 women annually. About 270,000 women each year pass away from this illness, 85% of them are from underdeveloped nations where cervical cancer claims more lives than any other kind of cancer. In Romania, cervical cancer ranks fourth in terms of death, behind breast, bronchopulmonary, and colorectal cancers, and second in terms of incidence, behind breast cancer. Endometriosis in the cervical region is quite uncommon. Only a tiny fraction of women had the condition upon diagnosis. It might be challenging to detect cervical endometriosis since it rarely manifests any symptoms or markers. Women who are asymptomatic can manage the condition expectantly; however, if the symptoms return often, surgery may be required. As many patients have concurrent diseases such fibroids, adenomyosis, ovarian cysts, and pelvic endometriosis, cervical endometriosis therapy appears to be straightforward. There ought to be surgical intervention. Symptomatic cervical endometriosis, such as irregular or post-coital bleeding, may be treated surgically using the LLETZ surgery or another cervical ablation approach. Background and Objectives: (1) To assess one's degree of knowledge on the signs, causes, and methods of preventing cervical cancer or cervical endometriosis, as well as screening for these conditions. (2) To ascertain how the responder behaves about cervical cancer screening and prevention, as well as endometriosis in the cervical region. Materials and Methods: A case report about cervical cancer or cervical endometriosis was conducted among a patient from Romania, Timisoara. Results: In this study, we report the patient with cervical endometriosis, although he was initially diagnosed with cervical cancer. Conclusions: Cervical cancer, a condition that can have serious repercussions on the patient's health, even if there is no clear picture of paraclinical investigations, to raise the suspicion of cervical endometriosis and not cervical cancer.

Background: Sinonasal squamous cell carcinoma (SNSCC) is rare in the general population. No clear and consistent etiologic correlation between human papillomavirus and SNSCC has yet been delineated in literature. p16 is a tumour suppressor protein used as a surrogate marker for HPV. This study aims to evaluate the relationship between p16 overexpression in SNSCC and its role in prognosis and survival. Methods: A population-based retrospective analysis was performed using prospectively collected data from the Northern Alberta Head and Neck Tumour Board, Alberta Cancer Registry, and Alberta Cancer Research Biobank. p16 overexpression was analyzed from pathologic sample of patients meeting study criteria, and participants were dichotomized by status. Subsequently, nonparametric analysis of demographics, initial staging, and initial treatment were performed, and a Kapan-Meier curve was developed to assess differences in survival. Results: 16 patients were included in analysis. p16 overexpression was seen in 68.8% of patients. p16 positive and negative groups were comparable for age, gender, smoking status, stage, and treatment. A statistically significant five-year survival advantage was observed in patients with p16 positive SNSCC (p = 0.013). Conclusions: This is the first Canadian study to demonstrate a high prevalence of p16 positivity in SNSCC and its presence denoting a statistically significant survival advantage. Results demonstrate a previously unconfirmed role of oncogenic HPV in SNSCC.

Human papillomavirus (HPV) self-sampling (Self-HPV) is a promising strategy to improve cervical cancer screening coverage in low-income countries. However, issues associated with women who prefer conventional HPV clinical-sampling over HPV self-sampling may affect screening participation. To address this issue, our study assessed factors associated with women’s preferences related to Self-HPV. This study was embedded in a large clinical trial recruiting women aged 30–49 years in a primary HPV-based study termed “3T-Approach” (for Test-Triage-Treatment), launched in 2018 at Dschang District Hospital, West Cameroon. Participants were invited to perform a Self-HPV. After the sampling and before receiving the results, participants completed a questionnaire about cervical cancer screening and their preferences and perceptions around Self-HPV. The median age of the 2201 participants was 40.6 (IQR 35–45) years. Most (1693 (76.9%)) preferred HPV self-sampling or had no preference for either method and 508 (23.1%) preferred clinician-sampling. Factors associated with an increased likelihood of reporting a clinician-sampling preference were tertiary educational level (14.4% CI: 12.8–16.1 vs 29.5% CI: 25.6–33.6) and being an employee with higher grade professional or managerial occupations (5.5% CI: 3.8–7.9 vs 2.6% CI: 2.3–2.8). The main reported reason for women preferring clinician-sampling was a lack of “self-expertise”. Most women (&gt;99%) would agree to repeat HPV self-sampling and would recommend it to their relatives. HPV self-sampling in the cultural context of central Africa was well accepted by participants, but some participants would prefer to undergo clinician sampling. Health systems should support well-educated women to increase self-confidence in using HPV self-sampling.

Track-structure Monte Carlo simulations are useful tools to evaluate initial DNA damage induced by irradiation. In the previous study, we have developed a Gean4-DNA-based application to estimate the cell surviving fraction of V79 cells after irradiation, bridging the gap between the initial DNA damage and the DNA-rejoining kinetics by means of the two-lesion kinetics (TLK) model. However, since the DNA repair performance depends on cell line, the same model parameters cannot be used for the different cell lines. Thus, we extended the Geant4-DNA application with an updated TLK model for the evaluation of DNA damage repair performance in HSGc-C5 carcinoma cells which are typically used for evaluating proton/carbon radiation treatment effects. For this evaluation, we also performed experimental measurements for cell surviving fractions and DNA-rejoining kinetics of the HSGc-C5s cells. Concerning fast- and slow-DNA rejoining, the TLK model parameters were adequately optimized with the simulated initial DNA damage. Using the optimized TLK model, the Geant4-DNA simulation is now able to predict cell survival and DNA-rejoining kinetics for HSGc-C5s cells.

Cancer-associated fibroblasts (CAF) form the basis of tumor microenvironment and possess immunomodulatory functions by interacting with other cells surrounding tumor, including T lymphocytes, macrophages, dendritic cells and natural killer cells. Ionizing radiation is a broadly-used method in radiotherapy to target tumors. In mammalian cells, ionizing radiation induces various types of DNA damages and DNA damage response. Being unspecific, radiotherapy affects all the cells in tumor microenvironment, including the tumor itself, CAFs and immune cells. CAFs are extremely radio-resistant and do not initiate apoptosis even at high doses of radiation. However, following radiation, CAFs become senescent and produce a distinct combination of immunoregulatory molecules. Radiosensitivity of immune cells varies depending on the cell type due to inefficient DNA repair in, for example, monocytes and granulocytes. In this minireview, we are summarizing recent findings on the interaction between CAF, ionizing radiation and immune cells in the tumor microenvironment.

Covalent DNA protein crosslinks (DPCs) are common lesions that block replication. We examine here the consequence of DPCs on mutagenesis involving replicational template-switch reactions in Escherichia coli. 5-azacytidine (5azaC) is a potent mutagen for template-switching, dependent on DNA cytosine methylase (Dcm), implicating the trapped Dcm-DNA covalent complex as the initiator for mutagenesis. The leading strand of replication is more mutable than the lagging strand, explained by blocks to the replicative helicase and/or fork regression. We find that template-switch mutagenesis induced by 5-azaC does not require DSB repair via RecABCD. The ability to induce the SOS response is anti-mutagenic by an unknown mechanism. Mutants in recB, but not recA, exhibit high constitutive rates of template-switching and we suggest that RecBCD-mediated DNA degradation prevents template-switching associated with fork regression. A mutation in the DnaB fork helicase also promotes high levels of template-switching. We also find that other DPC-inducers, formaldehyde (a non-specific crosslinker) and ciprofloxacin (a topoisomerase II poison) are also strong mutagens for template-switching. Induction of mutations and genetic rearrangements that occur by template-switching may constitute a previously unrecognized component of the genotoxicity and genetic instability promoted by DPCs.

It is well known that X-ray crystallography is based on X-ray diffraction (XRD) by atoms and molecules. The diffraction pattern arises as a result of scattering of incident radiation, which makes it possible to determine the structure of the scattering substance. With the advent of ultrashort radiation sources, the theory and interpretation of X-ray diffraction analysis remained the same. This work shows that when an attosecond laser pulse is scattered on a DNA molecule, including during its nicking and bending, the pulse duration is an important characteristic of the scattering. In this case, the diffraction pattern changes significantly compared to the previously known scattering theory. The results obtained must be used in XRD theory to study DNA structures, their mutations and damage, since the previously known theory can produce large errors and, therefore, the DNA structure can be “deciphered” incorrectly.

DNA methylation is an epigenetic mechanism for gene expression modulation and can be used as a predictor of future disease risks. A prospective birth cohort study was performed to clarify the effects of neurotoxicants on child development, namely, the Tohoku Study of Child Development, in Japan. This study aimed to evaluate the association of prenatal exposure to five toxic metals—arsenic, cadmium, mercury, lead (Pb), antimony (Sb), and polychlorinated biphenyls (PCBs, N = 166)—with global DNA methylation in umbilical cord blood DNA. DNA methylation markers, 5-methyl-2’-deoxycytidine (mC) and 5-hydroxymethyl-2’-deoxycytidine (hmC), were determined using liquid chromatography-tandem mass spectrometry. The mC content in cord blood DNA was positively correlated with Pb and Sb levels (r = 0.442 and 0.288, respectively) but not with cord blood PCBs. We also observed significant positive correlations among Pb levels, maternal age, and hmC content (r = 0.159 and 0.243, respectively). The multiple regression analysis among the potential predictors demonstrated consistent positive associations between Pb and Sb levels and mC and hmC content. Our results suggest that global DNA methylation is a promising biomarker for prenatal exposure to Pb and Sb.

Abstract5′,8-Cyclo-2′-deoxyadenosine (cdA), in the 5′R and 5′Sdiastereomeric forms, are typical non strand-break oxidative DNA lesions, induced by hydroxyl radicals, with emerging importance as a molecular marker. These lesions are exclusively repaired by nucleotide excision repair (NER) mechanism with a low efficiency, thus readily accumulating in the genome. Poly(ADP-ribose) polymerase1 (PARP1) acts as an early responder to DNA damage and plays a key role as a nick sensor in the maintenance of the integrity of the genome by recognizing nicked DNA. So far, it was unknown whether the diastereomeric cdA lesions could induce specific PARP1 binding. Here we provide the first evidence of PARP1 to selectively recognize the diastereomeric lesions 5′S-cdA and 5′R-cdA in vitro as compared to deoxyadenosine in model DNA substrates (23-mers) by using circular dichroism,fluorescence spectroscopy, immunoblotting analysis and gel mobility shift assay. Several features of the recognition of the damaged and undamaged oligonucleotides by PARP1were characterized. Remarkably, PARP1 efficiently binds to both cdA lesions in the double stranded (ds)-oligonucleotides. In particular, PARP1 proved to bind 5′S-cdAwith a higher affinity constant for the 5'S lesion in a model of ds DNA than 5′R-cdA, showing different recognition patterns, also compared with undamaged dA. This new finding highlights the ability of PARP1 to recognize and differentiate the distorted DNA backbone in a biomimetic system caused by different diastereomeric forms of a cdA lesion.

Recent advances in DNA sequencing technology have shown that the human milk microbiota of healthy women varies substantially. The gDNA extraction method may influence the observed variation, biasing the microbiological reconstruction after all. In this study, a genomic DNA extraction method for DNA isolation from human milk samples was standardized and compared with commercial and standard hose make methods. Spectrophotometric measurements, gel electrophoresis, and PCR amplifications were used as criteria for evaluating the quantity, quality, and functionality of the extracted DNA. Furthermore, the standardized method of extracting gDNA from human milk was evaluated for its ability to isolate functional DNA from gram-positive, and gram-negative bacteria and fungi, to improve the reconstruction of microbiological profiles. The novel DNA extraction method increased the quantity and quality of the gDNA extracted compared with commercial and standard house-make protocols. This method even allowed PCR amplification of the V3-V4 regions of the 16S ribosomal gene in all samples, and the ITS-1 region of the fungal 18S ribosomal gene in 95 % of the samples as well. It is concluded that the proposed method provides better performance for the extraction of gDNA from complex samples such as human milk.

DNA methylation, one of the major epigenetic mechanisms, plays critical roles in regulating gene expression, genomic stability and cell lineage commitment. Establishment and maintenance of DNA methylation in mammals is achieved by two groups of DNA methyltransferases: DNMT3A and DNMT3B, which are responsible for installing DNA methylation patterns during gametogenesis and early embryogenesis, and DNMT1, which is essential for propagating DNA methylation patterns during replication. Both groups of DNMTs are multi-modular proteins, containing a large N-terminal regulatory region in addition to the C-terminal methyltransferase domain. Recent structure-function investigations of the individual domains or large fragments of DNMT1 and DNMT3A have revealed the molecular basis for their substrate recognition and specificity, intramolecular domain-domain interactions, as well as their crosstalk with other epigenetic mechanisms. These studies highlight a multifaceted regulation for both DNMT1 and DNMT3A/3B, which is essential for the precise establishment and maintenance of lineage-specific DNA methylation patterns in cells. This review summarizes current understanding of the structure and mechanism of DNMT1- and DNMT3A-mediated DNA methylation, with emphasis on the functional cooperation between the methyltransferase and regulatory domains.

Background: Human Papillomavirus causes various types of cancer in both men and women. Woman with HPV infection has a risk of developing invasive cervical cancer. Globally, HPV 16 and 18 were predominant. This study aims to find the distribution of various HPV types in South Andaman. Methods: A cross sectional study conducted among woman in South Andaman where cervical scrapes were collected after the collecting the written informed consent. Detection of HPV genotypes was carried out by using PCR assay. Further, sequencing analysis was performed using MEGA11 to identify various genotypes in this territory. Result: Of these 1000 samples, 32 were positive for HR-HPV16 and 4 were positive for HR-HPV18. Fifteen HPV genotypes were detected using molecular evolutionary analysis. Six cases were identified with multiple genotypes. Most prevalent genotype is HPV16 which belonged to Lineage-A and sub-lineage A2. HPV18 identified in South Andaman belonged to the lineage A1 to A5. Discussion: Various HPV types were identified among women in South Andaman. Global burden of cervical cancer associated with various HPV sub-lineages. HPV-16 A1 sub-lineage was globally widespread whereas sub-lineages A1, A2 and D1 was prevailing in South Andaman. Conclusion: High risk HPV identified in this study enlightening the importance of HPV vaccination among the woman in remote places. These findings will help to strengthen public health awareness programs and prevention strategies for the women in remote areas.

In most industrialized countries, screening programs for cervical cancer have shifted from cytology (Pap smear or ThinPrep) alone on clinician-obtained samples to the addition of screening for human papillomavirus (HPV), its main causative agent. For HPV testing, self-sampling instead of clinician-sampling has proven to be equally accurate, in particular for assays that use nucleic acid amplification techniques. In addition, HPV testing of self-collected samples in combination with a follow-up Pap smear in case of a positive result is more effective in detecting precancerous lesions than a Pap smear alone. Self-sampling for HPV testing has already been adopted by some countries, while others have started trials to evaluate its incorporation into national cervical cancer screening programs. Self-sampling may result in more individuals willing to participate in cervical cancer screening, because it removes many of the barriers that prevent women, especially those in low socioeconomic and minority populations, from participating in regular screening programs. Several studies have shown that the majority of women who have been underscreened but who tested HPV-positive in a self-obtained sample, will visit a clinic for follow-up diagnosis and management. Additionally, a self-collected sample can also be used for vaginal microbiome analysis, which can provide additional information about HPV infection persistence as well as vaginal health in general.

The term ‘Hallmarks of Cancer’ was coined by Hanahan and Weinberg in their influential reviews and they described genome instability as a property of cells enabling cancer development [1, 2]. Accurate DNA replication of genomes is central to diminish genome instability. Here, the understanding of the initiation of DNA synthesis in origins of DNA replication to start leading strand synthesis and the initiation of Okazaki fragment on the lagging strand are crucial to control genome instability. Recent findings have provided new insights into the mechanism of the remodelling of the prime initiation enzyme, DNA polymerase α-primase, during primer synthesis, how the enzyme complex achieves lagging strand synthesis, and how it is linked to replication forks to achieve optimal initiation of Okazaki fragments. Moreover, the central roles of RNA primer synthesis by Pol-prim in multiple genome stability pathways such as replication fork restart and protection of DNA against degradation by exonucleases during double-strand break repair is discussed.

Cells respond to DNA double-strand breaks by initiating DSB repair and ensuing a cell cycle checkpoint. The primary responder to DSB repair is non-homologous end joining, an error prone repair pathway. However, when DSBs are generated after DNA replication in the G2 phase of the cell cycle, a second DSB repair pathway, homologous recombination, can come into action. Both ATM and ATR are important for DSB-induced DSB repair and checkpoint responses. One method of ATM and ATR working together is through the DNA end-resection of DSBs. As a readout and marker of DNA end-resection, RPA is phosphorylated at Ser4/Ser8 of the N-terminus of RPA32 in response to DSBs. Here, the significance of RPA32 Ser4/Ser8 phosphorylation in response to DNA damage, specifically in S phase to G2 phase of the cell cycle is examined. RPA32 Ser4/Ser8 phosphorylation in G2 synchronized cells is necessary for increases in TopBP1 and Rad9 accumulation on chromatin and full activation of the ATR-dependent G2 checkpoint. In addition, our data suggest RPA Ser4/Ser8 phosphorylation modulates ATM-dependent KAP-1 phosphorylation and Rad51 chromatin loading in G2 cells.

DNA damage repair lies at the core of all cells’ survival strategy, including cancerous. Therefore, targeting such repair mechanisms forms the major goal of cancer therapeutics. The mechanism of DNA repair has been tousled with the discovery of multiple kinases. Recent studies on Tousled like Kinases have brought significant clarity on the effectors of these kinases which stands to regulate DSB repair. In addition to their well-established role in the DDR and cell cycle checkpoint mediation after DNA damage or inhibitors of replication, their suspected involvement in the actual DSB repair process has more recently been strengthened by the important finding that TLK1 phosphorylates RAD54 and regulates some of its activities and localization in the cell. Earlier findings of its regulation of RAD9 during checkpoint deactivation as well as defined steps during NHEJ ends processing were earlier hints of its important involvement broadly in DSB repair. All this has opened up new avenues to target cancer cells in combination therapy with genotoxins and TLK inhibitors.

Head and neck squamous cell carcinomas (HNSCCs) develop from the mucosa of the oral cavity, pharynx, and larynx. The methylation levels of Septin 9 (SEPT9) and short stature homeobox 2 (SHOX2) genes in ccfDNA are considered pan-cancer biomarkers and have shown prognostic value in preliminary reports in HNSCC. Liquid biopsy is a non-invasive procedure that collects tumor-derived molecules including circulating cell-free DNA (ccfDNA). Here, we developed a ddPCR-based assay to detect the DNA methylation levels of plasma circulating SEPT9 and SHOX2 in patients with HNSCC. We first set up the assay on commercial methylated and un-methylated DNA. Then, the dynamic changes of the methylation levels of SEPT9 and SHOX2 were quantified in 20 patients during the follow-up. The results highlighted: i) the capability of the ddPCR-based assay in detecting very low copies of methylated molecules; ii) the significant decrease in methylation levels of SEPT9 and SHOX2 in plasma of HNSCC patients at the first time points of follow-up respect to T0; iii) a different trend of longitudinally DNA methylation variations associable to the clinicopathological features of the patients. The absolute quantification of the methylation levels of SEPT9 and SHOX2 in HNSCC may be used for risk stratification and disease monitoring.

Forensic genetic genealogy, a technique leveraging new DNA capabilities and public genetic databases to identify suspects, raises specific considerations in a law enforcement context. Use of this technique requires consideration of its scientific and technical limitations, including the composition of current online datasets, and consideration of its scientific validity. Additionally, forensic genetic genealogy needs to be considered in the relevant legal context to determine the best way in which to make use of its potential to generate investigative leads while minimising its impact on individual privacy. This article presents these issues from an Australian perspective, with the observations and conclusions likely to be applicable to other jurisdictions.

One of creators of quantum mechanics P. Jordan in his work on quantum biology claimed that life's missing laws were the rules of chance and probability of the quantum world. The article presents author’s results of studying frequencies (or probabilities) of nucleotides on so-called epi-chains of long DNA sequences of various eukaryotic and prokaryotic genomes. DNA epi-chains are algorithmically constructed subsequencies of DNA nucleotide sequences. According to the algorithm of construction of any epi-chain of the order n, the epi-chain is such nucleotide subsequence, in which the numerations of adjacent nucleotides differ by natural number n (n = 1, 2, 3, 4,…). Correspondingly each epi-chain of order n ≥ 2 contains n times less nucleotides than the original DNA sequence. The presented results unexpectedly discover that in long single-stranded and double-stranded DNA of any tested genome its DNA epi-chains of different orders n (values n are not too large) have practically identical frequencies (or probabilities) of each kind of nucleotides. These data allow considering DNA as a regular rich set of epi-chains, which can play a certain role in genetic and epigenetic phenomena as the author belives. Appropriate rules of nucleotide frequencies on epi-chains of long DNA sequences are formulated for further their tests on a wider set of genomes. These results testify on existence of long-range coherence in long DNA and remind the Fröhlich's theory of long-range coherence in biological systems. The phenomenological data are discussed from different standpoints: the DNA double helices and helical antennas with circular polarizations of electromagnetic waves; relations with the Fröhlich's theory; numerical analysis of DNA epi-chains under binary representations of nucleotides. Results are useful for developing quantum and algebraic biology.

DNA double-strand breakage is the most lethal damage to chromosomal DNA. It activates a series of cellular DNA damage response pathways, including DNA damage sensing, control of cell cycle arrest and apoptosis, and DNA repair. DNA damage response pathways are regulated by complex signaling machineries. Of the intracellular signaling cascades, diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DG) to generate phosphatidic acid (PA). Because both DG and PA serve as second messengers, DGK activity induces a shift of signaling pathways from DG-mediated to PA-mediated cascades, thereby implicating DGK in the regulation of widely various functions. Reportedly, one member of the DGK family, DGKζ, is intimately involved in the regulation of stress responses through p53 and NF-κB. Stresses such as ischemia and infarction cause DGKζ downregulation. Experimental DGKζ depletion renders cells and mice vulnerable to various stressors such as chemotherapeutic agents and ionizing irradiation. Nevertheless, how DGKζ is involved in DNA repair, a critical event of DNA damage response for survival remains unknown. For this study, we examined how DGKζ depletion affects DNA repair mechanisms. We demonstrated that DGKζ depletion causes attenuation of Akt activation and DNA-PK protein expression upon DNA damage, which might engender downregulated BRCA1 protein synthesis and stability. Results suggest that DGKζ depletion attenuates BRCA1-mediated DNA repair machinery, thereby conferring vulnerability to DNA damage.

We have been encouraging practicing gynecologists to adopt molecular diagnostics tests, PCR, and cancer biomarkers, as an alternative enabled by these platforms to traditional Papanicolaou and colposcopy tests, respectively. An aliquot of liquid-based cytology was used for the molecular test [high-risk HPV types, (HR HPV)], another for the PAP test and still one more for the p16/Ki67 dual stain cytology. A total of 4,499 laboratory samples were evaluated, and we found that 25.1% of low-grade samples and 47.9% of high-grade samples after PAP testing had a negative HR HPV-PCR result. In those cases, reported as Pap-negative, 22.1% got a positive HR HPV-PCR result. Dual staining with the p16/Ki67 biomarkers in samples was positive for HR HPV, and 31.7% were also positive for these markers. Of the PCR results positive for any of these high-risk HPV subtypes, n 68.3% we did not to find evidence for the presence of cancerous cells, highlighting the importance of performing dual staining with p16/Ki67 after PCR, to avoid unnecessary colposcopies. Encountered challenges are a deep-rooted social reluctance in Mexico to abandon traditional Pap smears and the opinion of many specialists, we still believe that colposcopy continues to be a preferred procedure over dual staining protocol.

Lung cancer is the leading cause of cancer death worldwide therefore studies about the etiological factors and carcinogenesis are important.The aim of the study is to detect the presence and types of Human papilloma virus (HPV) in lung cancer and non-tumoral lung and Epidermal Growth Factor Receptor (EGFR) mutation prevalance in lung cancer with Polymerase Chain Reaction (PCR) method.Fifty patients who were histopathologically diagnosed lung cancer and 7 patients with non-neoplastic lung disease were enrolled in the study. HPV positivity was detected in 75.4% of the patients. The rate of high-risk HPV positivity was 100% in adenocarcinomas, 64.5% in squamous cell carcinomas, and 57% in non-neoplastic lung. HPV 51 was the most frequent type followed by HPV 16 (43.9%). There was no statistically significant relationship between HPV infection and age, gender and smoking history and EGFR mutation. The prevalence of HPV positivity is variable in lung cancer in different studies and this may be due to many factors including HPV detection methods, number of patients, geographic regions. New studies about the role of HPV infection need to be performed in order to obtain information about the use of prophylactic and theurepatic agents in lung cancer.

Background: Penile squamous cell carcinoma (PSCC) is classified into two prognostically distinct types: human papillomavirus (HPV)-associated and HPV-independent. Conversely, the impact of p53 status on prognosis remains controversial. We correlated HPV and p53 status with prognosis in a large series of PSCC patients. p53 was analysed according to a recently described immunohistochemical (IHC) pattern-based framework that includes two normal (scattered, mid-epithelial) and four abnormal patterns (diffuse, basal overexpression, cytoplasmic and null) and closely correlates with TP53 mutational status. Methods: A total of 122 patients with surgically treated PSCC in three hospitals in Barcelona, Spain, were included. Based on HPV in situ hybridization and p16 and p53 IHC expression, the tumors were classified into three molecular types: HPV-associated, HPV-independent/p53 normal, and HPV-independent/p53 abnormal. All patients were followed for at least 22 months (median 56.9 months), and disease-specific survival (DSS) was analysed. Results: Thirty-six tumors (29%) were HPV-associated, 35 (29%) were HPV-independent/p53 normal, and 51 (42%) were HPV-independent/p53 abnormal. Disease-related deaths were observed in 3/36 (8%), 0/35 (0%) and 14/51 (27%) of the patients, respectively (p&lt;0.001). A total of 7/14 deaths in the latter group were patients with tumors showing p53 patterns not recognized in the classical p53 IHC interpretation (basal, null, cytoplasmic). According to our multivariate analysis, HPV-independent/p53 abnormal tumors and advanced stage were associated with impaired DSS (hazard ratio=23.4, 95% confidence interval [CI]= 2.7-3095.3; p=0.001 and 16.3, 95% CI=1.8-2151.5; p=0.008, respectively). CONCLUSION: Compared with patients with HPV-associated and HPV-independent/p53-normal PSCC, patients with HPV-independent/p53 abnormal PSCC have worse clinical outcomes. p53 IHC results define two prognostic categories in HPV-independent PSCC: HPV-independent/p53-normal tumors as low-risk tumors, whereas HPV-independent/p53-abnormal tumors as aggressive neoplasms.

Platinum(II) complexes have been found to be effective against cancer cells. Cisplatin curbs cell replication by interacting with the deoxyribonucleic acid (DNA), eventually leading to cell death and reducing cell proliferation. In order to investigate the ability of platinum complexes to affect cancer cells, two examples from the class of polyflurophenylorganoamidoplatinum(II) complexes were synthesised and tested on isolated DNA. The two compounds trans-[N,N’-bis(1,2,3,5,6-pentafluorophenyl)ethane-1,2-diaminato(1-)](2,3,4,5,6-pentafluorobenzoato)(pyridine)platinum(II) (PFB), and trans-[N,N’-bis(1,2,3,5,6-pentafluorophenyl)ethane-1,2-diaminato(1-)](2,4,6-trimethylbenzoato)(pyridine)platinum(II) (TMB) were compared with cisplatin through their reaction with DNA. Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopy was applied to analyse the interaction of the Pt^(II) complexes with DNA in the hydrated, dehydrated and rehydrated state. These were compared with control DNA in acetone/water (PFB, TMB) and isotonic saline (cisplatin) under the same conditions. Principle Component Analysis (PCA) was applied to compare the ATR-FTIR spectra of the untreated control DNA with spectra of PFB and TMB treated DNA samples. Disruptions in the conformation of DNA treated with the Pt^(II) complexes upon rehydration were mainly observed by monitoring the position of the IR-band around 1711 cm^-1 assigned to the DNA base-stacking vibration. Furthermore, other intensity changes in the phosphodiester bands of DNA at ~1234 cm^-1 and 1225 cm^-1 and shifts in the dianionic phosphodiester vibration at 966 cm^-1 were observed. The isolated double stranded DNA (dsDNA) or single stranded DNA (ssDNA) showed different structural changes when incubated with the studied compounds. PCA confirmed PFB had the most dramatic effect by denaturing both dsDNA and ssDNA. Both compounds, along with cisplatin, induced changes in DNA bands at 1711, 1088, 1051 and 966 cm^-1 indicative of DNA conformation changes. The ability to monitor conformational change with infrared spectroscopy paves the way for a sensor to screen for new anticancer therapeutic agents.

Four 1,10-phenanthroline derivatives (1-4) have been synthesized as potential telomeric DNA binders, three substituted in their chains with thiosemicarbazones (TSCs), the neutral compound (1) and two ionic derivatives (PF6¯ and BF4¯ salts, 2 and 3, respectively), and a fourth corresponding to a 4-phenylthiazole derivative (4). Quadruplex and dsDNA interactions have been preliminarily studied, especially for the neutral derivative 1, by FRET-based DNA melting assays, equilibrium dialysis (both competitive and non-competitive), circular dichroism and viscosity titrations. The TSC derivatives bind and stabilize the telomeric Tel22 quadruplex more efficiently than dsDNA, with an estimated 24-fold selectivity determined by equilibrium dialysis for compound 1. In addition, cytotoxic activity against different tumor cells (PC-3, DU145, HeLa, MCF-7 and HT29), and two non-tumor cell lines (HFF-1 and RWPE-1) has been evaluated. Except for the 4-phenylthiazole derivative, which was inactive, the compounds show moderate cytotoxic properties, with the salts displaying lower IC50 values, compared to the neutral TSC. However, the neutral derivative was the only compound that exhibited a modest selectivity in the case of prostate cells (tumor PC-3 versus healthy RWPE-1). Cell cycle analysis and Annexin V/PI assays revealed that the compounds can produce cell death by apoptosis, an effect that has proven similar to that demonstrated by other known 1,10-phenanthroline G4 ligands endowed with antitumor properties, such as PhenDC3 or PhenQE8.

B chromosomes are supernumerary chromosomes which are found in addition to the normal standard chromosomes (A chromosomes). B chromosomes are well known to accumulate several types of repeats. Although the evolution of B chromosomes has been subject of numerous studies, the mechanisms of accumulation and evolution of repetitive sequences is not fully understood. Recently, new genomic approaches have shed light on the origin and accumulation of different classes of repetitive sequences in the process of B chromosome formation and evolution. Here we discuss the impact of repetitive sequences accumulation on the evolution of plant B chromosomes.

Cholangiocarcinoma is an epithelial malignancy arising in the region between the intrahepatic bile ducts and the ampulla of Vater at the distal end of the common bile duct. The effect of current chemotherapy regimens against cholangiocarcinoma is limited, and the prognosis of patients with cholangiocarcinoma is poor. Aberrant DNA methylation and histone modification induce silencing of tumor suppressor genes and chromosomal instability during carcinogenesis. Studies have shown that the tumor suppressor genes and microRNAs (miRNAs) including MLH1, p14, p16, DAPK, miR-370 and miR-376c are frequently methylated in cholangiocarcinoma. Silencing of these tumor suppressor genes and miRNAs plays critical roles in the initiation and progression of cholangiocarcinoma. In addition, recent studies have demonstrated that DNA methylation inhibitors induce expression of endogenous retroviruses and exert the anti-tumor effect of via an anti-viral immune response. Aberrant DNA methylation of tumor suppressor genes and miRNAs could be a powerful biomarker for diagnosis and treatment of cholangiocarcinoma. Epigenetic therapy with DNA methylation inhibitors hold considerable promise for the treatment of cholangiocarcinoma through re-activation of tumor suppressor genes and miRNAs as well as induction of an anti-viral immune response.

Astronauts in space are subject to a continuous bombardment of ionizing radiation. The Earth's magnetic field and the ISS shield some biologically damaging particles traveling through. Still, travel beyond low-Earth orbit and extravehicular activities are exceedingly more dangerous and there is a concern for the acute and late-occurring adverse health effects befalling astronauts. So, it is vital to consider the current tools and models used to describe and study the organic consequences of ionizing radiation exposure. It is equally important to see where these models may improve. This article reviews the historical development and current state of knowledge of radiation effects impacting astronauts in orbit. We explain the space radiation environment, cellular microenvironment, and how these may be incorporated in radiobiological models to aid in our understanding of the influence space travel may have on astronaut health. The topics discussed in this paper include a review of DNA damage and repair mechanisms and the numerical models that aim to explain the biological effects resulting from ionizing radiation damage. Historically, radiobiological models focused on how radiation damages nuclear DNA, built upon the hypotheses of Crowther and Lea in the 1940s and 1960s, and neglected other sub-cellular targets outside of nuclear DNA.

(1) Background: The prediction of cervical lesions evolution is a challenge for clinicians. The prospective study aimed to determine and compare the predictive accuracy of cytology, HPV genotyping, and p16/Ki67 dual staining alone or in combination with personal risk factors for the prediction of progression, regression or persistence of cervical lesions in human papillomavirus (HPV)-infected patients; (2) Methods: This prospective study included HPV-positive patients with or without cervical lesions that underwent follow-up. Descriptive statistics and sensitivity analysis for individual or combined index tests were used for data analysis; (3) Results: The highest predictive performance for the progression of cervical lesions was achieved by a model that comprised a Pap smear suggestive of high-grade squamous intraepithelial lesion (HSIL), the presence of 16/18 HPV strains, a positive p16/Ki67 dual staining result along with the presence of at least 3 clinical risk factors, which had a sensitivity (Se) of 74.42%, a specificity of 97.92%, an area under the receiver operating curve (AUC) of 0.961, and an accuracy of 90.65%. The prediction of cervical lesions regression or persistence was modest; (4) Conclusions: Multiple testing or new biomarkers should be used to improve HPV-positive patient surveillance, especially for cervical lesion regression or persistence prediction.

To better understand anogenital warts (AGW) natural history and dynamic of HPV6/11 infection in regional hairs, 32 newly diagnosed AGW male patients and 32 age-matched healthy controls were closely followed. During enrollment and six follow-up visits (every 2.6 months) 43 AGW tissue and 1,232 anogenital and eyebrow hair samples were collected. This represents the closest longitudinal monitoring of AGW patients to date. Patients were treated according to standard-of-care. HPV6/11 prevalence was 19.9% in patients’ hair samples (HPV6 B1 in 87.5%) and 0% in controls. The highest HPV6/11 prevalence was found in pubic hairs (29.0%) and lowest in eyebrows (7.1%). Odds for HPV6/11-positive hairs increased with smoking, shaving anogenital region and age. A close association between HPV6/11 presence in hairs and clinically visible AGW was observed. The proportion of patients with visible AGW and HPV6/11-positive hairs declined during follow-up with similar trends. No particular HPV6/11 variant was linked with increased AGW recurrence, but sublineage HPV6 B1 showed significantly higher clearance from hairs. Despite treatment, 78.1% and 62.5% of AGW patients experienced one and two/more post-initial AGW episodes, respectively. Patients having HPV6/11-positive hairs or visible AGW at preceding visit demonstrated substantially higher odds for presenting with visible AGW in subsequent visit.

The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is rising in the West, but little is known in Asia. This study elucidated changes in the incidence and HPV-positive portion of OPSCC in Hong Kong. Data from population-based cancer registry were used to analyze the incidence of OPSCC in associate with other head and neck cancers. Archived tumour tissues were tested for HPV. From 1986 to 2020, there was a marked decrease in the incidence of nasopharyngeal and laryngeal cancers, but a persistent increase in OPSCC from 36 cases in 1986 to 116 cases in 2020. The average positive rate for high-risk HPV was 36.1% (112/310) among OPSCC diagnosed in 2010-2020. The HPV positive rate in recent years was significantly higher than earlier cases (tonsil SCC: 64.7% (55/85) in 2016-2020 vs. 40.4% (19/47) in 2010-2015, P = 0.007). Patients with HPV-positive tonsil cancers were significantly younger than those negative (mean [SD]: 58.9 [9.9] vs. 64.3 [13.3] years, P = 0.006), but no significant difference between genders. A persistent increase in the incidence of oropharyngeal cancer over the last few decades was observed in Hong Kong, which can be explained by the remarkable increase in HPV-positive tonsil cancers.

Cervical cancer is the fourth most common malignancy in women worldwide, although it is preventable with prophylactic HPV vaccination. HPV transmission-dynamic models can predict the potential for global elimination of cervical cancer. The random network model is a new approach that allows individuals to be followed, and to implement a given vaccination policy according to their clinical records. We developed an HPV transmission dynamics model on a lifetime sexual partners network based on individual contacts, also accounting for the sexual behavior of men who have sex with men (MSM). We analyzed the decline in the prevalence of HPV infection in a scenario of 75% and 90% coverage for both sexes. An important herd immunity effect for men and women was observed in the heterosexual network, even with 75% coverage. However, HPV in-fections are persistent in the MSM population, with sustained circulation of the virus among un-vaccinated individuals. Coverage around 75% of both sexes would be necessary to eradicate HPV-related conditions in women within five decades. Nevertheless, the variation in the decline in infection in the long term between vaccination coverage of 75% and 90% is relatively small, suggesting that reaching coverage of around 70-75% in the heterosexual network may be enough to confer high protection. Nevertheless, HPV eradication maybe achieved if men’s coverage is strictly controlled. This accurate representation of HPV transmission demonstrates the need to maintain high HPV vaccination coverage, especially in men, for whom the cost-effectiveness of vaccination is questioned.

Environmental DNA (eDNA) sampling has emerged as a powerful approach for monitoring biodiversity in the context of diverse terrestrial and aquatic ecosystems, and has broad potential for both environmental surveys and species management. eDNA studies focusing on plant and animal species have capitalized on analytical methodologies developed originally for metagenomic studies of microorganisms, and on technological improvements in sample collection. However, while eDNA studies have proliferated rapidly, efforts to standardize sampling and analytical methods are still nascent. Critically, fundamental data concerning the distribution and persistence of eDNA in different ecological contexts are lacking, complicating both confidence in species detection and comparability between studies. We propose that key deficits could be addressed by using well-designed synthetic DNA standards or tracers, which are widely used in fields ranging from medical diagnostics to hydrology. In-field application of a standardized mixture of barcoded synthetic DNA fragments of varying lengths and concentrations that are recovered concommitantly with eDNA sampling should provide critical yet missing data on environmental DNA distribution and turnover, as well as an internal molecular standard to enhance both species detection and comparability between eDNA studies.

Methylation of cytosines at CpG sites in DNA, carried out by de novo by DNA methyltransferase Dnmt3a, is a basic epigenetic modification involved in gene regulation and genome stability. Aberrant CpG methylation in gene promoters leads to oncogenesis. In oncogene promoters, CpG sites often colocalize with guanine-rich sequences capable of folding into G-quadruplexes (G4s). Our in vitro study aimed to investigate how parallel G4s formed by a sequence derived from the c-MYC oncogene promoter region affect the activity of the Dnmt3a catalytic domain (Dnmt3a-CD). For this purpose, we designed synthetic oligonucleotide constructs: c-MYC G4-forming oligonucleotide and linear double-stranded DNA containing an embedded stable extrahelical c-MYC G4. The topology and thermal stability of G4 structures in these DNA models were analyzed by physicochemical techniques. We showed that Dnmt3a-CD specifically binds to an oligonucleotide containing c-MYC G4, resulting in inhibition of its methylation activity. c-MYC G4 formation in a double-stranded context significantly reduce Dnmt3a-CD-induced methylation of a CpG site located in close proximity to the quadruplex structure; this effect depends on the distance between the non-canonical structure and the specific CpG site. One would expect DNA hypomethylation near the G4 structure, while regions distant from this non-canonical form would maintain a regular pattern of high methylation levels. We hypothesize that the G4 structure sequesters the Dnmt3a-CD and impedes its proper binding to B-DNA, resulting in hypomethylation and activation of c-MYC transcription.

A large body of evidence indicates that environmental agents can induce alterations in DNA methylation (DNAm) profiles. Radiofrequency electromagnetic fields (RF-EMFs) are radiations emitted by everyday devices which have been classified as “possibly carcinogenic”, however their biological effects are unclear. As aberrant DNAm of genomic repetitive elements (RE) may promote genomic instability, here we sought to determine whether exposure to RF-EMFs could affect DNAm of different classes of RE, such as long interspersed nuclear element1s (LINE-1), Alu short interspersed nuclear element and ribosomal repeats. To this purpose, we analysed DNAm profiles of cervical cancer and neuroblastoma cell lines (HeLa, BE(2)C and SH-SY5Y) exposed to 900 MHz GSM-modulated RF-EMF through an Illumina-based targeted deep bisulfite sequencing approach. Our findings showed that radiofrequency exposure did not affect DNAm of Alu elements in any of the cell lines analysed. Conversely, it influenced DNAm of LINE1 and ribosomal repeats in terms of both average profiles and organization of methylated and un-methylated CpG sites, in different ways in each of the three cell lines studied.

Here, our data provide the first evidence for the existence of a previously unknown receptive system formed by novel DNA- and RNA-based receptors in eukaryotes. This system, named the TR-system, is capable of recognizing and generating a response to different environmental factors and has been shown to orchestrate major vital functions of fungi, mammalian cells, and plants.Recently, we discovered the existence of a similar regulatory system in prokaryotes. These DNA- and RNA-based receptors are localized outside of the membrane forming a type of a network around cells that respond to a variety of chemical, biological, and physical factors and enabled the TR-system to regulate major aspects of eukaryotic cell life as follows: growth, including reproduction and development of multicellular structures; sensitivity to temperature, geomagnetic field, UV, light, and hormones; interaction with viruses; gene expression, recognition and utilization of nutrients. The TR-system was also implicated in cell memory formation and was determined to be responsible for its maintenance and the forgetting of preceding events. This system is the most distant receptive and regulatory system of the cell that regulates interactions with the outer environment and governs the functions of other receptor-mediated signaling pathways.

Here we present 1. a model for amplicon sequencing 2. a definition of the best assignment of a read to a set of reference sequences 3. strategies and structures for indexing reference sequences and computing the best assign- ments of a set of reads efficiently, based on (ultra)metric spaces and their geometry The models, techniques, and ideas are particularly relevant to scenarios akin to 16S taxonomic profiling, where both the number of reference sequences and the read diversity is considerable.

Structural DNA nanotechnology provides an excellent foundation for diverse nanoscale shapes that can be used in various bioapplications and materials research. From all existing DNA assembly techniques, DNA origami has proven to be the most robust one for creating custom nanoshapes. Since its invention in 2006, building from the bottom up using DNA has drastically advanced, and therefore, more and more complex DNA-based systems have become accessible. So far, vast majority of the demonstrated DNA origami frameworks are static by nature, but interestingly, there also exist dynamic DNA origami devices that are increasingly coming into view. In this review, we discuss DNA origami nanostructures that perform controlled translational or rotational movement triggered by predefined DNA strands, various molecular interactions and/or other external stimuli such as light, pH, temperature and electromagnetic fields. The rapid evolution of such dynamic DNA origami tools will undoubtedly have a significant impact on molecular scale precision measurements, targeted drug delivery and diagnostics, but they can also play a role in development of optical/plasmonic sensors, nanophotonic devices and nanorobotics for numerous different tasks.

We present a numerical study in which large-scale bulk simulations of self-assembled DNA constructs have been carried out with a realistic coarse-grained model. The investigation aims at obtaining a precise, albeit numerically demanding, estimate of the free energy for such systems. We then, in turn, use these accurate results to validate a recently proposed theoretical approach that builds on a liquid-state theory, the Wertheim theory, to compute the phase diagram of all-DNA fluids. This hybrid theoretical/numerical approach, based on the lowest order virial expansion and a nearest-neighbor DNA model, can provide, in an undemanding way, a thermodynamic description of DNA associating fluids that is in semi-quantitative agreement with experiments. We show that the predictions of such scheme are as accurate as the ones obtained with more sophisticated methods. We also demonstrate the flexibility of the approach by incorporating non-trivial additional contributions that go beyond the nearest-neighbor model to compute the DNA hybridization free energy.

Many fundamental molecular techniques (PCR, Microarray, Southern and northern hybridization, siRNA, CRISPR/Cas9 etc.) developed so far shows errors. I wish to highlight these molecular techniques are developed on basis of Watson-Crick DNA model, ignoring the concept of parallel stranded DNA. Through this opinion article, I wish to highlight specificity and accuracy of these molecular techniques can be enhanced by considering both parallel and anti parallel hybridization of DNA. Hopefully my views will also solve issue of irreproducibility in life science research.

Abstract Background In tumors, somatic mutagenesis presumably drives DNA damage response (DDR) via altered regulatory pathways increasing genomic instability and proliferative activity. These considerations led to the standard therapeutic strategy against cancer: the disruption of mutation activated DNA repair pathways of tumors. Purpose Justifying that cancer cells are not enemies to be killed, but rather they are ill human cells having the remnants of physiologic regulatory pathways. Results 1. Genomic instability and cancer development may be originated from the flaw of estrogen signal rather than excessive estrogen signaling. 2. Healthy cells with genomic instability exhibit somatic mutations helping DNA restitution. 3. Somatic mutations in tumor cells aim the restoration of DNA damage rather than further genomic derangement. 4. In tumors, estrogen signal drives the pathways of DNA stabilization leading to apoptotic death. 5. In the peritumoral cellular infiltration, the genomic damage of tumor induces inflammatory cytokine secretion and increased estrogen synthesis. In the inflammatory cells, increased growth factor receptor (GFR) signal confers unliganded activation of estrogen receptors (ERs). 6. In tumor cells responsive to genotoxic therapy, constitutive mutations help the upregulation of estrogen signal and consequential apoptosis. In tumors non responsive to genotoxic therapy, the possibilities for ER activation via either liganded or unliganded pathway, are exhausted leading to farther genomic instability and unrestrained proliferation. Conclusion Understanding the real character and behavior of human tumors at molecular level suggests that we should learn the genome repairing methods of tumors and follow them by supportive therapy rather than provoking additional genomic damages.

The National Institute of Justice reported that current methods for processing sexual assault samples have a high failure rate, with 60 to 80 percent of tested kits unable to produce usable DNA profiles. Even when samples test positive for male DNA, 34 percent of sexual assault kits (SAK) do not yield recovered male DNA after differential extraction. Less than 30% recovery of available sperm DNA contributes to this low success rate. The SpermX™ method (SX) has been shown to recover 80 percent or more of sperm DNA from sexual assault samples. An interlaboratory evaluation compared SX to standard differential extraction (DE) protocols. Mock samples with known ratios of female epithelial cells and sperm cells were processed using both methods. Results revealed that SX consistently provided CODIS up-loadable DNA profiles, even with as few as 25 sperm cells, whereas DE failed to produce usable results. On average, SX yielded a seven-fold increase in the recovery of unshared male alleles compared to DE. In conclusion, SX outperformed DE in recovering higher quantities of male DNA with minimal female carryover in sexual assault-type samples. This improved success rate in obtaining usable DNA profiles can significantly aid in solving sexual assault cases. Keywords: Differential extraction, Sexual Assault Kit (SAK), Sperm DNA, STRmix™, Combined DNA Index System (CODIS), Forensic DNA analysis, Low Sperm Samples, DNA Mixtures, Autosomal STR Analysis, SpermX.

Comprehensive studies into the various causes of this ubiquitous disease have been prompted by the worldwide increase in cancer incidence. There are many potential causes of cancer, but environmental factors are of particular concern now. This abstract explores the complex link between environmental factors and the growing cancer epidemic, shedding light on the role that our immediate environment plays in the emergence of cancers. The environment can contain carcinogenic agents that gradually influence the course of cancer, including air pollutants, water contaminants, workplace exposures, and industrial activities. The ways through which environmental carcinogens may cause DNA damage and unchecked cell proliferation are discussed in this abstract. Environmental justice and the moral necessity to reduce inequities in exposure and health effects are highlighted to underline the disproportionate impact on vulnerable groups. The study presented here highlights the need for preemptive action to reduce environmental risks. Society can reduce the hidden threat posed by environmental carcinogens through strict legislation, sustainable practices, and community-driven initiatives. In order to lessen the cancer burden and secure a healthier future for all, the authors of this abstract argue that there must be a concerted effort to create surroundings that promote health and well-being.

Topoisomerases, common targets for anti-tumor therapeutics, are crucial enzymes for DNA replication, transcription, and many other aspects of DNA metabolism. The potential anti-cancer effect of thiosemicarbazones (TSC) and metal-TSC complexes has been demonstrated by targeting several biological processes, including DNA metabolism. Human topoisomerases were discovered among the molecular targets for TSCs, and metal-chelated TSCs specifically displayed significant inhibition. The processes by which metal-TSCs or TSCs inhibit topoisomerases are still being studied. In this brief review, we summarize the TSCs and metal-TSCs that inhibit various types of human topoisomerases.

Phenotypes are necessary for genomic evaluations and management. Sometimes genomics can be used to measure phenotypes when other methods are difficult or expensive. Prolificacy of bulls used in multiple-bull pastures for commercial beef production is an example. A retrospective study of 79 bulls aged 2-year-old and older used 141 times in 4-5 pastures across 4 years was used to estimate repeatability from variance components. Traits available before each season’s use were tested for predictive ability. Sires were matched to calves using individual genotypes and evaluating exclusions. A lower cost method of measuring prolificacy was simulated for 5 pastures using the bulls’ genotypes and pooled genotypes to estimate average allele frequencies of calves and of cows. Repeatability of prolificacy was 0.62 ± 0.09. A combination of age-class and scrotal circumference accounted for less than 5 % of variation. Simulated estimation of prolificacy by pooling DNA of calves was accurate. Adding pooling of cow DNA or actual genotypes both increased accuracy about the same. Knowing a bull’s prior prolificacy would help predict future prolificacy for management purposes and could be used in genomic evaluations and research with coordination of breeders and commercial beef producers.

The ability to predict physical characteristics from DNA presents significant opportunities for forensic science. Giving scientists an ability to make predictions about the donor of genetic material at a crime scene can then give investigators new intelligence leads for cold cases where DNA evidence has not identified any person of interest. However, the interpretation of this new form of intelligence requires careful analysis. The responses to an online survey, conducted in 2018-19, were used to examine how actors in the criminal justice system assess and interpret different types of DNA evidence and intelligence. The groups of focus for the survey were investigators, legal practitioners and the general public (as potential jurors). Several statistically significant effects were identified based on occupation and whether an individual had prior exposure to new DNA technology. Monitoring how those involved in interpreting reports from different types of DNA evidence and intelligence interpret them helps to ensure that decisions are made based on a sound understanding of their capabilities and limitations and may inform broader training and awareness strategies.

A fully analytical treatment of the base-pair and codon dynamics in double-stranded DNA molecules is introduced, by means of a realistic treatment which considers different mass values for G, A, T, and C nucleotides and takes into account the intrinsic three-dimensional, helicoidal geometry of DNA in terms of a Hamitonian in cylindrical coordinates. Within the framework of the Peyrard-Dauxois-Bishop model we consider the coupling between stretching and stacking radial oscillations as well as the twisting motion of each base pair around the helix axis. By comparing the linearized dynamical equations for the angular and radial variables when going from the bp local scale to the longer triplet codon scale, we report an underlying hierarchical symmetry. The existence of synchronized collective oscillations of the base-pairs and their related codon triplet units are disclosed from the study of their coupled dynamical equations. The possible biological role of these correlated, long-range oscillation effects in double standed DNA molecules containing mirror-symmetric codons of the form XXX, XX’X, X’XX’, YXY, and XYX is discussed in terms of the dynamical equations solutions and their related dispersion relations.

There is a major clinical need for accurate biomarkers for prostate cancer prognosis, to better inform treatment strategies and disease monitoring. Current clinically recognised prognostic factors, including prostate-specific antigen (PSA) levels, lack sensitivity and specificity in distinguishing aggressive from indolent disease, particularly in patients with localised intermediate grade prostate cancer. There has therefore been a major focus on identifying molecular biomarkers that can add prognostic value to existing markers, including investigation of DNA methylation, which has a known role in tumorigenesis. In this review, we will provide a comprehensive overview of the current state of DNA methylation biomarker studies in prostate cancer prognosis, and highlight the advances that have been made in this field. We cover the numerous studies into well-established candidate genes, and explore the technological transition that has enabled hypothesis-free genome-wide studies and the subsequent discovery of novel prognostic genes.

Background: The presence of HIV residual replication markers was investigated among distinct subgroups of individuals on antiretroviral treatment (ART). Methods: One hundred sixteen patients were distributed into 5 treatment groups: first-line suppressive ART with a non-nucleoside analog reverse-transcriptase inhibitor (NNRTI) (n = 26), first-line suppressive ART with boosted protease inhibitors (PI-r) (n = 25), suppressive salvage therapy using PI-r (n = 27), suppressive salvage therapy with PI-r and raltegravir (n = 22) and virologic failure (n = 16). Episomal and total DNA quantitation was evaluated. HIV antibody and LPS quantitation was performed. Results: Episomal DNA was positive in 26% to 38% of individuals under suppressive ART, and it was higher among ART virologic failure group (p = 0.04). HIV proviral load was higher among patients with detectable episomal DNA (p = 0.01). Individuals receiving initial PI-r treatment presented lower HIV antibody (p = 0.027) and LPS (p = 0.029) levels than individuals receiving NNRTI. There was a negative correlation between episomal DNA quantitation and the duration of suppressive ART (p = 0.04), CD4+ T-cell count (p = 0.08), and CD8+ T-cell count (p = 0.07). Conclusions: Residual HIV replication has been inferred among individuals under suppressive ART according to episomal DNA detection. Residual replication may decrease with longer periods of suppressive ART and higher levels of CD4+ and CD8+ T cells. The relationship between episomal DNA and total DNA suggests there is a replenishment of the proviral reservoir. Lower antibody and LPS levels among patients with initial PI-r ART suggest these regimens may more effectively suppress HIV, more effectively decreasing HIV antigenic component.

High concentrations of Na⁺ or [Co(NH₃)₆]³⁺ can induce the B to Z conformational transition in alternating (dC-dG) oligo and polynucleotides. The use of short DNA oligomers (dC-dG)₄ and (dm⁵C-dG)₄ as models can allow a thermodynamic characterization of the transition. Both form right handed double helical structures (B-DNA) in standard phosphate buffer with 115 mM Na⁺ at 25 ^oC. However, at 2.0 M Na⁺ or 200 mM [Co(NH₃)₆]³⁺, (dm⁵C-dG)₄ assumes a left handed double helical structure (Z-DNA) while the unmethylated (dC-dG)₄ analogue remains right handed under those conditions. We have previously demonstrated that the enthalpy of the transition at 25 ^oC for either inducer can be determined using isothermal titration calorimetry (ITC) [Ferreira, J. M. & Sheardy, R. D., Biophys. J. 2006, 91, 1–7]. Here, ITC is used to investigate the linkages between temperature, water activity and DNA conformation. We found that the determined enthalpy for each titration varied linearly with temperature allowing determination of the heat capacity change (DC_p) between the initial and final states. As expected, the DC_p values were dependent upon the cation (i.e. Na⁺ vs [Co(NH₃)₆]³⁺) as well as the sequence of the DNA oligomer (i. e., methylated vs unmethylated). Osmotic stress experiments were carried out to determine the gain or loss of water by the oligomer induced by the titration. The results are discussed in terms of solvent accessible surface areas, electrostatic interactions and the role of water.

Oxidative and nitrosative stress are a common problem when manipulating gametes in vitro. In vitro development in mammalian embryos is highly affected by culture conditions, especially by reactive oxygen species (ROS) and reactive nitrogen species (RNS), because its absence or over production causes embryo arrest and changes in gene expression. Melatonin in gamete co-incubation during IVF has deleterious or positive effects depending on the concentration used in culture medium, demonstrating the delicate balance that must exist between antioxidant and pro-oxidant activity. Further research is needed to better understand the possible impact of melatonin on the different IVP steps in domestic animals, especially in seasonal breeds where this neuro-hormone system highly regulates its reproduction physiology.

In E. coli DNA replication forks stall on average once per cell cycle. When this occurs, replisome components disengage from the DNA, exposing an intact, or nearly intact fork. Consequently, the fork structure must be regressed away from the initial impediment so repair can occur. Regression is catalyzed by the powerful, monomeric DNA helicase, RecG. During this reaction, the enzyme couples unwinding of fork arms to rewinding of duplex DNA resulting in the formation of a Holliday junction. RecG works against large opposing forces enabling it to clear the fork of bound proteins. Following subsequent processing of the extruded junction, the PriA helicase mediates reloading of the replicative helicase DnaB leading to the resumption of DNA replication. The single-strand binding protein (SSB) plays a key role in mediating PriA and RecG functions at forks. It binds to each enzyme via linker/OB-fold interactions and controls fork loading sites in a substrate-dependent manner that involves helicase remodeling. Finally, it is displaced by RecG during fork regression. The intimate and dynamic SSB-helicase interactions play key roles in ensuring fork regression and DNA replication restart.

This review focuses on the regulation and modulation of human DNA polymerase δ (Pol δ). The emphasis is on mechanisms that regulate the activity and properties of Pol δ in DNA repair and replication. The areas covered are the degradation of the p12 subunit of Pol δ, which converts it from a heterotetramer (Pol δ4) to a heterotrimer (Pol δ3), in response to DNA damage and also during the cell cycle. The biochemical mechanisms that lead to degradation of p12 are reviewed, as well as the properties of Pol δ4 and Pol δ3 that provide insights into their functions in DNA replication and repair. The second focus of the review involves the functions of two Pol δ binding proteins, PDIP46 and PDIP38, both of which are multi-functional proteins. PDIP46 is a novel activator of Pol δ4, and the impact of this function is discussed in relation to its potential roles in DNA replication. Several new models for the roles of Pol δ3 and Pol δ4 in leading and lagging strand DNA synthesis that integrate a role for PDIP46 are presented. PDIP38 has multiple cellular localizations including the mitochondria, the splicesosomes and the nucleus. It has been implicated in a number of cellular functions, including the regulation of specialized DNA polymerases, mitosis, the DNA damage response, Mdm2 alternative splicing and the regulation of the Nox4 NADPH oxidase.

Objectives: To evaluate the relationship between the type of conization, the volume and dimensions of the cone, with the persistence/recurrence of CIN 2-3, presence of affected margins and post-cone HR-HPV positivity. Methods: 227 women treated with LLETZ and histologically confirmed CIN2-3 were evaluated between 1996 and 2006 and followed up until June 2016. Age, type of resection according to IFCPC 2011, volume, cone dimensions, margins were studied. of resection, post-cone high-risk human papillomavirus (HR-HPV) status and viral load. Determinants of HR-HPV positivity were estimated using unconditional logistic regression and time to recurrence was assessed using Kaplan-Meier curves. Results: Persistent/recurrent CIN2-3 was found in 12 cases (5.2%), type 1 conization was performed in 81 patients, with 5 recurrences (6.1%), type 2 in 101 patients, with 6 recurrences (5 .9%) and type 3 resection in 45 women, with 1 recurrence (2.2%). Volume and dimensions were not associated with recurrence. The Log-Rank Test did not show a significant difference between the 3 treatments (p= 0.18). The free margins in type 1 were 37%, in type 2 resection 61% and in type 3 71% (p=0.001). Resection type 1 had 15% HR-HPV post positive cone, type 2 reached 16% and type 3 had 9%, this difference being non-significant (p=0.58). The incidence of recurrence at 36 months in type 1 resection was 0.08%, in type 2 treatment it was 0.04% and in type 3 resection it was 0.0%. Conclusions : Type 3 resection had a higher proportion of free margins and lower post-cone HR-HPV positivity, with a lower incidence of persistence/recurrence.

Introduction. Self-sampling has the potential to increase cervical cancer screening (CCS) among women living with HIV (WLWH) in low and middle-income countries (LMICs). However, our understanding of how HPV self-collection studies have been conducted in WLWH is limited. The purpose of this scoping review was to examine the extent to which the HPV self-sampling has been applied among WLWH in LMICs. Method: We conducted multiple searches in several databases for articles published between 2000 and January 2022. With the combination of keywords relating to HPV self-sampling, LMICs, and WLWH, we retrieved over 9,000 articles. We used pre-defined inclusion and exclusion criteria to select relevant studies for this review. Once a study met the inclusion criteria, we created a table to extract each study’s characteristics and classified them under common themes. We used a qualitative descriptive approach to summarize the scoping results. Results: A total of 12 articles were included in the final review. Overall, 3,178 women were enrolled in those studies and 2,105 (66%) of them were WLWH. The self-sampling participation rate was 92.6%. The findings of our study show that 43% of the WLWH in 8 of the studies reviewed tested positive for high-risk HPV (hr-HPV) genotypes, indicating 4 out of 10 WLWH in the studies are at risk of cervical cancer. The prevalence of the hr-HPV in WLWH was 18% higher than that of HIV-negative women. Most women in the study found the self-sampling experience acceptable, easy to use, convenient, and comfortable. Self-sampling performance in detecting hr HPV genotypes is comparable to clinician-performed sampling. However, limited access (i.e., affordability, availability, transportation), limited knowledge about self-screening, doubts about the credibility of self-sampling results, and stigma remain barriers to wide acceptance and implementation of self-sampling. In conclusion, the findings of this review highlight that (a) cervical cancer is a threat to every sexually active woman but for WLWH the threat increases, (b) self-sampling laboratory performance is similar to clinician performed sampling, (c) self-sampling is associated with an increase in cervical cancer screening uptake and (d) WLWH reported a positive experience with self-sampling. However, personal, environmental, and structural barriers challenge the application of self-sampling in LMICs, and these need to be addressed. Keywords: keyword 1; keyword 2; keyword 3 (List three to ten pertinent keywords specific to the article yet reasonably common within the subject discipline.)

Cervical cancer is the fourth common cancer amongst women worldwide. Environmental factors such as smoking and obesity, and recurrent infection by high-risk human papillomavirus subtypes are known to promote progression towards invasive cervical disease. Infection by high-risk HPV is necessary in most cases but not sufficient to develop invasive cervical cancer. Despite a predicted genetic heritability of between 27-36%, known genetic susceptibility loci that may be tumorigenic or influence host response to infection, only account for a small fraction of heritable risk factors so far. Various biobank-driven population based studies and meta-analyses have found corroborative evidence for several risk variants at the 6p21.3 locus (HLA), while many reports of variants outside the HLA region remain to be validated in other cohorts. Here, we review cervical cancer susceptibility variants arising from recent genome-wide association studies and meta-analysis in large cohorts and propose 2q14 (PAX8), 17q12 (GSDMB), and 5p15.33 (CLPTM1L) as consistently replicated non-HLA cervical cancer susceptibility loci. We further discuss the available evidence for these loci, knowledge gaps, future perspectives, and the potential impact of these findings on precision medicine strategies to combat cervical cancer.

The study titled "Molecular Choreography of DNA: Insights and Innovations" explores the intricate dance of DNA, shedding light on its structure, function, and regulation. This comprehensive review delves into the historical significance of DNA research, from Watson and Crick's double helix discovery to recent innovations in genomics and molecular biology. The review highlights DNA's roles in replication, repair, gene regulation, and chromatin dynamics, emphasizing the precision and complexity of its molecular choreography. Innovations like CRISPR-Cas9 gene editing and advanced sequencing technologies have revolutionized our understanding of DNA, opening new avenues for scientific exploration. This study aims to provide readers with a deeper appreciation of DNA's central role in life's choreographed processes.

In our work, using the analysis of DNA barcodes and morphology (wing color, male genitalia, sphragis shape in females), we show that the group of species close to P. mnemosyne is represented by two phylogenetic lineages, the western and eastern ones. The eastern lineage includes P. stubbendorfii, P. glacialis and P. hoenei. The western lineage includes three morphologically similar species, P. mnemosyne (Western Eurasia), P. turatii (southwestern Europe) and P. nubilosus stat. nov. (Turkmenistan and NE Iran), as well as P. ariadne (Altai). The latter species differs from the rest of the group in the presence of red spots on the wings. Parnassius mnemosyne s.s. is represented by four differentiated mitochondrial clusters that show clear association with specific geographic regions. We propose to interpret them as subspecies: P. mnemosyne mnemosyne (Central and Eastern Europe, N Caucasus, N Turkey), P. mnemosyne adolphi (the Middle East), P. mnemosyne orientalis (Tian Shan) and P. mnemosyne gigantea (Gissar-Alai in Central Asia). We demonstrate that in P. ariadne the red spots on the wing evolved as a reversion to the ancestral wing pattern. This reversion is observed in Altai, where the distribution areas of the western lineage, represented by P. ariadne, and the eastern lineage, represented by P. stubbendorfii, overlap. These two species hybridize in Altai, and we hypothesize that the color change in P. ariadne is the result of reinforcement of prezygotic isolation in the contact zone. Lectotype of Parnassius mnemosyne var. nubilosus Christoph, 1873 is designated.

Relative contribution of different repair pathways to the radiation-induced DNA damage responses remains a challenging issue of studying the radiation injury endpoints. Comparative manifestation of homologous recombination (HR) after application of different radiation doses greatly determines an overall effectiveness of recovery in dividing cell after irradiation, since HR is an error-free mechanism intended for repair of DNA double strand breaks (DSB) during S/G2 phases of cell cycle. In this article, we present an experimentally observed evidence of dose-dependent shift in relative contribution of HR in human fibroblasts after X-ray exposure at doses 20-1000 mGy, which is also supported by quantitative modeling of DNA DSB repair. Our findings indicate that the radiation dose increase leads to dose-dependent decrease in relative contribution of HR into the entire repair process.

Although the APOBEC3 family of single-stranded DNA cytosine deaminases are well-known as antiviral factors, these enzymes are rapidly gaining attention as prominent sources of mutation in cancer. APOBEC3 signature single base substitutions, C-to-T and C-to-G in TCA and TCT motifs, are evident in over 70% of human malignancies and dominate the mutational landscape of numerous individual tumors. Recent murine studies have established cause-and-effect relationships, with both human APOBEC3A and APOBEC3B proving capable of promoting tumor formation in vivo. Here, we investigate the molecular mechanism of APOBEC3A-driven tumor development using the murine Fah liver complementation and regeneration system. First, we show that APOBEC3A alone is capable of driving tumor development (without Tp53 knockdown as in prior studies). Second, we show that the catalytic glutamic acid residue of APOBEC3A (E72) is required for tumor formation. Third, we show that an APOBEC3A separation-of-function mutant with compromised DNA deamination activity and wildtype RNA editing activity is defective in promoting tumor formation. Collectively, these results indicate that APOBEC3A is a “master driver” that fuels tumor formation through a DNA deamination-dependent mechanism.

Background: The most important causative agents of neoplasms in the anogenital area is the human papillomavirus (HPV). Due to the anatomical proximity of the genital and anus area and the ease with which HPV infection is transmitted, it seems that patients after treatment of HPV-related gynecological diseases may have increased risk of developing a second HPV-related neoplasm- anal cancer. The aim of the study was to determine the risk of anal intraepithelial neoplasia (AIN) and anal cancer (AC) among patients after treatment of HPV-related gynecological diseases. Methods: We conducted a comprehensive review of available literature in multiple databases. The study was performed following Cochrane Reviewers' Handbook and Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 guidelines. Moreover, we assessed the quality of each study using QUADAS-2. Results: Twenty five studies were included in the final analysis. Patients after treatment of HPV-related gynecological diseases have a significantly higher risk of AC (mean standardized incidence ratio [SIR]= 5.387, mean incidence risk [IR]= 0.096%, mean IR per 100,000 person-years= 10.37), and AIN (mean IR= 23.683%) compared to the population risk. Conclusions: Patients with HPV-related gynecological diseases should constitute a group for which an appropriate primary and secondary screening for AC should be introduced.

The sperm heads of frozen/thawed horse spermatozoa were injected into ovulated mouse oocytes where they decondensed and formed paternal pronuclei in which the DNA damage has been evaluated. The motile spermatozoa exhibit none or minor level of DNA damage and the xenogenic zygotes cleave to the two-cell embryonic stage with regular nuclei and no micronuclei (MNs). On the other hand, the immotile spermatozoa exhibit typically high levels of DNA damage and blastomeres in two-cell stage embryos contain multiple MNs. Moreover, extremely high sperm DNA damage prevents even the cleavage to the two-cell stage.Keywords: keyword 1; keyword 2; keyword 3 (List three to ten pertinent keywords specific to the article yet reasonably common within the subject discipline.)

Dried blood spot (DBS) testing on confetti is one of the most common methods used to collect and extract DNA from field samples for molecular epidemiology of malaria studies. Here, we investigated whether ethanol or other solutions used to clean scissors are a source of sample contamination. DBS were prepared from 3 drops of blood from two Plasmodium falciparum cultures spotted on confetti, and 3 solutions (water, ethanol and DNase) were used to clean scissors between spots during DNA extraction. For each cleaning solution, two blank confetti were used as negative controls. Samples were analyzed by PCR-based genotyping of merozoite surface proteins 1 & 2 (msp-1 and msp-2), and P. falciparum chloroquine resistance transporter (Pfcrt). A total of 15 samples were analyzed. Based on msp-1 and msp-2 amplification, P. falciparum was detected on blank confetti when scissors were washed with ethanol. Based on Pfcrt amplification, DNA of P. falciparum was detected on blank confetti when scissors were cleaned with ethanol or water. No P. falciparum genes were detected on blank confetti when scissors were cleaned with DNase. Scissors cleaned with DNase prevented cross-contamination between samples during processing of dried blood spots, whereas ethanol (which is commonly used) fails to avert cross-contamination.

Two novel sizable multicharged cationic complexes, of the formulae [(η6-[12]CPP)[Ru(η5-Cp)]12]Χ12 and [(η6-[11]CPP)[Ru(η5-Cp)]11]Χ11, CPP= cycloparaphenylene, Cp = cyclopentadienyl, X = [PF6]-, (1), (3) and [Cl]-, (2), (4), were synthesized and characterized using NMR techniques, high-resolution mass spectrometry, and elemental analyses. The complexes, (1) and (3) were stable in acetone and acetonitrile solutions over 48 h. In contrast, the water-soluble, (2) and (4), begins to decompose in aqueous media after 1h, due to the [Cl]- tendency for nucleophilic attack on ruthenium of the {Ru(η5-Cp)} units. Fluorescence quenching experiments conducted during the stability window of (2) with the d(5′-CGCGAATTCGCG-3′)2-EtBr adducts, revealed remarkably high values for Ksv = 1.185 × 104 ± 0.025 M-1 and Kb = 3.162 × 105 ± 0.001 M-1. Furthermore, the cytotoxic activity of (2) against A2780, A2780res, and MCF-7 cancer cell lines shows that it is highly cytotoxic with IC50 values in the range of 4.76 ± 1.85 to 16 ± 0.81 μΜ.

Apurinic/apyrimidinic endonuclease 1 (APE1), also known as redox factor-1 (Ref-1), is a multifunctional protein which is widely existing in living organisms. It can specifically recognize and cleave the DNA in apurinic/apyrimidinic (AP) site in the base excision repair (BER) pathway, as well as regulate the expression of genes to activate some transcription factors. The abnormal ex-pression and disruptions in the biological functions of APE1 are linked to a number of diseases, including inflammation, immunodeficiency, and cancer. Hence, it is extremely desired to monitor the activity of APE1, acquiring a thorough understanding of the healing process of damaged DNA and making clinical diagnoses. Thanks to the advent of DNA nanotechnology, some nanodevices are used to image the activity of APE1 with great sensitivity and simplicity. In this review, we will summarize DNA nanotechnology-empowered fluorescence imaging in the past years for APE1 activity according to the types of DNA probe, which are classified into linear DNA probes, composite DNA nanomaterials and three-dimensional (3D) DNA nanostructures. We also highlight the future research directions in the field of APE1 activity imaging.

To activate gene expression, the initiation of transcription is a highly regulated process involving the interaction of proteins and DNA nucleotides at the promoter site, which consists of a small number of base pairs. As it involves interactions at the atomic scale, it is challenging to determine the mechanism of binding responsible for the great specificity between the amino acid residuals comprising the transcription binding protein and the DNA nucleotides comprising the promoter. Here, a new approach to characterize the transcription initiation process is developed and verified from analysis of comparative pharmacological efficacy data and elemental modeling. The newly developed description of a mechanism for transcription initiation involves the direct binding of small molecule ligands of approximately twenty carbon atoms, which are both structurally symmetric to DNA nucleotides, and also chemically complementary in its functional groups for interaction with the oxygen element at the carbon two position of thymine and with the phosphodiester chain. The results indicate that the activating ligands are transported to the DNA nucleotide promoter site by protein transcription factors, which serve as delivery vectors, for transfer of the ligand to the DNA nucleotide pairs. The ligands examined in this study include the steroid hormones, synthetic steroid molecules, derivatives of vitamin D, and prostaglandins, particularly PGJ2 and 15d-PGJ2. The transcription factors evaluated include glucocorticoid receptors, VDR, PPAR, and TBP. Through the developments, it is shown that because of the chemically complementary binding of the ligand to DNA nucleotide pairs, the resultant intermolecular complex produces three hydrogen bonds for the A-T and T-A configurations, which matches that of G-C and C-G. The orientation of the nucleotide base pairs is also seen to adjust as an inversion of the nominal position of the nucleobases to a dimer configuration presented via TBP transcription factor. The developments comprise a new approach to characterizing the initiation of the transcription process comprising the direct binding and interaction of ligands with DNA nucleotides as verified through comparative analysis of pharmacological activity and through perfect structural correspondence between the steroid hormone class as ligands with Watson-Crick DNA nucleotide pairings.

We apply hierarchical clustering (HC) of DNA k-mer counts on multiple Fastq files. The tree structures produced by HC may reflect experimental groups and thereby indicate experimental effects, but clustering of preparation groups indicates the presence of batch effects. Hence, HC of DNA k-mer counts may serve as an unspecific diagnostic device. In order to provide a simple applicable tool we implemented sequential analysis of Fastq reads with low memory usage in an R package (seqTools) available on Bioconductor. The approach is validated by analysis of Fastq file batches containing RNAseq data. Analysis of three Fastq batches downloaded from ArrayExpress indicated experimental effects. Analysis of RNAseq data from two cell types (dermal fibroblasts and Jurkat cells) sequenced in our facility indicate presence of batch effects. The observed batch effects were also present in reads mapped to the human genome and also in reads filtered for high quality (Phred > 30). We propose, that hierarchical clustering of DNA k-mer counts provides an unspecific diagnostic tool and a quality criterion and for RNAseq experiments.