Improving Accessibility of Cervical Cancer Screening: A Global Perspective on Self-Sampling and Digital Innovation

1. Introduction

FemTech represents a rapidly evolving sector of technology-driven solutions transforming cervical cancer prevention through Artificial Intelligence (AI) enabled diagnostics, smart self-sampling devices, and integrated digital platforms [1,2]. This review evaluates emerging self-sampling technologies and FemTech solutions for cervical cancer screening, analysing innovations and performance metrics, implementation strategies, and cost-effectiveness considerations for resource-limited settings.

Human Papillomavirus (HPV) infection is extremely common, with an estimated 80% of sexually active people acquiring at least one HPV type during their lifetime [3,4]. While most infections clear naturally within two years, persistent infection with high-risk HPV types causes 99.7% of cervical cancer cases, making HPV detection an important screening strategy [5,6]. In 2022, there were 660,000 new diagnoses and 350,000 from cervical cancer deaths globally [7,8].

This preventable disease disproportionately affects LMICs, which account for 90% of cervical cancer mortality [9,10,11]. The burden varies significantly by region, with age-standardised incidence rates ranging from 75 cases per 100,000 women in some African countries to less than 10 per 100,000 in many high-income countries [11]. The risk of persistent infection and progression to cancer is higher in people with compromised immune systems, particularly those living with HIV who are 6 times more likely to develop cervical cancer [12]. These disparities reflect inequitable access to both HPV vaccination and screening programmes [13,14].

The United Kingdom’s experience illustrates both progress and persistent challenges in cervical cancer control. While comprehensive screening programs contributed to a 25% decrease in incidence rates since the early 1990s, recent data show a 4% increase over the past decade suggesting evolving risk factors and potential gaps in screening coverage [15,16]. This trend has been exacerbated by the COVID-19 disruptions, with screening participation declining significantly. Some areas of London now report screening uptake rates as low as 48%, reflecting widespread disengagement with screening services [17,18].

Screening detects asymptomatic precancerous lesions which if undetected and untreated, can put women at risk of developing cervical cancer. In 2023, the NHS announced a plan for cervical cancer elimination by 2040 (defined as fewer than 4 cases per 100,000 women) which aligns with the World Health Organization (WHO) global 90-70-90 initiative, which aims for 90% HPV vaccination coverage, 70% screening coverage, and 90% treatment of precancerous lesions by 2030 [9,19]. Achieving this goal requires enhanced HPV vaccination coverage, increased screening participation, and innovative solutions adaptable to diverse healthcare settings [20,21,22,23,24]. Scotland demonstrates the potential success of comprehensive prevention strategies, achieving near elimination through high vaccination uptake and effective screening programmes [25]. The prevention of cervical cancer stands at a critical transition point. While HPV vaccination programmes are widespread in high income countries, their full impact on mortality rates will take decades to realise due to the extended latency between infection and cancer development [26,27]. Meanwhile, the evolution from traditional cytology to HPV-based screening (see Figure 1) offers enhanced detection capabilities, though implementation challenges persist, especially in resource-limited settings [28,29].

1.1. Prevention Strategies

1.1.1. Primary Prevention

HPV vaccination demonstrates exceptional efficacy, with the Swedish nationwide study (1.7 million women) showing a 90% reduction in cervical cancer incidence among girls vaccinated before age 17 over 2006-2017 [30]. Norwegian registry data showed 82% reduction in CIN2+ in girls vaccinated at an early age [31]. Effectiveness significantly decreases when vaccination is given after age 17 [32]. A systematic review from 2023 demonstrated vaccine effectiveness ranging from 74-93% for ages 9-14 versus 12-90% for ages 15-18, highlighting the critical importance of vaccination at an early age [33]. The implementation of WHO’s 90% vaccination coverage strategy poses significant challenges in LMICs due to infrastructure limitations and cost barriers [34,35]. Historical controversies surrounding vaccine trials and implementation programmes have created enduring trust issues in some regions, particularly in India and Sub-Saharan Africa [36]. These challenges underscore the importance of ethical implementation practices, community engagement, and cultural sensitivity in vaccination programmes.

1.1.2. Secondary Prevention

The evolution of screening methods marks a significant advancement in cervical cancer prevention, transitioning from traditional cytology to HPV-based approaches [37,38]. While high-income countries maintain screening coverage above 60%, LMICs struggle with rates as low as 20%, highlighting the need for resource-appropriate solutions [39]. Secondary prevention through HPV testing has emerged as superior to cytology for cervical screening; extensive research demonstrates enhanced sensitivity compared to cytology-based approaches [40,41].

1.1.3. Emerging Technologies

WHO’s 2021 guidelines recommended HPV DNA testing as the preferred screening method for women aged 30-49 years, with 5–10-year intervals [42]. Implementation success varies globally, requiring careful consideration of local healthcare infrastructure, resource availability, population-specific needs and healthcare system capacity [6,43].

Self-sampling represents a transformative approach to cervical cancer screening, particularly for underserved populations at elevated risk of HPV infection [44,45]. This review examines how innovative technologies and implementation strategies can bridge disparities in screening access. We analyse the potential of self-sampling and FemTech solutions to overcome traditional barriers, with particular focus on their application in resource-limited settings where conventional screening methods remain challenging to implement.

2. Understanding HPV and Cervical Carcinogenesis: A Foundation for Prevention

Understanding the relationship between HPV infection and cervical cancer development is crucial for developing effective prevention strategies and implementing appropriate screening programs [6,46,47]. Persistent infection with high-risk HPV is the primary causative agent of cervical cancer, with high-risk types 16 and 18 responsible for approximately 70% of cases globally, while types 31, 33, 45, 52, and 58 contribute another 20% [48,49]. The global prevalence of HPV16 and HPV18 in women with normal cytology is 3.2% and 1.4%, respectively [50,51].

HPV causes cervical cancer through persistent infection of epithelial cells, where continued expression of the viral oncoproteins E6 and E7 disrupt cell cycle regulation, leading to genomic instability and malignant transformation [52,53]. This process can result in precancerous lesions, graded as Cervical Intraepithelial Neoplasia (CIN1-3), with CIN2/3 requiring treatment to prevent progression to cancer [54,55]. Early detection through screening and colposcopy examination is crucial for identifying and managing CIN [56].

2.1. HPV Vaccination

Prophylactic HPV vaccines have demonstrated efficacy, achieving up to 90% reduction in vaccine-type HPV infections and 85% reduction in high-grade cervical lesions among vaccinated cohorts aged 13-24 years [57]. Evidence suggests extending screening intervals for vaccinated populations, with recommendations to start screening at age 30 instead of 25 for vaccinated women [58]. However, even the broadest 9-valent vaccine does not protect against all oncogenic HPV types, necessitating continued screening programs [59,60].While vaccination coverage is increasing globally, uptake remains suboptimal in many regions, and women aged 35 and older, who were not eligible for vaccination programs, remain at risk and require regular screening [61,62].

Recent evidence supports WHO’s simplified HPV vaccination schedules: one dose for ages 9-14 years, one or two doses for ages 15-20 years, and two doses for those over 21 years. This optimisation reduces costs by 30% while maintaining efficacy in younger age groups [63,64].

Global vaccination rates declined significantly, with studies showing coverage reductions of 42% in Italy and decreased uptake from 89.92% to 69.59% during the pandemic in US border communities [65]. These disruptions are projected to increase cases of cervical cancer and precancerous lesions over the coming decades, necessitating urgent recovery strategies [66].

2.2. Evolution of Cervical Cancer Screening Methods

The transition from traditional cytology to HPV-based screening represents a significant advancement in cervical cancer detection. HPV testing demonstrates superior detection of precancerous lesions with 98.1% sensitivity (95% CI: 96.3-96.7) for CIN3+, compared to cytology’s 48.5% sensitivity (95% CI: 44.0-53.0) [67]. While HPV testing shows slightly lower specificity (94.4%, 95% CI: 94.1-94.7) than cytology (97.9%, 95% CI: 97.8-98.1), new molecular technologies offer improved specificity without compromising sensitivity [67].

Emerging molecular approaches such as mRNA-based tests specifically detect active HPV infections by identifying viral oncogene expression, reducing false positives from transient infections [68]. Next-generation sequencing platforms enable simultaneous detection of multiple biomarkers, allowing better risk stratification of HPV-positive women. These innovations help identify women most at risk of disease progression while reducing unnecessary referrals [69].

2.4. Innovative Vaccination and Screening Approaches in High-Income Countries

High-income countries have pioneered different approaches to implementing HPV-based screening and self-sampling programs, providing valuable insights for global cervical cancer prevention strategies. Australia and the UK demonstrate successful integration of vaccination and screening programs. Australia’s comprehensive approach, achieving 80% vaccination coverage and implementing primary HPV screening, projects cervical cancer elimination by 2028, with 92% reduction in high-grade abnormalities among women vaccinated before age 15 [26,70]. The UK’s strategy complements its screening programme, contributing to a 25% decrease in cervical cancer incidence since the 1990s [71].

European countries have led self-sampling innovations. The opt-in model in the Netherlands achieved 16% self-sampling uptake by 2020, while Sweden’s direct-mailing approach during COVID-19 increased coverage from 54% to 60% in one year, reaching Europe’s highest rate of 83% [72,73]. Both countries maintain sustained screening coverage above 70% through automated testing platforms and standardised protocols, particularly benefiting under-screened populations [72,73].

2.5. Prevention Strategies in Middle and Low-Income Countries

Middle-income countries have developed effective hybrid approaches to cervical cancer prevention, exemplified by Malaysia and Thailand’s integration of national vaccination programs with phased HPV-based screening implementation [74]. These programs achieve 85-90% vaccination coverage through school-based delivery systems while expanding screening access via public-private partnerships [75].

WHO’s pragmatic approach for LMICs focuses on high-precision HPV testing with two lifetime screens at ages 35 and 45, balancing effective coverage against resource constraints [76]. Rwanda’s successful implementation demonstrates the potential of this approach, achieving 93% HPV vaccination coverage among girls aged 11-12 and screening 329,000 women between 2013-2016, resulting in a 50% reduction in cervical cancer mortality [77].

Successful programs utilise community health worker networks, mobile clinics, and partnerships with local religious leaders while integrating self-sampling options to optimise resource utilisation [78]. This comprehensive approach enables LMICs to maximise precancerous lesion detection during peak risk periods while maintaining cost-effectiveness within resource-limited healthcare systems [74].

3. Implementation Barriers and Economic Impact of Cervical Screening in LMICs

The implementation of cervical cancer prevention programs in low- and middle-income countries faces significant systemic challenges that impact both healthcare delivery and economic outcomes. A WHO analysis (2022) of 45 African countries revealed only 15% have universal health coverage schemes for cervical cancer screening, resulting in significant out-of-pocket expenditure for families [79]. Screening rates in LMICs remain critically low at 5%, exemplified by Nigeria where only 8.7% of 60.9 million at-risk women undergo screening, with even lower rates in rural areas [80].

The economic implications are substantial yet promising: every dollar invested in cervical cancer prevention yields a $3.20 return through improved health outcomes and productivity gains [81]. HPV-based screening programs demonstrate high cost-effectiveness, with an incremental cost-effectiveness ratio of $569 per quality-adjusted life year gained [82].

3.1. Innovative Implementation Strategies in LMICs

Several countries have developed effective solutions to increase screening coverage through innovative integration with existing healthcare services and novel delivery approaches. Rwanda has successfully integrated cervical screening with HIV/AIDS care services, with studies showing increased screening rates among HIV-positive women through integrated services [77]. Ethiopia’s screening coverage remains very low at less than 2% nationally, while Zambia has achieved about 26% population-level coverage through HIV program integration [83,84]. Mobile screening units and task-shifting strategies have been implemented in Rwanda to reach women in remote areas, with the country screening nearly 95,000 women and achieving 91% treatment rates for those testing positive [85].

International support has been crucial, with Gavi, The Vaccine Alliance committing $600 million for HPV vaccination and the Global Fund reaching over 1 million women through integrated HIV-screening programmes [86]. While many LMICs currently rely on visual inspection methods – direct inspection of the cervix to identify macroscopic morphological abnormalities, with typically low specificity - (Visual inspection with acetic acid ((VIA))/Visual inspection with Lugol’s Iodine ((VILI))) due to resource constraints, these approaches offer advantages of immediate results and same-day treatment [87]. The emergence of HPV self-sampling technologies presents an opportunity to implement more sensitive molecular testing while maintaining community-based screening benefits, which in some setting will be followed up by VIA/VILI and in some contexts referral to colposcopy (depending on the infrastructure available, based on country).

4. Enhancing Screening Participation Through Self-Sampling: Evidence and Implementation

Self-sampling represents a transformative approach to cervical cancer screening, addressing traditional barriers while improving accessibility for underserved populations through patient-centred collection methods. Cervical screening coverage in England has declined, with only 69.9-71.2% of eligible women screened within the recommended interval [88,89]. Barriers to screening include discomfort, embarrassment, time constraints, and procedure-related anxiety [90]. Lower uptake is associated with younger age, ethnic minority background, and socioeconomic deprivation [91]. Women who have experienced sexual abuse are less likely to attend screening [92]. Studies show that transgender men and non-binary people have significantly lower cervical screening uptake, with only 58% of those eligible having been screened [93]. Research indicates that transgender men are 37% less likely to be current with cervical screening compared to cisgender patients, and are ten times more likely to have inadequate test results [94].

The YouScreen trial in London (n=8338) validated self-sampling’s effectiveness in increasing participation, achieving 56% uptake through GP practices compared to 13% via direct mailing. The approach showed particular success among ethnic minorities (64% coverage) and socioeconomically deprived populations (60% coverage)[95].

Implementation strategies for self-sampling vary in effectiveness, with community-based distribution through pharmacies and health centres achieving higher uptake (20-35%) compared to direct mailing methods (8-25%) [95]. The UK HPValidate study validated multiple device-test combinations (3 different collection devices: Evalyn Brush (Rovers Medical), Self-Vaginal Floqswabs (Copan) and Aptima Multitest (Hologic), demonstrating strong user preference (85%) for having self-sampling as an option alongside traditional screening [96].

Economic analyses demonstrate cost-effectiveness of self-sampling in low-resource settings. A 2023 study in Sikkim, India found that HPV self-testing cost US$15.3 per woman screened compared to US$19.2 for traditional screening, representing a significant cost reduction [97].

Successful implementation in LMICs requires tailored delivery approaches combining clinic-based and home-based methods. Community health workers facilitate education and sample collection through door-to-door visits, while trusted community leaders address health literacy through visual instructions [97]. Sample transport systems using swabs remain stable at room temperature for up to two weeks, eliminating cold-chain requirements [98]. Digital platforms enable result communication where infrastructure permits, as demonstrated by the PRESCRIP-TEC project across Bangladesh, India, Uganda and Slovakia [99].

Self-sampling is endorsed by WHO because of its potential to increase screening coverage among underserved populations, though success depends on standardised procedures, comprehensive follow-up protocols, and context-specific implementation strategies that consider local healthcare infrastructure and economic conditions [45].

5. Evolution and Performance of Self-Sampling Technologies in Cervical Screening

The development of self-sampling technologies represents a significant advancement in cervical cancer screening, with various collection methods demonstrating increasing accuracy and accessibility while addressing traditional barriers to participation [100]. Collection approaches have evolved to encompass vaginal swabs with soft, flexible tips made of cotton, polyester, or nylon fibres; brushes designed with flexible low-density polyethylene (LDPE) bristles for standardised sampling; and diagnostic tampons utilising absorbent materials to collect vaginal secretions [101,102]. Additional innovations include urine collection devices targeting first-void samples and menstrual fluid collection systems like Qvin-pad and the Papcup [103,104]. These diverse sampling methods offer specific advantages and performance characteristics suited to different healthcare settings and patient populations, enabling more inclusive screening options across varied contexts.

Performance metrics from meta-analyses show that self-collected samples have slightly lower detection rates compared to clinician collection, with sensitivity reduced by 14% (95% CI: 9-20%) and specificity by 11% (95% CI: 8-15%) [105]. However, newer PCR-based assays demonstrate comparable accuracy, particularly with lavage devices and brushes [105].

The integration of AI enhances screening precision through advanced image analysis capabilities. Recent studies demonstrate AI algorithms achieving sensitivity and specificity ranges of 0.22-0.93 and 0.67-0.95 respectively in classifying visual inspection images [106,107]. Wu et al. (2024) highlight how AI-assisted digital microscopy platforms like CytoBrain can analyse digitised cervical samples with up to 78% efficiency in cell classification, reducing reliance on specialised personnel while maintaining diagnostic accuracy [108]. While these technologies show particular promise for resource-limited settings, large-scale validation in real-world conditions remains crucial for establishing clinical feasibility.

Recent advancements in point-of-care (POC) HPV testing offer promising solutions for cervical cancer screening in resource-limited settings. These tests aim to provide rapid results with high sensitivity and specificity, addressing barriers in traditional cytology-based screening [109,110]. The careHPV test demonstrates good performance, with sensitivity and specificity around 88% and 84% for CIN2+ detection [111]. New technologies like isothermal amplification and lateral flow detection enable low-cost, sample-to-answer HPV testing suitable for decentralised screening [20]. HPV-based screen-and-treat approaches have shown effectiveness in reducing cervical disease and over-treatment compared to visual inspection methods [112]. A study in Papua New Guinea found high acceptability and safety of an integrated POC HPV self-sampling and same-day treatment strategy. POC innovations are transforming screening accessibility in resource-limited settings [113]. The Hemex Health Gazelle platform demonstrates the potential for rapid, affordable testing with high accuracy, achieving results within 8 minutes while maintaining laboratory-grade standards [114].

WHO has recently launched updated target product profiles for POC tests, emphasising the need for affordable, user-friendly devices suitable for low-resource settings [115]. These profiles aim to guide manufacturers in developing tests that meet specific performance and operational characteristics crucial for effective cervical cancer screening in diverse healthcare contexts [115].

5.1. Device Types and Clinical Performance

The Evalyn^® Brush and FLOQSwabs™ (Copan) represent extensively validated self-sampling methods, with the Evalyn^® Brush achieving 97% user acceptability through innovative features like depth indicators and click mechanisms [121,128]. FLOQSwabs™ use short nylon fibres arranged on a solid plastic shaft. The fibres are positioned perpendicularly to promote strong capillary action, allowing for rapid absorption of liquid samples. Also because it lacks an internal core, more than 90% of the collected sample can be easily released into testing media. While urine-based testing offers minimal invasiveness and potential integration with other screening programs, it demonstrates lower sensitivity (51-63%) compared to other self-sampling methods, limiting its current utility as a primary screening approach [129].

Table 1. provides a comprehensive comparison of current self-sampling devices, highlighting key features: [92,116–127].

The Daye Diagnostic Tampon (DT) shows promising performance with 82.9% sensitivity and 91.6% specificity, achieving the highest valid result rates (99.2%) compared to vaginal self-swabs (95.4%) and clinician-collected samples (90.8%) [123]. User acceptance is high, with 78.3% reporting high comfort pre-sampling and 74.5% finding it “very easy” to use [123,130]. When collected first in the sampling sequence, the DT achieves optimal performance (100% sensitivity, 96.8% specificity), with 70.5% of participants preferring this method [123].

Teal Health was granted Breakthrough Device Designation by FDA in 2024 [131]. It has integrated digital features, including visualisation capabilities and automated sample verification, achieving 94% sample adequacy rates and higher user satisfaction (Stanford Medicine Innovation Report, 2023). The Papcup system offers HPV detection from menstrual blood samples, providing results within 15 minutes and improving accessibility for younger women while maintaining functionality for post-menopausal women through traditional swab collection [132]. A novel approach using a modified menstrual pad (Q-Pad) for passive HPV sample collection showed high concordance (95-100%) with clinician-collected samples among HPV-positive women, offering potential for integration into cervical cancer prevention programs [125].

A collection of studies examined the effectiveness of self-sampling methods for HPV testing compared to clinician-taken cervical samples. Vaginal self-sampling using dry flocked swabs, wet dacron swabs, and urine samples showed similar sensitivity and specificity to clinician-taken samples for detecting high-grade cervical lesions [92,133,134]. Self-sampling methods were generally well-accepted by women, with urine collection being the easiest and most preferred option [92].

Digital health solutions demonstrate significant benefits in cervical cancer screening programmes, with electronic health interventions improving screening participation rates by 46% compared to usual care, with particularly strong impact in LMIC settings [135]. However, a critical limitation is the requirement for additional cytology visits following HPV-positive results, leading to 35-45% patient dropout rates during follow-up [136]. While newer devices attempt dual sample collection for both HPV and cytology testing, cytological examination from self-collected samples shows lower adequacy rates compared to clinician collection, primarily due to their inability to sample the cervical transformation zone where precancerous lesions typically originate [137]. Studies comparing self-sampling cytology to clinician collection show sensitivity ranges of 64.7-71.9% and specificity of 81.0-86.6% for detecting intraepithelial lesions [138]. Current self-sampling devices cannot access the endocervical cells in the transformation zone - a capability that requires speculum examination in a clinical setting - limiting their utility for comprehensive cervical screening [138,139].

5.2. Advancements in DNA Methylation Testing

Recent advancements in DNA methylation testing represent a significant breakthrough in cervical cancer screening strategies. Meta-analyses demonstrate that DNA methylation markers achieve 63% sensitivity and 76% specificity for CIN2+, and 71% sensitivity and 75% specificity for CIN3+ [140]. This approach effectively identifies women at higher risk of progression to cancer while reducing unnecessary referrals. The WID-qCIN test, which assesses methylation of DPP6, RALYL, and GSX1 genes, demonstrated improved performance over cytology in a large real-world cohort [141]. While methylation assays initially require higher investment in molecular infrastructure, their superior sensitivity (63-71% for CIN2+/CIN3+) and reduced need for specialised cytology expertise make them potentially cost-effective for LMICs in the long term [142]. There is the potential to repurpose Covid testing PCR equipment which is universally available, reducing investment costs in DNA methylationSelf-sampling in combination with DNA methylation testing presents a promising pathway for cervical cancer screening evolution, potentially streamlining the screening process by eliminating separate cytology testing and reducing reliance on clinical infrastructure while maintaining high diagnostic standards.

HPV genotyping provides another effective triage strategy, already implemented in countries like the Netherlands. This approach allows risk stratification of HPV-positive self-samples based on type-specific risk, though implementation in LMICs requires consideration of cost and laboratory infrastructure. Studies show that genotyping can effectively identify women requiring immediate colposcopy versus those suitable for routine screening intervals [143,144].

Successful implementation requires careful consideration of quality assurance, healthcare integration, and cost analysis. This innovative combination of self-sampling, methylation testing, and POC analysis represents a potentially transformative approach to cervical cancer screening, aligned with WHO’s elimination goals, and could significantly improve screening accessibility and effectiveness in low-resource settings while maintaining high diagnostic standards.

6. Conclusions

The landscape of cervical cancer prevention is transforming through emerging technologies and evolving healthcare strategies. While progress has been made, substantial disparities persist between high-income countries and LMICs, necessitating innovative solutions.

Self-sampling technologies, including novel approaches like the Diagnostic Tampon, and the Teal Wand, show promise for increasing screening accessibility. Meta-analyses demonstrate that self-sampling can increase participation by 1.5 to 2.5 times compared to traditional methods, particularly impacting underserved populations [145,146].

The integration of AI and molecular testing enhances screening precision, with AI algorithms demonstrating 95% accuracy in identifying cervical abnormalities [147]. POC testing, showing 93% sensitivity and 91% specificity, offers potential solutions for resource-limited settings [148].

Cost-effectiveness analyses indicate that integrated digital health solutions can reduce screening costs by 46% in low-resource settings while improving follow-up rates [135]. However, successful implementation requires careful consideration of quality assurance, follow-up pathways, healthcare infrastructure integration, and cultural acceptability.

As HPV vaccination coverage increases globally, screening protocols will require adjustment, with evidence suggesting extended intervals for vaccinated populations [58]. Critical knowledge gaps require focused research, including standardised quality metrics for sample adequacy and evidence-based risk-stratification algorithms. Research priorities vary by healthcare setting, with high-income countries focusing on AI integration and multi-cancer detection platforms, while LMICs require cost-effective sample transport systems and POC testing validation.

The goal of cervical cancer elimination appears increasingly achievable through these innovative approaches, but success depends on addressing implementation challenges, particularly in resource-limited settings.