Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Advances in DNA Methylation Testing For Triage and Followup of Cervical Precancer

Version 1 : Received: 30 October 2023 / Approved: 30 October 2023 / Online: 31 October 2023 (02:23:34 CET)

How to cite: Lorincz, A.T.; Wu, Q.; Lu, R.; Zhu, X. Advances in DNA Methylation Testing For Triage and Followup of Cervical Precancer. Preprints 2023, 2023101954. https://doi.org/10.20944/preprints202310.1954.v1 Lorincz, A.T.; Wu, Q.; Lu, R.; Zhu, X. Advances in DNA Methylation Testing For Triage and Followup of Cervical Precancer. Preprints 2023, 2023101954. https://doi.org/10.20944/preprints202310.1954.v1

Abstract

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.

Keywords

HPV; DNA methylation; cytology; cervical cancer; triage; biomarkers

Subject

Medicine and Pharmacology, Obstetrics and Gynaecology

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