Triage performance of DNA methylation for women with high-risk human papillomavirus infection - abstract & key findings

Q: What is the objective of this study?

To validate the triage performance of cytological DNA methylation for detecting CIN3+ in women with hrHPV infection from a large prospective cohort (METHY3).

Q: What were the key findings about specificity and referral reduction?

PAX1m/JAM3m(+) showed the highest specificity for CIN3+ (89.6%). Compared with HPV16/18 genotyping and LBC, PAX1m/JAM3m testing reduced referrals to colposcopy by 20.64 and 61.18 percentage points, respectively.

Sep 24, 2026

Uploaded by Taylor Morgan

DNA methylation is evaluated as a cervical cancer screening biomarker by validating the triage performance of cytological DNA methylation for detecting CIN3+ among women with high-risk human papillomavirus (hrHPV) infection. The study compared triage performance using HPV16/18 genotyping, liquid-based cytology (LBC), and PAX1/JAM3 methylation (PAX1m/JAM3m) against definitive cervical histology. Among 4,394 hrHPV-infected women, 1,105 with definitive histological outcomes were analyzed.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Abstract

Objective

Methods

Results

Conclusions

Implications for practice

Introduction

Triage performance of DNA methylation for women with high-risk human papillomavirus infection Linghua Kong1,2,3, Xiaoping Xiao1,2,3, Huanwen Wu4, Yan You4, Xitong Jin5, Yuligh Liou5,6, Pei Liu5, Jinghe Lang1,2,3, Lei Li*, 1,2,3, 1Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing 100730, People’s Republic of China, 2 National Clinical Research Center for Obstetric & Gynecologic Diseases, Beijing 100730, People’s Republic of China, 3State Key Laboratory for Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing 100730, People’s Republic of China, 4Department of Pathology, Peking Union Medical College Hospital, Beijing 100730, People’s Republic of China, 5Department of Medical Laboratory, Beijing Origin-Poly Bio-Tec Co., Ltd., Beijing 102600, People’s Republic of China, 6Clinical Precision Medicine Research Center, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510062, People’s Republic of China *Corresponding author: Lei Li, MD, Shuaifuyuan No. 1, Dongcheng District, Beijing 100730, People’s Republic of China ([lileigh@163.com](lileigh@163.com)) . Abstract Objective: DNA methylation is a promising biomarker for cervical cancer screening. This study aimed to validate the triage performance of cytological DNA methylation for detecting cervical intraepithelial neoplasia of grade 3 or worse (CIN3+) in women with high-risk human papillomavirus (hrHPV) infection from a large prospective cohort undergoing opportunistic screening in China (METHY3) . Methods: The triage performance for detecting CIN3+ lesions was compared between HPV16/18 genotyping, a liquid-based cytology (LBC) test, and the PAX1 and JAM3 methylation ( PAX1m/JAM3m) test according to cervical pathologic outcomes. Among the 4394 women infected with hrHPV, 1105 had definitive cervical histological findings that were analyzed. Results: For detecting CIN3+, the specificity of HPV16/18(+), the LBC result of ≥atypical squamous cells of undetermined significance (ASCUS), and PAX1m/JAM3m(+) was 66.4%, 23.9%, and 89.6%, respectively, with odds ratios of 4.24 (95% confidence interval [CI], 2.85-6.40), 4.44 (2 .27-10. 1), and 18.5 (12 .1-28.7) ( P < .001), respectively. PAX1m/JAM3m(+) had the highest area under the receiver operating characteristic curve (0 .790, 95% CI, 0.747-0.832) in the whole cohort and in women of various ages. PAX1m/JAM3m (+) was detected in all patients with cancer (n = 28) . Compared with HPV16/18 genotyping and the LBC test, PAX1m/JAM3m testing reduced referrals to colposcopy by 20.64 percentage points and 61.18 percentage points, respectively. Conclusions: PAX1m/JAM3m testing is highly specific for detecting CIN3+ . As a triage biomarker, it is superior to HPV 16/18 genotyping and LBC testing for women with hrHPV infection. Keywords: cervical screening; DNA methylation; CIN3; HPV genotype; cytology test. Implications for practice The gene of PAX1/JAM3 methylation test significantly increased the specificity of screening CIN3+ in women with minimally abnormal cytological results, especially in younger women. Introduction Primary human papillomavirus (HPV) testing is increasingly regarded as the preferred approach for cervical cancer screening.1,2 HPV-based cervical screening is highly sensitive and objective for detecting high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer, but its specificity is suboptimal.3 Most women infected with HPV experience a transient infection that resolves naturally4; therefore, many colposcopy referrals and associated cervical excisional treatments are unnecessary and could be reduced with better triage tests. The use of a liquid-based cytology (LBC) test and/ or HPV 16/18 genotyping is recommended as an additional triage test to identify women who require further investigation.5 Unfortunately, these methods are not specific enough,6 and in many settings, trained cytologists ar

FAQs

What is the objective of this study?

To validate the triage performance of cytological DNA methylation for detecting CIN3+ in women with hrHPV infection from a large prospective cohort (METHY3).

Which triage tests were compared for detecting CIN3+?

HPV16/18 genotyping, a liquid-based cytology (LBC) test, and the PAX1 and JAM3 methylation (PAX1m/JAM3m) test were compared using cervical pathological outcomes.

What were the key findings about specificity and referral reduction?

PAX1m/JAM3m(+) showed the highest specificity for CIN3+ (89.6%). Compared with HPV16/18 genotyping and LBC, PAX1m/JAM3m testing reduced referrals to colposcopy by 20.64 and 61.18 percentage points, respectively.

Sep 24, 2026

Uploaded by Taylor Morgan