DNA methylation marker for the triage of hrHPV positive women in cervical cancer screening: Real-world evidence in Taiwan

Chih Long Chang, Shih Chu Ho, Yee Fun Su, Yi Chen Juan, Chueh Yi Huang, An Shine Chao, Zen Shing Hsu, Chi Feng Chang, Chyng Wen Fwu*, Ting Chang Chang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

17 Scopus citations


Objective: Human papillomavirus (HPV) testing as the primary cervical cancer screening followed by reflex cytology if high-risk HPV is present (hrHPV+) is recently adopted in some countries. However, reflex cytology's sensitivity is variable, and a suitable triage approach for hrHPV+ remains controversial. Here, we compared the performance of three triage tools in hrHPV+ women. Methods: Three triage tools—cytology, HPV16/18 genotyping, and DNA methylation biomarker PAX1m—were analyzed for their clinical performance in hrHPV+ women. In addition, women without cervical cancer at enrollment were followed for histologically confirmed high-grade cervical intraepithelial neoplasia or worse (CIN3+) annually using Papanicolaou smear. Results: Of 4762 women aged ≥20 years enrolled, 502 (10.5%) were hrHPV+. PAX1m and cytology demonstrated similar accuracy (>90%), sensitivity (>78%), and specificity (>92%) as triage tools in 429 hrHPV+ women aged 30–64 years. PAX1m had better accuracy and specificity (91.6% and 92.5%, respectively) than HPV16/18 (76.9% and 76.8%, respectively). The incidence of CIN3+ among hrHPV+ women was 10.7 cases/1000 person-years. The incidence was significantly greater in PAX1m-positive women than in PAX1m-negative women. Conclusions: PAX1m has comparable clinical performance to cytology and better accuracy and specificity than HPV16/18 as the triage tool for detecting CIN3+ in hrHPV+ women. The PAX1m assay is thus a promising molecular-based triage tool for early detection of CIN and predicting disease progression in hrHPV+ women. It can be especially useful in countries where adequate cytology-based infrastructure is lacking, such as some Southeast Asian countries, for cervical cancer screening and prevention.

Original languageEnglish
Pages (from-to)429-435
Number of pages7
JournalGynecologic Oncology
Issue number2
StatePublished - 05 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 Elsevier Inc.


  • Cervical cancer
  • DNA methylation
  • HPV triage
  • PAX1
  • Screening


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