Evaluation of Host Gene Methylation as a Triage Test for HPV–Positive Women—A Cohort Study

Abstract Objectives This study was designed to evaluate the performance of a host gene methylation marker panel (ASTN1, DLX1, ITGA4, RXFP3, SOX17, and ZNF671) in the triage of human papillomavirus (HPV)-positive women, its possible impact in a cervical cancer screening program, and the possible influence of the variation of the rate of HPV16/18 in its performance. Materials and Methods Cohort study in which consecutive women referred for colposcopy in an organized cervical cancer screening program had repeated HPV testing, colposcopy, and biopsies. The women that remained HPV positive at the time of colposcopy were tested with the panel of DNA methylation markers. The performance of the test was evaluated and compared to standard practice. Results The study test had a sensitivity and specificity for cervical intraepithelial neoplasia (CIN) 2+ of 60.8% (49.1–71.6%) and 88.4% (83.2–92.5%), respectively. For CIN3+, it was of 78.0% (64.0–88.5%) and 86.0% (80.8–90.2%), respectively. The rate and level of methylation positively correlated with the severity of disease. The use of methylation reduces the referral for colposcopy to 25.5%, while detecting 78.0% of the CIN3+ cases. Referral of all HPV16/18-positive cases and triage of the other high-risk HPV-positive cases with methylation, detects 90.0% of the cases of CIN3+, while reducing the number of referrals to 43.2%. The variation in the rate of HPV16/18 does not relevantly affect the performance of the methylation panel. Conclusions The studied methylation panel has a high sensitivity and specificity for CIN3+ and reduces the rate of referrals for colposcopy, without relevant variation according to the rate of HPV16/18.