Evaluation of a methylation classifier for predicting pre-cancer lesion among women with abnormal results between HPV16/18 and cytology.

BACKGROUND: Although HPV testing and cytology detection are successful for cervical screening in China, additional procedures are urgently required to avoid misdiagnosis and overtreatment. In this multicenter study, we collected cervical samples during screening in clinics. A total of 588 women with HPV16/18+ and/or cytology result ≥HSIL+ (high-grade squamous intraepithelial lesion or worse) were referred to colposcopy for pathological diagnosis. Methylation of S5 was quantified by pyrosequencing.

RESULTS: The S5 classifier separates women with ≥HSIL+ from <HSIL with a high area under the curve (AUC) of 0.86 (95% CI 0.840-0.910). The cutoff of 2.85 was conducted in our study. Remarkably, all cancer cases (n = 67) were detected by S5. The sensitivity of S5 for "≥HSIL+" was 89.1% (95% CI 86.2-92.4%), and the specificity was 76.6% (95% CI 72.2-78.9%). S5 could reduce unnecessary colposcopy referrals by 74% (95% CI 71.3-78.1%) with virtually no loss of sensitivity for HSIL+, and the follow-up data support the utility of the S5 classifier.

CONCLUSION: The S5 classifier with high sensitivity and specificity provided increasing diagnostic information for women with HPV16/18+ and/or cytology results and could reduce the numerous unnecessary colposcopy referrals and avoid overtreatment.