The triage role of cytological DNA methylation in women with non-16/18, specifically genotyping high-risk HPV infection

Abstract Objectives To evaluate cytological DNA methylation testing methods for risk stratification in women with non-16/18 HPV, focusing on high-risk HPV (hrHPV) genotyping. Methods This study compared the triage performance of liquid-based cytology (LBC) testing, hrHPV genotyping, and PAX1 / JAM3 gene methylation (CISCER) testing. The absolute risks of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), grade 3 or worse (CIN3+), and colposcopy referral rates were calculated. Results The CISCER test showed a CIN3+ risk of 39.1% for positive and 0.9% for negative results. In comparison, LBC ≥ ASCUS and HPV33/35 genotyping had CIN3+ risks of 9.8% and 19.3%, respectively, for positive result. The colposcopy referral rates were 17.4% for CISCER+, 61.9% for LBC ≥ ASCUS, and 8.9% for HPV33/35+ genotyping. The CIN3+ risks were 40.0% and 50.0% when CISCER+ was combined with LBC ≥ ASCUS and HPV33/35+, respectively. The CIN3+ risks were 0.0% and 1.0% when CISCER- was combined with LBC with no intraepithelial lesions or malignancy (NILM) and non-HPV33/35, respectively. Our analysis of CIN2+ patients yielded similar results. Conclusions DNA methylation testing outperformed LBC in triaging women with non-16/18 hrHPV infections, significantly reducing unnecessary colposcopy referrals, particularly when combined with HPV33/35 genotyping.