ABSTRACT Objective To establish a better triage strategy using SOX1/PAX1 methylation detection for high‐risk HPV (hrHPV)‐positive women than cytology. Design A cohort study. Setting Population‐based cervical cancer (CC) screening cohort. Population A total of 5684 women were enrolled. Methods SOX1/PAX1 methylation was detected by quantitative methylation‐specific PCR using cytologic residue from hrHPV‐positive women at baseline in a 3‐year CC screening cohort. Risk stratification ability was evaluated by the immediate and cumulative cervical intraepithelial neoplasia (CIN) grade 2/3 or worse (CIN2+/3+) risks. Main Outcome Measures CIN3+ and CIN2+. Results At baseline, 682 hrHPV‐positive women were included with 63 CIN2+ and 39 CIN3+. Over 3 years, 109 CIN2+ and 62 CIN3+ were detected. Methylation demonstrated better risk stratification than cytology among hrHPV‐positive women. When compared with current practice triage strategy (Strategy A), post hoc re‐triage analysis showed that methylation triage for all hrHPV‐positive women (Strategy C) significantly increased sensitivity (97.44%/83.87% vs. 84.62%/64.52%, p = 0.0476/0.014), specificity (83.36%/85.00% vs. 73.41%/73.55%, p = < 0.001/< 0.001), positive predictive value (26.21%/35.86% vs. 16.18%/19.61%, p = 0.022/0.001), and negative predictive value (99.81%/98.14% vs. 98.74%/95.40%, p = 0.040/0.012) in detecting immediate and 3‐year cumulative CIN3+. Similar improvements were observed for methylation triaged for HR12‐positive (Strategy B) and for combined HPV and cytology primary screening (Strategy D). More importantly, all methylation‐based triage strategies reduced colposcopies and postponed follow‐up intervals compared to Strategy A over the 3‐year period of CC screening. Conclusion SOX1/PAX1 methylation showed better risk stratification compared with cytology and enabled more efficient management of HPV‐positive women, though external validation and head‐to‐head comparisons with other triage methods are needed.
Xie et al. (Mon,) studied this question.