Evaluating PAX1 methylation for cervical cancer screening triage in non-16/18 hrHPV-positive women

Abstract Background In China, the national cervical cancer screening protocol involves initial testing for high-risk human papillomavirus (hrHPV), followed by cytology for hrHPV-positive cases. This study evaluates the effectiveness of PAX1 methylation (PAX1 m ) analysis in identifying precancerous or cancerous lesions in cervical samples from Chinese women positive for non-16/18 hrHPV strains. Methods Between February 2022 and March 2023, 281 cervical samples from non-16/18 hrHPV-positive women underwent cytological examination and PAX1 m analysis. The study assessed the statistical relationship between PAX1 m levels and the presence of cervical lesions, comparing the diagnostic performance of PAX1 m to conventional cytology. Results A significant association was found between PAX1 methylation levels and the risk of CIN2 + and CIN3 + lesions, with 47 instances of CIN2 + detected. Odds ratios (ORs) for moderate and high PAX1 m levels were 8.86 (95% CI: 2.24–42.17) and 166.32 (95% CI: 47.09-784.97), respectively. The area under the ROC curve for PAX1 m in identifying CIN2 + lesions was 0.948 (95% CI: 0.895–0.99). PAX1 m demonstrated similar sensitivity and negative predictive value (NPV) to cytology but reduced the colposcopy referral rate from 47.7% with cytology alone to 25.6% with PAX1 m , showing superior specificity and positive predictive value across age groups. Conclusions PAX1 methylation is a strong indicator of CIN2 + and CIN3 + risk, offering diagnostic performance comparable to cytology with the added benefit of reduced unnecessary colposcopy referrals. These findings support the use of PAX1 m analysis as a reliable tool for triaging non-16/18 hrHPV-positive women in outpatient settings.