PAX1 methylation for triage of HR-HPV-positive women: a comparative analysis with cytology and HPV16/18 genotyping.

OBJECTIVE

To evaluate PAX1 hypermethylation (PAX1m) as a triage strategy test for cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in high-risk human papillomavirus (HR-HPV)-positive women versus liquid-based cytology (LBC) and HPV16/18 genotyping.

METHODS

This prospective, diagnostic accuracy study enrolled 1,461 h-HPV-positive women. All underwent colposcopy and biopsy. Triage strategies (PAX1m, LBC [ASC-US+], HPV16/18, combinations) were assessed against histology.

RESULTS

PAX1m test exhibited comparable sensitivity (90.1% vs. 94.4%, P = 0.366) but significantly higher specificity (77.2% vs. 18.6%, P < 0.001) than LBC for detecting CIN3+. Combined strategies showed performance: the HPV16/18 + PAX1m test achieved the highest specificity at 64.1% and 2.16 times higher positive predictive value (PPV) than HPV16/18 or LBC. PAX1m and HPV16/18 + PAX1m test achieved the area under the receiver operator characteristic (ROC) curves (AUC) for CIN3 + lesions with 0.837 and 0.792, respectively. The PAX1m test alone had the highest positive likelihood ratio (LR + = 3.95) and PPV (16.8%). Colposcopy referral rates were reduced to 26.1% (95% CI: 23.9%-28.4%) with PAX1m test and 38.7% (95%CI: 36.3%-41.3%) with HPV16/18 + PAX1m test compared to LBC at 82.1% (95%CI: 80.0%-83.9%). No cervical cancer cases were missed by PAX1m test.

CONCLUSION

The PAX1m test demonstrated favorable specificity compared to cytology in this cohort, though its CIN3 + sensitivity was slightly lower. This approach may offer an adjunctive strategy for resource-limited settings, though prospective validation in screening populations is needed.

TRIAL REGISTRATION: Not available.