Objective <p>To evaluate <i>PAX1</i> hypermethylation (<i>PAX1</i>^<i>m</i>) 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.</p> Methods <p>This prospective, diagnostic accuracy study enrolled 1,461&#xa0;h-HPV-positive women. All underwent colposcopy and biopsy. Triage strategies (<i>PAX1</i>^<i>m</i>, LBC [ASC-US+], HPV16/18, combinations) were assessed against histology.</p> Results <p><i>PAX1</i>^<i>m</i> test exhibited comparable sensitivity (90.1% vs. 94.4%, <i>P</i> = 0.366) but significantly higher specificity (77.2% vs. 18.6%, <i>P</i> &lt; 0.001) than LBC for detecting CIN3+. Combined strategies showed performance: the HPV16/18 + <i>PAX1</i>^<i>m</i> test achieved the highest specificity at 64.1% and 2.16 times higher positive predictive value (PPV) than HPV16/18 or LBC. <i>PAX1</i>^<i>m</i> and HPV16/18 + <i>PAX1</i>^<i>m</i> test achieved the area under the receiver operator characteristic (ROC) curves (AUC) for CIN3 + lesions with 0.837 and 0.792, respectively. The <i>PAX1</i>^<i>m</i> 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 <i>PAX1</i>^<i>m</i> test and 38.7% (95%CI: 36.3%–41.3%) with HPV16/18 + <i>PAX1</i>^<i>m</i> test compared to LBC at 82.1% (95%CI: 80.0%–83.9%). No cervical cancer cases were missed by <i>PAX1</i>^<i>m</i> test.</p> Conclusion <p>The <i>PAX1</i>^<i>m</i> 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.</p> Trial registration <p>Not available.</p>