Clinical performance of triage strategies for HPV-positive women in cervical cancer screening in rural Yunnan China.

OBJECTIVE: To evaluate the clinical performance of triage strategies for HPV-positive women in rural Yunnan, China, with the aim of optimizing HPV test-based cervical cancer screening. METHODS: We recruited 417 HPV-positive women, who additionally underwent mRNA testing, AI-assisted cytology, PAX1 and SOX1 DNA methylation testing. We compared the sensitivity, specificity, area under the curve (AUC), and number needed to colposcopy for one cervical lesion detection of several triage approaches, for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). RESULTS: Among single triage strategies, cytology demonstrated a sensitivity of 54.2% (95% CI: 33.2%-73.8%), a specificity of 75.1% (95% CI: 70.4%-79.2%), an AUC of 0.65 (95% CI: 0.53-0.77), and an number needed to colposcopy for one lesion detection of 8.5. Compared with cytology, PAX1 methylation exhibited superior sensitivity (87.5%, 95% CI: 66.5%-96.7%) and specificity (90.6%, 95% CI: 87.1%-93.2%), with an improved AUC of 0.89, and a reduced colposcopy referral of 2.8. Adding SOX1 to PAX1 maintained sensitivity (87.5%) but slightly reduced specificity (88.3%), resulting in an AUC of 0.88. mRNA testing showed higher sensitivity (75.0%) but lower specificity (44.5%) and a declined AUC (0.60). Among combined triage strategies, HPV-16/18 genotyping with reflex cytology for non-16/18 types yielded a sensitivity of 62.5%, a specificity of 54.5%, and an AUC of 0.59. HPV-16/18 genotyping with reflex PAX1/SOX1 methylation improved sensitivity to 91.7% and specificity to 64.1%, with an AUC of 0.78. CONCLUSION: PAX1 methylation triage demonstrated better clinical performance and required fewer colposcopy referrals than cytology triage. It showed good potential as an triage strategy for HPV-positive women in rural Yunnan. The addition of SOX1 methylation or integration with HPV genotyping did not significantly enhance its clinical performance.