The triage of Atypical Squamous Cells (ASC) is pivotal in cervical cancer (CC) screening. This study aimed to evaluate the performance of paired box 1 gene methylation (PAX1m) testing for triaging cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) in an ASC population and to compare it with high-risk human papillomavirus (hrHPV) testing. This retrospective study was conducted from June 2023 to October 2025 and analyzed 1,305 women with ASC. Residual cervical cell samples were used for PAX1m testing, and their hrHPV test results within two months were collected for comparison. All participants underwent colposcopy-biopsy to obtain the histopathological results. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity of the two methods was calculated and compared. difference of cross points (ΔCp) values showed a negative correlation with lesion severity (P trend <0.001). For CIN3 + detection, PAX1m (cut-off: ΔCp ≤ 11.74) demonstrated comparable sensitivity to hrHPV (94.6% vs. 94.6%), but with significantly higher specificity (66.0% vs. 10.4%, P < 0.001). Its AUC was also significantly higher to that of the hrHPV test. For CIN2 + detection, the AUC of PAX1m (cut-off: ΔCp ≤ 11.74) was 0.716, which was significantly higher than that of the hrHPV test (0.544, P < 0.001). Furthermore, PAX1m detected all cases of CC. In the triage of ASC, PAX1m significantly improved the specificity for detecting CIN3 + while maintaining high sensitivity. These findings suggest that PAX1m is a promising triage strategy with diagnostic performance superior to that of hrHPV, warranting further prospective validation of its clinical impact and cost-effectiveness.
Tao et al. (Fri,) studied this question.