Enhanced diagnostic accuracy of high‐grade cervical intraepithelial neoplasia in postmenopausal women through <scp> <i>PAX1</i> </scp> / <scp> <i>JAM3</i> </scp> methylation analysis

This study aimed to assess the diagnostic-support and triage value of PAX1/JAM3 methylation testing for identifying high-grade cervical lesions among postmenopausal women referred for colposcopy. A total of 216 women aged ≥50 years who underwent colposcopy due to positive high-risk human papillomavirus (hrHPV)/cytology detection and/or abnormal clinical symptoms were included, and 212 women aged <50 years matched 1:1 by hrHPV and cytology results as the control group. The effectiveness of PAX1/JAM3 methylation in detecting high-grade cervical intraepithelial neoplasia (CIN) was compared to traditional screening methods. PAX1/JAM3 methylation showed a sensitivity of 93.2%[85.7%-100%] for detecting CIN2+ lesions (97.2%[91.9%-100%] for CIN3+), with a specificity of 93.6%[89.9%-97.3%] for CIN1-lesions, outperforming liquid-based cytology (LBC) (CIN2+/CIN3+ sensitivity: 75%[60.9%-89.1%]; specificity: 52.3%[44.9%-59.8%]) and the combination of LBC and hrHPV tests according to current guidelines (CIN2+/CIN3+ sensitivity: 81.8%[70.4%-93.2%]/83.3%[71.2%-95.5%]; specificity: 45.3%[37.9%-52.8%]). Methylation detection successfully identified two adenocarcinoma cases with negative hrHPV and LBC, as well as 7 patients with non-16/18 hrHPV infection that were missed by LBC. The methylation levels of PAX1 and JAM3 were elevated in elderly women with CIN2+ compared to younger women, and showed no association with HPV types. In conclusion, PAX1/JAM3 methylation testing showed promising diagnostic-support performance among postmenopausal women referred for colposcopy, suggesting potential utility as a supplementary detection method to improve diagnostic accuracy in older women.