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

Abstract

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.