Abstract
PAX1/JAM3 methylation are promising biomarkers for high-grade cervical intraepithelial neoplasia (CIN) detection, but menopausal status may affect diagnostic accuracy. This retrospective study compared their clinical performance between premenopausal and postmenopausal women undergoing colposcopy. 705 women undergoing colposcopy for abnormal screening results and/or clinical symptoms were stratified by menopausal status, including 192 postmenopausal and 513 premenopausal women. Subjects were further classified into ≤CIN1 and CIN2+ groups according to histopathology. Diagnostic and triage utility of PAX1/JAM3 methylation for identifying CIN2+ lesions were compared between premenopausal and postmenopausal women. PAX1/JAM3 methylation demonstrated superior diagnostic performance for CIN2+ detection in postmenopausal women compared with premenopausal women, either alone or in combination. Sensitivities of PAX1m and JAM3m in postmenopausal women (90.00%, 95% CI: 76.34-97.21%; 82.50%, 95% CI: 67.22-92.66%) were higher than those in premenopausal women (61.98%, 95% CI: 52.71-70.65%; 60.33%, 95% CI: 51.04-69.11%) (all p < 0.05). The combination improved sensitivity to 72.73% in premenopausal women and maintained 92.50% in postmenopausal women. Besides, PAX1/JAM3 methylation outperformed cytology and HPV16/18 testing in both groups (p < 0.001). In HPV16/18-positive or cytology triage, methylation increased positive predictive values (PPVs) for CIN2+/CIN3+ and reduced colposcopy referrals . However, CIN2+ missed rates in premenopausal women (27.54% for HPV16/18-positive triage and 23.85% for cytology triage) were higher than those in postmenopausal counterparts. The diagnostic performance of PAX1/JAM3 methylation for high-grade cervical lesions differs distinctly between premenopausal and postmenopausal women undergoing colposcopy. Menopausal status should be considered when applying methylation biomarkers, particularly as a valuable auxiliary tool to improve diagnostic accuracy in elderly women.