Annals of medicine · 2026
Differential diagnostic value of PAX1 and JAM3 methylation for cervical intraepithelial neoplasia between premenopausal and postmenopausal women: a retrospective clinical study in China.
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Wang Peixin, Zhang Mengyu, Lai Yucheng, Song Tao, Shen Yan, Chen Haiying, Chen Xiaoyan
Аннотация
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.