Efectiveness analysis and clinical application potential exploration of combined detection of PAX1/JAM3 gene methylation in early diagnosis of cervical precancerous lesions

METHODS: This study included 431 cervical exfoliated cell samples, which consisted of CIN1, CIN2/3, cervical cancer (CC), and control groups. The methylation levels of the PAX1/JAM3 genes were assessed using quantitative methylation-specific PCR. The diagnostic efficacy of these genes for high-grade lesions (CIN2+) was analyzed through receiver operating characteristic (ROC) curve analysis and was compared with HPV testing and cytological examination. Additionally, the diagnostic performance of PAX1/SOX1 methylation was preliminarily evaluated in a sub-cohort of 100 cases. Further evaluation was conducted on the triage referral rate and the impact of clinical intervention using this biomarker in HPV-positive patients

RESULTS: The area under the curve (AUC) for the PAX1/JAM3 methylation test in diagnosing CIN2+ was 0.89 (95% CI: 0.85-0.92), with a sensitivity of 83.1% and a specificity of 88.8%. In the sub-cohort, the PAX1/SOX1 combination also demonstrated high diagnostic potential for CIN3+ (AUC = 0.91), serving as a validation of methylation testing efficacy. In non-HPV16/18 positive patients, the sensitivity and specificity of methylation testing for CIN2+ were superior to those of cytology. Among patients undergoing colposcopy, 265 cases had results of ��ASCUS, of which 51 were methylation positive, resulting in a colposcopy referral rate of 19.3%

CONCLUSION: PAX1/JAM3 gene methylation testing demonstrates strong diagnostic efficacy for cervical precancerous lesions and holds significant potential in triage diagnosis. The PAX1/SOX1 panel also shows promise as a complementary biomarker.