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

BACKGROUND: The early and accurate diagnosis of cervical precancerous lesions is essential for mitigating the risk of cervical cancer. Given the limitations of traditional screening methods, such as inadequate sensitivity and low specificity, this study aims to assess the diagnostic performance of combined PAX1/JAM3 gene methylation testing for cervical intraepithelial neoplasia (CIN) and to explore its potential in triage management. Methylation testing serves as a tool for investigating the epigenetic alterations associated with diseases like cancer, thereby providing molecular biological evidence for diagnosis and prognosis.

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.