The value of paired box gene 1 methylation detection in the triage of high-grade cervical lesions in high-risk human papillomavirus-positive populations

Objective: This study aimed to investigate the role of paired box gene 1 (PAX1) methylation in exfoliated cervical cells for triaging high-risk human papillomavirus (HR-HPV)-positive patients. Methods: Patients with positive HR-HPV DNA test results who underwent pathological biopsy at the First Affiliated Hospital of USTC were enrolled. Existing results of the ThinPrep cytologic test (TCT) and DNA ploidy analysis were also collected. The diagnostic efficacy and triage performance of PAX1 methylation testing in HR-HPV-positive patients were evaluated and compared. Results: Among the 177 HR-HPV-positive patients, 72 had a negative histological diagnosis, 63 had low-grade squamous intraepithelial lesions (LSILs), 40 had high-grade squamous intraepithelial lesions (HSILs), and 2 had cervical cancer. The PAX1 methylation positivity rates in these groups were 2.8% (2/72), 28.6% (18/63), 65% (26/40), and 100.0% (2/2), respectively. Spearman correlation analysis revealed a significant positive correlation between the PAX1 methylation rate and pathological grade (r = 0.560, P < 0.001). In HR-HPV-positive patients, PAX1 methylation testing demonstrated a sensitivity of 66.7%, a specificity of 85.2%, a positive predictive value (PPV) of 58.3%, a negative predictive value (NPV) of 89.2%, an accuracy of 80.8%, and an area under the receiver operating characteristic (ROC) curve (AUC) of 0.759. Compared with TCT (47.9%, 28.9%, 55.7%, and 0.681 for specificity, PPV, accuracy, and AUC, respectively) and DNA ploidy analysis (44.7%, 36.6%, 56.2%, and 0.665 for specificity, PPV, accuracy, and AUC, respectively), PAX1 methylation testing showed similar sensitivity and NPV but significantly higher specificity, PPV, accuracy, and AUC. Furthermore, the agreement between PAX1 methylation testing and pathological results (Kappa = 0.494) was greater than that between TCT (Kappa = 0.203) and DNA ploidy analysis (Kappa = 0.227). Conclusion: In HR-HPV-positive patients, the PAX1 methylation rate is positively correlated with pathological severity. Compared with TCT and DNA ploidy analysis, PAX1 methylation detection demonstrated superior specificity, PPV, accuracy, and diagnostic consistency for the diagnostic performance of HSIL+. It is more suitable as a secondary triage tool and can effectively reduce unnecessary diagnoses and treatments.