Introduction/Background Currently, cervical cytology and HPV DNA testing are the most widely employed methods. However, these screening approaches possess inherent advantages and limitations that contribute to overdiagnosis or overuse of colposcopy, as over 30% of cases with CIN2, CIN3, and invasive cancers remain indistinguishable through cytology alone.

Methodology A total of 549 participants were enrolled in the study. Cervical brush sampling was performed on all participants to collect cervical exfoliated cells. These cells were then subjected to analysis using liquid-based cytology, HPV testing, and PAX1-JAM3 gene methylation detection (CISPOLY, China). The results obtained were compared with pathological findings.

Results A total of 549 participants were included in this study, encompassing various histological diagnoses across different age groups, including benign abnormalities (n=31), benign/CIN1 (n=321), CIN2 (n=44), CIN3 (n=36), cervical cancer (n=26), postoperative cases (n=28), and other malignant tumors (n=20). When compared to HPV testing (sensitivity: 94.68%, specificity: 9.95%) and liquid-based cytology (LBC) (sensitivity: 89.62%, specificity: 45.5%), dual-gene methylation detection of PAX1-JAM3 exhibited higher sensitivity (92.45%) and specificity (95.16%) for detecting CIN2 across all age groups. For CIN3, the methylation performance demonstrated a sensitivity of 98.39% and a specificity of 86.78%. In the population aged 50 years or older, dual-gene methylation detection exhibited a sensitivity of 100% and a specificity of 93.98% for detecting CIN2, surpassing the lower sensitivity (89.47%) and specificity (14.61%) of HPV testing and LBC (sensitivity: 91.3%, specificity: 54.17%). The misdiagnosis rates for cancer were 0% for PAX1-JAM3 dual-gene methylation detection, 5% for HPV testing, and 7% for LBC among all participants.

Conclusion Our findings demonstrate that gene methylation detection, when compared to HPV testing and cytology, shows promise in cervical cancer screening, particularly for patients with CIN2 or lower. It has the potential to serve as an independent biomarker for accurate cervical cancer diagnosis and triage among the Chinese population.