PAX1/SOX1 gene methylation as a detection and triage method for triage of high risk HPV-Positive women in cervical cancer screening.

OBJECTIVE

To evaluate the role of PAX1/SOX1 methylation testing in the triage of HPV-positive patients and compare its performance with traditional screening methods, including HPV genotyping and cytology.

METHODS

A study was conducted from February 2024 to October 2024, involving women referred for colposcopy during the "two-cancer screening" in a specific region. Patients were grouped based on histopathological results [normal/cervicitis, cervical intraepithelial neoplasia 1 (CIN1), high-grade squamous intraepithelial lesion (HSIL), cervical cancer] and high-risk human papillomavirus (hrHPV) typing (HPV16/18 positive, other 12 hrHPV positive). Cervical exfoliated cell specimens were collected for PAX1/SOX1 methylation and liquid-based cytology testing. Methylation status was detected using a specific PCR-fluorescence probe kit, and cytology results were interpreted according to the 2022 Bethesda System (TBS) system.

RESULTS

The study included 640 participants. The mean Ct values of PAX1 and SOX1 decreased with the progression of cervical lesions. In the detection of high grad CIN+ (HG-CIN + ) in HPV-positive women, PAX1/SOX1 methylation testing showed higher AUCs (PAX1: 0.84; SOX1: 0.83) compared to HPV genotyping and cytology. For non-16/18 hrHPV positive cases, methylation testing had a better balance of sensitivity and specificity in detecting ≥ CIN2 and ≥ CIN3 lesions. Methylation testing also had the potential to reduce unnecessary colposcopy referrals in HPV-positive patients with cytology.

CONCLUSIONS

PAX1/SOX1 methylation testing shows potential as an effective adjunct to traditional cervical cancer screening methods. It can better identify high-grade lesions in HPV-positive patients and may reduce unnecessary referrals. However, larger-scale studies and long-term follow-up are needed to confirm its efficacy and optimize its integration into routine screening protocols.