Introduction/Background Minimally abnormal screening results are typically defined as cytological tests that include atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSILs). Due to the low prevalence of cervical precancerous lesions or cancers in women with minimally abnormal screening results, the management of such cases presents a significant challenge.

Methodology Cervical cytological samples from a cohort of over 7,000 women who underwent cervical cancer screening were subjected to high-risk human papillomavirus (hrHPV) DNA assays, cytological pathology and PAX1 and JAM3 dual-gene methylation (PAX1m/JAM3m) testing. The diagnostic accuracy of the methylation assay for cervical intraepithelial neoplasia of grade 3 or invasive cancers (CIN3+) was analysed in women with ASC-US or LSILs in cervical cytology.

Results In the detection of CIN3+ in women with ASC-US or LSIL, the sensitivity and specificity of hrHPV, PAX1m/JAM3m and hrHPV/PAX1m/JAM3m were found to be 93% and 40%, 55% and 91%, and 50% and 94%, respectively. The sensitivity of PAX1m/JAM3m was 100% in detecting invasive cancers. Utilizing an immediate risk threshold of ≥4.84 for CIN3+, the colposcopy referral rate was 33% for the screening strategy that combined cytology and hrHPV assay and 25% for the strategy that combined cytology, hrHPV assay and PAX1m/JAM3m testing. The screening strategy that incorporated the PAX1m/JAM3m test into cytology combined with hrHPV assay resulted in an 8% reduction in colposcopy referrals for the cohort and a 19% reduction for women under 35 years of age while maintaining CIN3+ referrals at 77.5% in both screening strategies.

Conclusion In women with minimally abnormal cytological findings, PAX1m/JAM3m testing significantly improved the specificity of CIN3+ identification and reduced the rate of unnecessary referrals, especially in younger women.

Disclosures Conflict of Interest Disclosure Statement

The European Society of Gynaecological Oncology requires clear disclosures from all presenters at its annual congress regarding any financial holdings, funding sources, or affiliations that might raise questions of bias or be perceived to have potentially influenced presentation content.

Please disclose any financial relationship from the past three years (dating from the month of submission) of any size.

NAME Lei Li

Department of Obstetrics and Gynecology,National Clinical Research Center for Obstetric & Gynecologic Diseases,State Key Laboratory for Complex, Severe and Rare Diseases, Peking Union Medical College Hospital

I have no potential conflict of interest to report

Signature Lei Li Date: November 9th