Introduction/Background Biopsies, with or without hysteroscopy, are common procedures for evaluating endometrial lesions but carry significant risks, including bleeding and infection, causing patient distress. The need for a non-invasive and reliable triage strategy for potential endometrial malignant lesions is evident. Such a strategy can reduce unnecessary invasive diagnostic procedures, enhancing the overall patient experience during the diagnostic process. Herein, we assess the diagnostic potential of DNA methylation levels in cervical cytological samples for endometrial cancer (EC) and endometrial atypical hyperplasia (AH).

Methodology A total of 607 women indicated for endometrial biopsy were enrolled at the Department of Obstetrics and Gynaecology of Cangzhou Central Hospital from October 2022 to April 2023. Cervical exfoliated cells were collected for DNA methylation before endometrial biopsy. Clinical information, tumor biomarkers, and endometrial thickness (ET) measured via transvaginal ultrasonography (TVUS) were also recorded. Multivariate unconditional logistic regression was applied to identify risk factors for endometrial malignant lesions using endometrial histopathology as the gold standard. The potential of CDO1 and CELF4 gene methylation (CDO1m/CELF4m) as biomarkers in triage strategies for patients with endometrial malignant lesions was specifically explored.

Results bnormal ET and CDO1m/CELF4m were identified as risk factors for AH and EC, with odds ratio of 5.03 and 6.92, respectively (P<0.05). CDO1m/CELF4m demonstrated a sensitivity and specificity of 85% and 87% for endometrial malignant lesions. When ET combined with CDO1m/CELF4m, specificity was further improved to 95%. In postmenopausal women, the sensitivity and specificity of CDO1m/CELF4m reached 94% and 80%, respectively, and the combination of ET and CDO1m/CELF4m further improved the specificity to 97%.

Conclusion The accuracy of DNA methylation analysis in cervical cytological samples surpasses that of other clinical indicators in the non-invasive examination of endometrial malignant lesions. CDO1m/CELF4m, when combined with TVUS, presents an attractive promising biomarker-based triage strategy for women with suspected endometrial lesions.

Disclosures 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: Bingli Qi

AFFILIATION: Department of Gynecologic Oncology and Surgery, Cangzhou Central Hospital

I have no potential conflict of interest to report

Signature: Bingli Qi Date: November 9th