Prospective Evaluation of Cervical Scrapings CDO1 and CELF4 Methylation (epiHERA®) Assay in Detection of Endometrial Cancer.

Background/Objectives: Our study evaluates the performance of the CDO1 and CELF4 methylation assay of cervical scrapings in diagnosing endometrial cancer. Methods: Patients referred for abnormal uterine bleeding, suspected endometrial pathology on imaging, endometrial hyperplasia, or cancer, who were indicated for endometrial sampling +/- hysteroscopy +/- hysterectomy, were recruited prospectively from the gynecology clinic of Prince of Wales Hospital, Hong Kong, from January 2023 to November 2024. Methylation assay was performed on the cervical scrapings of the participants, with the results compared to endometrium histology obtained on the same day. Results: Methylation assay results of 675 patients were compared to 629 outpatient endometrial assessments and 46 hysterectomy histology. The assay yields an accuracy of 97.3%, sensitivity of 84.1%, specificity of 98.8%, PPV of 89.2%, and NPV of 98.2%. The AUC is 0.92 with a Kappa coefficient of 0.85. The false-negative rate was 0.8% among the 629 endometrial assessment cases. Endometrial thickness, abnormal cervical cytology, and endometrial hyperplasia significantly affected the accuracy. Among seven false-positive cases, five had endometrial hyperplasia and two had cervical intraepithelial neoplasia. Eventually, three patients were diagnosed with endometrial cancer and one with cervical cancer 1 to 4 months later. Conclusions: Methylation assay of cervical scrapings is highly accurate in diagnosing endometrial cancer with a high sensitivity, specificity, and low false-negative rate. It can act as a triage to reduce invasive endometrial assessment. All false-positive cases were related to neoplastic processes in the genital tract, indicating that it may be useful for detecting cancer early, before histological change is evident.