Abstract IA007: The WID-qEC test for simple and accurate endometrial cancer detection

Abstract

Abstract Endometrial cancer incidence has been rising over the past ten years. Delays in diagnosis reduce survival and necessitate more aggressive treatment. We developed the WID-qEC test, a PCR-based test that evaluates DNA methylation in gene regions of GYPC and ZSCAN12, using 726 cervico-vaginal samples from women with and without endometrial cancer. So far, the WID-qEC test has been validated in an additional 1388 women in various settings, including a case/control study utilizing self-samples and a nested case/control set from a screening cohort including samples taken up to 3 years prior to endometrial cancer diagnosis. In a recent prospective observational study (the EPI-SURE study), the primary aim was to compare the performance of conventional index imaging tests (i.e., sonography) with the WID-qEC test for endometrial cancer detection. We invited all women aged ≥ 45 years with abnormal uterine bleeding attending a tertiary gynecological diagnostic referral center in the UK between June and November 2022 to participate. A cervicovaginal sample for the WID-qEC test was obtained prior to the current diagnostic pathway, and the test was performed blinded to the clinical outcome. Patients were followed until diagnostic resolution or until June 12, 2023. Four hundred of the eligible 474 women consented to study participation; one patient withdrew. Based on 603 index imaging tests (i.e., sonography), 186 (46.6%) women were recommended for a reference histology test (i.e., biopsy+/-hysteroscopy). Twelve cancers were diagnosed. 198 reference histology test procedures detected nine cancers and missed two; one further cancer was directly diagnosed at hysterectomy without a prior reference test. Endometrial thickness assessment from an ultrasound scan was possible in 379 (95.0%) of the 399 women and a pre-specified cut-off of ≥ 4.5mm had sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of 90.9% (95% CI: 62.3-98.4), 79.1% (95% CI: 74.5-82.9), 11.8% (95% CI: 6.5-20.3) and 99.6% (95% CI: 98.0-99.9), respectively. Using a cut-off of > 3mm, the specificity was 45.8% (95% CI: 40.7–51.0) without a change in sensitivity. The WID-qEC test was possible in 390 (97.7%) of the 399 patients with 90.9% sensitivity (95% CI: 62.3-98.4), 92.1% specificity (95% CI: 88.9-94.4), a PPV of 25.6% (95% CI:14.6-41.1) and a NPV of 99.7% (95% CI: 98.3-99.9) when the pre-specified threshold (WID-qEC sumPMR ≥ 0.03) was applied. When a higher threshold was applied (WID-qEC sumPMR ≥ 0.3) the specificity increased to 97.3% (95% CI: 95.1-98.5) without a change in sensitivity. The WID-qEC test delivers fast results and shows improved performance compared with a combination of imaging index tests. Triage of women with abnormal uterine bleeding using the WID-qEC test could reduce the number of women requiring histological assessments for identification of potential malignancy and, specifically, reduce the false positive rate by up to 95% (from 52.6% based on the endometrial thickness of > 3mm to 2.6% based on a WID-qEC sumPMR ≥ 0.3). Citation Format: Martin Widschwendter, Iona Evans, Daniel Reisel, Allison Jones, Alba Bajrami, Simrit Nijjar, Sarah A Solangon, Rupali Arora, Elisa Redl, Lena Schreiberhuber, Isma Ishaq-Parveen, Julia Rothärmel, Chiara Herzog, Davor Jurkovic. The WID-qEC test for simple and accurate endometrial cancer detection [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA007.