Introduction/Background Endometrial cancer incidence is rising. Delays in diagnosis reduce survival and necessitate more aggressive treatment.

We developed the qPCR-based WID-qEC test that evaluates DNA methylation in GYPC and ZSCAN12 genes for detecting uterine cancer.

In a prospective, observational study, we compared the performance of conventional index imaging and the WID-qEC for endometrial cancer detection in symptomatic women.

Methodology We invited all women aged ≥ 45 years with abnormal uterine bleeding attending a tertiary gynaecological diagnostic referral centre in London between June and November 2022 to participate. A cervicovaginal sample for the WID-qEC test was obtained before the current diagnostic pathway and analyzed blinded to clinical outcome.

Results 399 women participated. Reference histology was recommended for 186 (46.6%) women. 198 reference histology test procedures detected nine cancers and missed two; one further cancer was directly diagnosed by hysterectomy. Endometrial thickness assessment using ultrasound was possible in 95.0% of women. A ≥4.5mm threshold showed sensitivity of 90.9% and specificity of 79.1%. The WID-qEC test was possible in 97.7% of women, with sensitivity of 90.9% and specificity of 92.1% using a prespecified threshold.

Additionally, we assessed different sample collection systems [FLOQSwab/eNAT medium (Copan) or Cervex brush/ThinPrep PreservCyt medium (Hologic)] in 16 women with high suspicion of endometrial cancer. WID-qEC results in Copan and Hologic samples were strongly correlated [0.89 (P<0.01)], and both systems detected endometrial cancer in 15/16 samples. The one sample with negative WID-qEC result in both systems was from a patient without a cancer diagnosis at the time of sampling.

Conclusion 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%. Using the Copan collection system, the WID-qEC test can easily be implemented into high-throughput diagnostic workflows.

Disclosures ER, IE, AJ and MW are named inventors on intellectual property filings that protects the commercialisation of the WID®-qEC test. CH and MW are shareholders of Sola Diagnostics GmbH, which holds an exclusive licence to the intellectual property that protects the commercialisation of the WID-qEC test. DJ is an unpaid advisory board member of the International Society for Ultrasound in Obstetrics and Gynecology. MW received funding from the Land Tirol, The Eve Appeal, and the European Research Council. All other authors declare no competing interests.