In a UK single-institution study (EPI-SURE) reported in The Lancet Oncology, Evans et al found that the novel WID-qEC DNA methylation test outperformed ultrasonography in detecting uterine cancer in women with abnormal uterine bleeding.
Study Details
The prospective observational study invited participation of all women aged ≥ 45 years with abnormal uterine bleeding attending a gynecologic diagnostic referral center at University College London Hospital between June 2022 and November 2022. Cervicovaginal samples for WID-qEC testing were obtained prior to assessment with index imaging tests (ie, ultrasound) and, when performed, reference histology (ie, biopsy or hysteroscopy or both). The result of the WID-qEC test is defined as the sum of the percentage of fully methylated reference (ΣPMR) of the ZSCAN12 and GYPC regions.
Key Findings
A total of 399 of 474 eligible women participated in the study. On the basis of 603 index imaging tests, 186 (47%) were recommended for a reference histology test. A total of 12 women were diagnosed with cancer, 375 were not diagnosed with cancer, and 12 had inconclusive clinical outcomes and were considered study dropouts. A total of 198 reference histology tests detected nine cases of cancer and missed two; one case of cancer was directly diagnosed at hysterectomy without a reference test.
The receiver operating characteristic area under the curve values for detection of uterine cancer was 87.2% (95% confidence interval [CI] = 71.1%–100%) based on endometrial thickness in mm vs 94.3% (95% CI = 84.7%–100%) based on WID-qEC (P = .48).
Endometrial thickness measurement on ultrasound scan was performed in 379 women (95%). A prespecified cutoff of ≥ 4.5 mm was associated with a sensitivity of 90.9% (95% CI = 62.3%–98.4%), a specificity of 79.1% (95% CI = 74.5%–82.9%), a positive predictive value of 11.8% (95% CI = 6.5%–20.3%), and a negative predictive value of 99.6% (95% CI = 98.0%–99.9%) for detection of cancer.
The WID-qEC test was performed in 390 women (98%). A prespecified threshold of ≥ 0.03 ΣPMR was associated with a sensitivity of 90.9% (95% CI = 62.3%–98.4%), a specificity of 92.1% (95% CI = 88.9%–94.4%), a positive predictive value of 25.6% (95% CI = 14.6%–41.1%), and a negative predictive value of 99.7% (95% CI = 98.3%–99.9%).
The investigators concluded: “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.”
Martin Widschwendter, MD, of the Department of Women’s Cancer, EGA Institute for Women’s Health, University College London, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by The Eve Appeal, Land Tirol, and European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme. For full disclosures of the study authors, visit thelancet.com.
