Lena Schreiberhuber

Performance of the WID‐qEC test to detect uterine cancers in black women with abnormal uterine bleeding: A prospective observational cohort study in Ghana

AbstractThe burden of uterine cancer is growing and, in the US and UK, mortality rates are poorest among black women. Early detection of these cancers is critical and poor performance of ultrasound in black women may contribute to adverse outcomes. Limited data on this topic are available from Africa. We assessed whether a simple DNA methylation test, the WID‐qEC, enables detection of all epithelial uterine (endometrial and cervical) cancers in women presenting with abnormal uterine bleeding (AUB) in Ghana. Among 118 women ≥40 years presenting with AUB, 106 consented to the study and a cervicovaginal sample was obtained for WID‐qEC testing. Subsequent to ultrasound assessment 102 women had a cervical or endometrial biopsy. Histopathology, ultrasound and WID‐qEC testing were analyzed and compared. Among the 102 volunteers, 8 and 15 were diagnosed with endometrial and cervical cancer (EC and CC), respectively. The receiver operating characteristic (ROC) area under the curve (AUC) was 0.56 (95% confidence interval [CI] 0.25–0.86) for sonographic endometrial thickness (ET) and 0.98 (95% CI 0.94–1.00) for the WID‐qEC test. Sensitivity and specificity of the prespecified ET ≥5 mm were 66.7% (95% CI 24.1–94.0) and 22.7 (95% CI 12.0–38.2) and for the prespecified WID‐qEC SUM‐PMR ≥ 0.3 were 100% (95% CI 56.1–100.0) and 76.1 (96%CI 60.9–86.9), respectively. In addition, 15 CCs were detected by the WID‐qEC test [sensitivity 100% (95% CI 74.7–100.0)]. The WID‐qEC test accurately detects both EC and CC in black women presenting with AUB.

High performance of the DNA methylation‐based WID‐qEC test for detecting uterine cancers independent of sampling modalities

AbstractEndometrial cancer (EC) is the most prevalent gynaecological cancer in high‐income countries and its incidence is continuing to rise sharply. Simple and objective tools to reliably detect women with EC are urgently needed. We recently developed and validated the DNA methylation (DNAme)‐based women's cancer risk identification—quantitative polymerase chain reaction test for endometrial cancer (WID‐qEC) test that could address this need. Here, we demonstrate that the stability of the WID‐qEC test remains consistent regardless of: (i) the cervicovaginal collection device and sample media used (Cervex brush and PreservCyt or FLOQSwab and eNAT), (ii) the collector of the specimen (gynaecologist‐ or patient‐based), and (iii) the precise sampling site (cervical, cervicovaginal and vaginal). Furthermore, we demonstrate sample stability in eNAT medium for 7 days at room temperature, greatly facilitating the implementation of the test into diagnostic laboratory workflows. When applying FLOQSwabs (Copan) in combination with the eNAT (Copan) sample collection media, the sensitivity and specificity of the WID‐qEC test to detect uterine (i.e., endometrial and cervical) cancers in gynaecologist‐taken samples was 92.9% (95% confidence interval [CI] = 75.0%–98.8%) and 98.6% (95% CI = 91.7%–99.9%), respectively, whilst the sensitivity and specificity in patient collected self‐samples was 75.0% (95% CI = 47.4%–91.7%) and 100.0% (95% CI = 93.9%–100.0%), respectively. Taken together these data confirm the robustness and clinical potential of the WID‐qEC test.

A Simple Cervicovaginal Epigenetic Test for Screening and Rapid Triage of Women With Suspected Endometrial Cancer: Validation in Several Cohort and Case/Control Sets

PURPOSE Endometrial cancer (EC) incidence has been rising over the past 10 years. Delays in diagnosis reduce survival and necessitate more aggressive treatment. We aimed to develop and validate a simple, noninvasive, and reliable triage test for EC to reduce the number of invasive diagnostic procedures and improve patient survival. METHODS We developed a test to screen and triage women with suspected EC using 726 cervical smear samples from women with and without EC, and validated the test in 562 cervicovaginal samples using three different collection methods (cervical smear: n = 248; vaginal swab: n = 63; and self-collection: n = 251) and four different settings (case/control: n = 388; cohort of women presenting with postmenopausal bleeding: n = 63; a cohort of high-risk women with Lynch syndrome: n = 25; and a nested case/control setting from a screening cohort and samples taken up to 3 years before EC diagnosis: n = 86). RESULTS We describe the Women's cancer risk IDentification – quantitative polymerase chain reaction test for Endometrial Cancer (WID-qEC), a three-marker test that evaluates DNA methylation in gene regions of GYPC and ZSCAN12. In cervical, self-collected, and vaginal swab samples derived from symptomatic patients, it detected EC with sensitivities of 97.2% (95% CI, 90.2 to 99.7), 90.1% (83.6 to 94.6), and 100% (63.1 to 100), respectively, and specificities of 75.8% (63.6 to 85.5), 86.7% (79.3 to 92.2), and 89.1% (77.8 to 95.9), respectively. The WID-qEC identified 90.9% (95% CI, 70.8 to 98.9) of EC cases in samples predating diagnosis up to 1 year. Test performance was similar across menopausal status, age, stage, grade, ethnicity, and histology. CONCLUSION The WID-qEC is a noninvasive reliable test for triage of women with symptoms suggestive of ECs. Because of the potential for self-collection, it could improve early diagnosis and reduce the reliance for in-person visits.

The WID‐qEC test: Performance in a hospital‐based cohort and feasibility to detect endometrial and cervical cancers

AbstractThe majority of endometrial and cervical cancers present with abnormal vaginal bleeding but only a small proportion of women suffering from vaginal bleeding actually have such a cancer. A simple, operator‐independent and accurate test to correctly identify women presenting with abnormal bleeding as a consequence of endometrial or cervical cancer is urgently required. We have recently developed and validated the WID‐qEC test, which assesses DNA methylation of ZSCAN12 and GYPC via real‐time PCR, to triage women with symptoms suggestive of endometrial cancer using ThinPrep‐based liquid cytology samples. Here, we investigated whether the WID‐qEC test can additionally identify women with cervical cancer. Moreover, we evaluate the test's applicability in a SurePath‐based hospital‐cohort by comparing its ability to detect endometrial and cervical cancer to cytology. In a set of 23 cervical cancer cases and 28 matched controls the receiver operating characteristic (ROC) area under the curve (AUC) is 0.99 (95% confidence interval [CI]: 0.97‐1.00) with a sensitivity and specificity of 100% and 92.9%, respectively. Amongst the hospital‐cohort (n = 330), the ROC AUC is 0.99 (95% CI: 0.98‐1) with a sensitivity and specificity of 100% and 82.5% for the WID‐qEC test, respectively, and 33.3% and 96.9% for cytology (considering PAP IV/V as positive). Our data suggest that the WID‐qEC test detects both endometrial and cervical cancer with high accuracy.

Evaluation of DNA Methylation Markers for Endometrial Cancer Risk-stratification Using Patient-collected Urine and Vaginal Samples and Clinician-collected Cervical Samples From Women With Postmenopausal Bleeding

The goal of this observational study is to investigate the clinical utility of DNA-methylation testing in urine and vaginal samples collected by patients and cervical samples collected by clinicians, to determine the risk of endometrial cancer in symptomatic women with postmenopausal bleeding. The study aims to answer the following research questions: * What is the diagnostic accuracy of DNA methylation testing in urine, vaginal and cervical samples compared to traditional TVUS for endometrial cancer detection? * What is the 2-year risk of EC among women testing negative on TVUS and/or DNA methylation tests or those testing positive on methylation only? Researchers will compare DNA methylation testing in patient-collected urine and vaginal samples as well as in clinician-collected cervical samples, with the traditional diagnostic pathway for women with PMB, which includes TVUS evaluation, and when indicated by abnormal TVUS findings, endometrial biopsy according to clinical guidelines. Participants will * take a urine and vaginal sample * have a cervical sample collected by a clinician * undergo TVUS evaluation according to clinical guidelines * If TVUS shows thickened endometrium (≥ 5 mm) and/or irregularity, an endometrial biopsy will be collected according to clinical guidelines * fill out a questionnaire regarding acceptability and preferences of sampling methods and complete a lifestyle questionnaire.

The Clinical Utility of DNA Methylation Testing in Patient-collected Urine and Vaginal Samples to Detect Endometrial Cancer: a Case-control Study

The goal of this observational case-control study is to investigate the use of DNA-methylation testing in patient-collected urine and vaginal samples to detect endometrial cancer. The study aims to answer the following questions: * Can DNA methylation testing in vaginal and full-void urine samples distinguish endometrial cancer cases from healthy controls? Researchers will compare patient-collected urine and vaginal samples from patients with diagnosed endometrial cancer (cases) to gynaecologically and oncologically healthy controls (controls). Participants will * take a urine and vaginal sample at the hospital. * answer a questionnaire regarding acceptability and preferences of self-sampling methods. * answer a lifestyle questionnaire.

Clinical Studies of Endometrial Cytology and Cervical Methylation Assays in Endometrial Cancer Screening and Fertility-Preservation Evaluation

The current study aims to assess high-risk patients using both liquid-based cytology and cervical methylation testing. The results will be compared with the traditional hysteroscopic pathological findings to determine the sensitivity and specificity of these methods for early detection of endometrial cancer, thereby evaluating their potential application in early screening. Primary Objectives： 1. To evaluate the sensitivity, specificity, and accuracy of endometrial cytology for screening endometrial cancer. 2. To assess the sensitivity, specificity, and accuracy of methylation testing for screening endometrial cancer. 3. To perform further molecular testing on tissue samples obtained from endometrial cytology and cervical methylation tests, aiming to explore early screening-sensitive indicators. Secondary Objectives： 1. To determine the value of endometrial cytology in evaluating the efficacy of fertility-sparing treatments for endometrial cancer. 2. To assess the value of methylation testing in evaluating the efficacy of fertility-sparing treatments for endometrial cancer.