An Integrated Approach for the Early Detection of Endometrial and Ovarian Cancers (Screenwide Study): Rationale, Study Design and Pilot Study

Abstract

Screenwide is a case-control study (2017–2021) including women with incident endometrial and ovarian cancers (EC and OC), BRCA1/2 and MMR pathogenic variant carriers, and age-matched controls from three centers in Spain. Participants completed a personal interview on their sociodemographic factors, occupational exposure, medication, lifestyle, and medical history. We collected biological specimens, including blood samples, self-collected vaginal specimens, cervical pap-brush samples, uterine specimens, and, when available, tumor samples. The planned analyses included evaluation of the potential risk factors for EC/OC; evaluation of molecular biomarkers in minimally invasive samples; evaluation of the cost-effectiveness of molecular tests; and the generation of predictive scores to integrate different epidemiologic, clinical, and molecular factors. Overall, 182 EC, 69 OC, 98 BRCA pathogenic variant carriers, 104 MMR pathogenic variant carriers, and 385 controls were enrolled. The overall participation rate was 85.7%. The pilot study using 61 samples from nine EC cases and four controls showed that genetic variants at the variant allele fraction > 5% found in tumors (n = 61 variants across the nine tumors) were detected in paired endometrial aspirates, clinician-collected cervical samples, and vaginal self-samples with detection rates of 90% (55/61), 79% (48/61), and 72% (44/61) by duplex sequencing, respectively. Among the controls, only one somatic mutation was detected in a cervical sample. We enrolled more than 800 women to evaluate new early detection strategies. The preliminary data suggest that our methodological approach could be useful for the early detection of gynecological cancers.

Molecular analysis for ovarian cancer detection in patient-friendly samples

“…36 Their signature consisted of epigenetic differences in cervical cells and allowed ovarian cancer detection in cervical scrapes with an area under the receiver operating characteristic curve value of 0.76. Larger cohort studies, such as the Screenwide study 37 , will provide further insight into the use of cervicovaginal self-samples for ovarian cancer detection.…”

Total Effective Xenoestrogen Burden in Serum Samples and Risk of Endometrial Cancer in the Spanish Screenwide Case–Control Study

“…The study followed all the requirements established by the Ethics Committee for Clinical Research and was approved by the Ethics Committee for Clinical Research from the Bellvitge University Hospital (references: PR128/16 and PR348/19), as previously described in Peremiquel-Trillas et al. 38 Participation in the study was voluntary, and all eligible participants signed an informed consent form. The Screenwide study followed the national and international directives on ethics and data protection (Declaration of Helsinki and subsequent amendments; EU Reglament 2016/679) and the Spanish laws on data protection (Organic Law 3/2018; Law 14/2007 Biomedical Research).…”

Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancer

“…Consecutive incident endometrial cancer cases and controls frequency-matched by age in ±5 years groups were also enrolled. 15 Fig. 1 shows a graphical summary of the study.…”

“… 10 , 11 Recently, we and other researchers have assessed molecular markers in cervicovaginal samples for endometrial cancer detection in order to overcome these limitations. 12 , 13 , 14 , 15 Routine clinician-collected cervical samples and self-collected vaginal specimens are used in cervical cancer screening programs in order to detect human papillomavirus (HPV). 16 Although HPV has not been linked to the aetiology of endometrial cancer, 17 , 18 there is potential for these clinician- and self-collected cervicovaginal specimens to detect markers of cancers other than cervical cancer.…”

“…Molecular-based methods in these samples have shown great accuracy for detecting endometrial cancer, but most previous studies were affected by small sample sizes, lack of validation, and/or unmatched controls. 13 , 15 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 To date, none of these studies have demonstrated prognostic potential or the capacity to predict the molecular subtype of endometrial cancer. In this study, we evaluated a next-generation sequencing (NGS) approach in 339 cervicovaginal samples to detect endometrial cancer and developed a surrogate for the early molecular classification of this cancer.…”