Acceptability and somatic mutations in cervicovaginal self-sampling for early endometrial cancer detection in women with Lynch syndrome

Abstract

New molecular approaches are being developed to detect endometrial cancer using minimally invasive sampling methods. This study aims to evaluate the acceptability of self-collected cervicovaginal samples among women with Lynch syndrome, a group at high risk for developing endometrial cancer. Participants collected cervicovaginal self-samples and answered an at-home acceptability questionnaire in a cross-sectional study. Self-samples from a subset of these women were analyzed for somatic mutations using next-generation sequencing (NGS), targeting a panel of 47 genes. A total of 61 (88.4%) out of 69 eligible women participated in the study. The overall self-sampling experience was rated good or very good (N = 55, 90.2%). Most of the women were confident about correctly sampling (N = 58, 95.1%), and most reported no or mild pain (N = 56, 91.8%). During self-sample collection, most women reported feeling calm and comfortable and experiencing safety, privacy, and normality. In a pilot study using a subset of 15 samples, five somatic variants were identified in four self-samples (4/15, 26.7%) in ACVR2A, ARID1A, APC, and KMT2D. During follow-up, three out of four women with variants detected in the self-sample underwent prophylactic hysterectomy at a median of 9.1 months, while one out of four developed endometrial cancer after 3.9 years since the collection of the sample. Self-sampling is well-accepted and well-tolerated in women with Lynch syndrome and could potentially reduce some barriers associated with gynaecological surveillance. Further research is needed to evaluate the feasibility of implementing cervicovaginal self-collection and the accuracy of molecular testing for gynaecological surveillance in women with Lynch syndrome.