93 DNA methylation testing for endometrial cancer detection in patient-friendly sample types (39, 40). Although their performance is excellent, they are probably not specific for endometrial cancer only and combining them with endometrial cancer-specific markers might be valuable for endometrial cancer-specific test development. Methylation of BHLHE22 and CDO1 in non-endometrioid cancers has previously been reported by Huang et al. (17) and Liew et al. (24) who identified and validated the performance of these genes in cervical scrapes. This panel is now commercially available as the MPapⓇ Test (37). Differences in methylation signatures between endometrioid and non-endometrioid tumors should be taken into account during the development of a methylation-based test to allow the detection of all (molecular) subtypes of endometrial cancer. DNA methylation analysis for endometrial cancer detection offers a sensitive molecular test, applicable to both minimally- and non-invasive sample types. This easy-to-apply approach offers the potential to reduce the number of biopsy procedures, thereby reducing costs and easing pressure on the healthcare system. The cervicovaginal self-sampling device provides a home-based sampling method which is introduced in the Dutch cervical cancer screening program to increase screening participation (41). Logistics around transport and sample processing of this sample type is already in place in diagnostic laboratories in The Netherlands, which eases its implementation for endometrial cancer diagnostics. Urine is another attractive diagnostic sample type for the detection of endometrial cancer (25). This liquid biopsy has gained more interest because it is easy to obtain and preferred by women over other sample types (42). Apart from locally shedded cellular tumor-DNA, urine also contains transrenally excreted tumor-derived cell-free DNA which poses an additional advantage (14, 43, 44). DNA methylation testing on patient-friendly sample types may contribute to the timely detection of endometrial cancer in patients with symptoms of postmenopausal bleeding. Moreover, this method is promising to screen asymptomatic women at risk for endometrial cancer (i.e. women with inherited cancer syndromes, such as Lynch or Cowden) which are currently intensively screened using repeated endometrial biopsies. This approach may reduce the number of invasive procedures within these patient groups and prioritize the use of resources for patients in greater need in times of scarcity. Methylation testing in patient-friendly samples could also be valuable for recurrence detection after curative intent treatment, as recently explored in plasma by Beinse et al. (45). To assess the clinical applicability of this approach for abovementioned purposes, DNA methylation testing needs to be further validated on samples of patients presenting with postmenopausal bleeding with varying final diagnoses (i.e. including women without 4
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