206 Chapter 8 SUMMARY High cancer mortality rates and the rising cancer burden worldwide prioritize the development of innovative methods that facilitate the early and accurate detection of cancer. Combining patient-friendly sampling methods with reliable biomarker testing offers a method that is convenient for patients and effective in detecting cancer at a curable stage, with improved patient outcomes as an ultimate goal. This thesis assessed the feasibility of DNA methylation testing in urine as a diagnostic tool for different cancer types, including endometrial, ovarian, and lung cancer. For endometrial and ovarian cancer, the value of DNA methylation testing in self-collected cervicovaginal samples and clinician-taken cervical scrapes was also investigated. Part 1: Endometrial and ovarian cancer detection in patient-friendly samples Part 1 describes the detection of endometrial and ovarian cancer in urine, cervicovaginal self-samples, and clinician-taken cervical scrapes. In Chapter 2, the feasibility of endometrial cancer detection in urine was evaluated. Three methylation markers (GHSR, SST, ZIC1), previously described for the accurate detection of cervical (pre)cancer, were measured in urine samples of endometrial cancer patients (n=42) and healthy controls (n=46). A comprehensive comparison of full void urine, urine sediment, and urine supernatant revealed that full void urine is most optimal for endometrial cancer detection. Full void urine allowed endometrial cancer detection with excellent discriminatory power with an area under the receiver operating curve (AUC) value of up to 0.95 for GHSR. This study was the first to demonstrate the feasibility of endometrial cancer detection in urine by DNA methylation analysis. Given these novel findings, in Chapter 3, a systematic review of the literature was performed to 1) summarize previous work on endometrial cancer detection in minimally invasive sample types and 2) select which methylation markers deserve further development. A systematic search starting with 1556 relevant papers, resulted in nine eligible studies describing methylation markers for endometrial cancer detection in minimally invasive sample types, including cervical scrapes, endometrial brushes, vaginal swabs, and vaginal tampons. A total of 15 markers with a high accuracy (AUC range 0.80-0.96) were considered most interesting for further studies. We also remarked that combining methylation markers in a panel may increase test sensitivity without any impact on test specificity. In Chapter 4, nine methylation markers were tested for endometrial cancer detection in paired urine, cervicovaginal self-samples, and clinician-taken cervical scrapes to
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