19 General introduction Lung cancer is currently diagnosed by conventional imaging and biopsy procedures. When a suspected nodule is observed during imaging, a biopsy is performed for further characterization by bronchoscopy, radiologically guided transthoracic needle biopsy, or a linear endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) (90). Procedures used for lung cancer diagnostics are expensive and susceptible to complications (91). Localization and size of the nodule are important determinants for the collection of sufficient lung tissue for diagnosis. In some cases, repeated sampling is required which may lead to delays in treatment initiation (92). Liquid biopsy has already entered lung cancer diagnostics to overcome tissue sampling issues. This FDA-approved plasma-based test for EGFR mutations showed high concordance with tissue (93) and highlights the promising potential of molecular testing in liquid biopsies when tissue availability is limited (94). 1.6 Thesis rationale and outline The overall objective of this thesis is to develop patient-friendly cancer detection methods to advance cancer diagnostics by focusing on DNA methylation analysis in urine for the detection of endometrial, ovarian, and lung cancer. For endometrial and ovarian cancer, also alternative patient-friendly sampling methods are assessed, including self-collected cervicovaginal samples and clinician-taken cervical scrapes (Figure 5). Cervicovaginal self-sample Clinician-taken cervical scrape Urine Label Figure 5: Patient-friendly sample types investigated in this thesis: urine, cervicovaginal selfsamples, and clinician-taken cervical scrapes. Created with BioRender.com. 1
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