First-void urine as a biomarker source for primary and secondary cervical cancer prevention

Within this thesis we aimed to investigate the opportunities of first-void urine as a liquid biopsy, harbouring biomarkers for cervical cancer prevention. First-void urine is a particularly interesting self-sample, as it non-invasively captures mucus and debris from exfoliated cells originating from the female genital organs, including the cervix. These cervicovaginal secretions accumulate around the urethra opening and small labia, and hence are washed away with the initial urine stream (first-void). As the value of using first-void urine for detection of Human Papillomavirus (HPV) DNA – the aetiological agent for cervical cancer – has been demonstrated, we hypothesised that also biomarkers could be present for (i) monitoring primary prevention (through vaccine-induced antibodies against HPV) and (ii) secondary cervical cancer prevention (specific biomarkers for cervical cancer screening and triage of high-grade precancerous lesions). First evidence was presented that HPV vaccine-induced antibodies are detectable in first-void urine, and able to discriminate vaccinees from unvaccinated women (chapter 2). Based on a review of the literature (chapter 3), interesting candidate biomarkers for screening were identified, followed by detection thereof in first-void urine samples. Good and excellent HR-HPV DNA and HPV16/18 DNA agreements between paired first-void urine and cervical samples were observed, as well as significant positive correlations in HPV copies on genotype level (chapter 4/A). Moreover, first-void urine sampling is well accepted among screening-eligible women. Detection of HPV E6/E7 mRNA is also feasible, yet, requires optimizations to improve sensitivity (chapter 4/B). Furthermore, we have demonstrated elevated host cell methylation marker levels in first-void urine with increasing severity of underlying disease (chapter 5). At last, a protocol was designed to test the accuracy of different HPV test/self-sampling combinations (chapter 6), allowing us to validate both HR-HPV primary screening and molecular triage compared to clinician- and self-collected cervical/cervicovaginal samples in the near future. In summary, this dissertation provided information and data, contributing to a better understanding of first-void urine as a resourceful liquid biopsy, containing biomarkers for primary as well as secondary cervical cancer prevention.

ISBN:978-90-5728-620-9

Publication year:2019

Keywords:Doctoral thesis

Accessibility:Open