Identification of miRNAs and other ncRNAs as biomarkers for cervical cancer and assessment of their potential functional relevance in HPV-mediated transformation
01 / 2010 - 12 / 2014
An infection with high-risk HPV is necessary, but not sufficient for malignant transformation of epithelial cells. In vitro studies have demonstrated that progression of an hrHPV-infected cell to an immortal and subsequent invasive phenotype results from the accumulation of specific (epi)genetic alterations in the host cell genome. This research line aims at identifying the host cell alterations functionally involved in HPV-mediated transformation, and subsequently evaluating their potential value as biomarker to stratify HPV-positive women for risk of (pre)malignant disease. Towards this aim, functional studies using in vitro model systems of HPVtransformedhuman keratinocytes are complemented with studies on clinically annotated specimens of women with and without cervical disease using both genome-wide and candidate gene approaches. Cervical cancer development is initiated by a hrHPV infection. In the course of various projects the impact of this finding is evaluated at the level of prevention, diagnostics, test of cure, and prophylactic vaccination (see also www.humavac.nl). At the moment, the main focus is on the development of primary screening algorithms for both cervical scrapings and self-collected (cervico-)vaginal samples, using HPV testing followed by triage of HPV-positive women by cytology, viral parameters, and/or molecular disease markers. Human papillomavirus (HPV) infections have not only shown to be associated with cervical cancer, but with non-cervical anogenital cancers, and HNSCC as well. However, to what extend HPV infections are involved in carcinogenesis of these types of cancers in the Netherlands is not completely known yet.