Cervical cancer

Human papillomavirus (HPV) infection and cancer
Infection with high-risk HPV (hrHPV) has been recognized as the key causative event for cervical cancer, and has been found associated with some non-cervical anogenital cancers and head-and-neck squamous cell carcinoma as well. Our research involves aspects focusing on:

(I) Epidemiology, prevention and screening
Cervical cancer development is initiated by an 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 using HPV testing followed by triage of HPV-positive women by cytology, viral parameters, and/or molecular disease markers.

(II) Cervical carcinogenesis: unravelling of the multistep pathways using well-defined clinical material and in vitro cell culture model systems
An hrHPV infection 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 involved in HPV-mediated transformation, and evaluating their potential value as biomarker to stratify HPV-positive women for risk of (pre)malignant disease. Towards this aim genome-wide analyses of clinically annotated specimens of women with and without cervical disease are complemented with functional studies using in vitro model systems of HPV-transformed human keratinocytes.

(III) The role of HPV in non-cervical cancer
This research line aims to study the role of HPV in non-cervical carcinomas such as those of the penis, vulva, and ororespiratory tract.