HPV-induced cancer

The Molecular Pathology Unit of the Department of Pathology studies the biology of human papillomavirus (HPV)-induced carcinogenesis. Infections with high-risk human papillomaviruses (HPVs) can cause cervical cancer as well as subgroups of other anogenital cancers and head-and-neck cancers. However, most HPV infections are clinically irrelevant and not all HPV-induced precancerous lesions progress to cancer. An in depth understanding of the biology underlying HPV-induced carcinogenesis is needed to enable risk stratification of HPV-infected individuals.
Hereto, we have developed a comprehensive translational pipeline incorporating in vitro model systems, well defined clinical specimens and prospective clinical trials. 
Ultimately we aim to:

To achieve these goals a highly interdisciplinary research team consisting of molecular biologists, clinicians and biostatisticians has been established.
Towards these goals we are analysing specimens of patients with anogenital (pre)malignant disease (e.g. cervix, vulva, penis and anus) using to genome-wide screens and candidate gene approaches to identify relevant cellular alterations. Using in vitro studies on HPV-transformed human keratinocytes we 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. Functional data from these model systems are used to complement studies on clinical samples to select the most promising biomarkers for risk stratification of premalignant disease. The candidate markers that result from these studies are subsequently evaluated on clinical sample series in order to select the best classifier and test algorithm. Finally, candidates are clinically validated, amongst others for their value in primary cervical screening using both cervical scrapings and self-collected (cervico-)vaginal samples.
 For further information please visit www.hpvstudies.nl

Acadamic staff

Maaike Bleeker MD PhD  
Daniëlle Heideman PhD  
Chris Meijer MD PhD   
Renske Steenbergen PhD - (deputy program leader)

Postdocs   

Lise de Strooper -  PhD 
Putri Novianti -  PhD
Dorian Swarts  - PhD 
Linping Hui -  PhD

PhD students 

Iris Babion
Nicole Polman MD
Barbara Snoek
Wina Verlaat
Marjolein van Zummeren MD
Wieke Kremer MD (research fellow)
Ramon van der Zee

PhD Theses

2017

Uijterwaal, M.H. (2017, January 9). Novel biomarkers for cervical screening and survaillance of women treated for cervical precancer. VU University Amsterdam. 
Promotors: prof.dr. C.J.L.M. Meijer, prof.dr. Th.J.M. Helmerhorst 
Copromotors: dr. R.D.M. Steenbergen, dr. J. Berkhof

2016 

Schütze, D.M. (2016, May 19).The Road to HPV-Induced Keratinocyte Eternity: Molecular Characterization of HPV-Type Dependent In Vitro Immortalization. VU University Amsterdam. 
Promotors: prof.dr. P.J.F. Snijders, prof.dr. C.J.L.M. Meijer
Copromotors: dr. R.D.M. Steenbergen, dr. W.G.V.Quint 

De Strooper, L.M.A. (2016, February 5). Methylation analysis for the management of HPV-positive women. VU University Amsterdam. 
Promotors: prof.dr. P.J.F. Snijders, prof.dr. C.J.L.M. Meijer
Copromotors: dr. D.A.M. Heideman & dr. R.D.M. Steenbergen.  

2014

Verhoef, V.M.J. (2014, December 10). Improving cervical cancer screening by HPV self-sampling. VU University Amsterdam. 
Promotors: prof.dr. C.J.L.M. Meijer, prof.dr. P.J.F. Snijders 
Copromotors: prof.dr. F.J. van Kemenade & dr. L. Rozendaal.

van Baars, R. (2014, October 1) Improving cervical cancer prevention by HPV self-sampling, colposcopy and biomarkers. Erasmus University Rotterdam. 
Promotors: prof.dr. Th.M Helmerhorst, prof.dr. P.J.F. Snijders
Copromotors: dr. W.G.V. Quint, dr. W.A. ter Harmsel.

Snellenberg, S. (2014, July 01). Uncovering epigenetic alterations of tumour suppressor and viral genes during HPV-induced cervical carcinogenesis. VU University Amsterdam. 
Promotors: prof.dr. P.J.F. Snijders, prof.dr. C.J.L.M. Meijer
Copromotors: dr. R.D.M. Steenbergen & prof.dr.ir. W.M.R. van Criekinge.

Dijkstra, M.G. (2014, May 19). Towards a more objective way of cervical cancer screening: cervical cancer screening 2.0. VU University Amsterdam. 
Promotors: prof.dr. C.J.L.M. Meijer, prof.dr. P.J.F. Snijders
Copromotors: dr. W.M. van Baal & prof.dr. F.J. van Kemenade.

Rietbergen, M.M. (2014, May 7). The role of human papillomavirus in head and neck cancer. VU University Amsterdam. 
Promotors: prof.dr. R. Brakenhoff, prof.dr. C.R. Leemans, prof.dr. P.J.F. Snijders
Copromotor: prof.dr. E Bloemena

Mollers, M. (2014, April 22). Monitoring the impact of HPV vaccination: pre- and early post-vaccination data. VU University Amsterdam. 
Promotor: prof. dr. C.J.L.M. Meijer
Copromotor: dr. H.E. de Melker

2013

Scherpenisse, M. (2013, October 17). The humoral immune responses after HPV infection and prophylactic vaccination: importance of serology. VU University Amsterdam. 
Promotor: prof.dr. C.J.L.M. Meijer
Copromotors: dr. F.R.M. van der Klis, dr. G.A.M. Berbers.

Cornet, I. (2013, March 14) Studies on mucosal and cutaneous HPV types: the role of genotypes and natural variants in determining their potential oncogenicity. VU University Amsterdam. 
Promotor: prof.dr. P.J.F. Snijders
Copromotor: dr. M. Tommasino.

Rijkaart, D.C. (2013, March 1). Impact of HPV testing on cervical cancer screening. VU University Amsterdam. 
Promotors: prof.dr. C.J.L.M. Meijer, prof.dr. P.J.F. Snijders
Copromotors: dr. J. Berkhof, dr. D.A.M. Heideman

Bierkens M. (2013, January 22). Understanding the heterogeneity of high-grade CIN lesions: chromosomal and epigenetic analysis. 
Promotors: prof.dr. P.J.F. Snijders, prof.dr. C.J.L.M. Meijer
Copromotor: dr. R.D.M. Steenbergen

Student projects

For research internships please contact 
Dr. R.D.M. Steenbergen, r.steenbergen@vumc.nl

For internships on molecular diagnostics please contact 
Dr. D.A.M. Heideman, dam.heideman@vumc.nl