Projects per year
Personal profile
Research interests
HPV-induced carcinogenesis
Research Background
Infections with high-risk human papillomaviruses (HPVs) are causative events for cervical cancer, and subgroups of other anogenital cancers. In the course of various projects, we are studying the impact of this finding at the level of cancer prevention, diagnostics, risk stratification, test of cure, and prophylactic vaccination.
Our research has further incorporated an important translational pipeline involving the discovery of (epi)genetic, molecular mechanisms driving carcinogenesis, and clinical validation of disease biomarkers that result therefrom.
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.
Aim of the research program
- Improving effectiveness of cervical cancer screening (focus on gaining >sensitivity (via HPV testing or other biomarkers), >compliance (via self-sampling), and >specificity (molecular disease biomarkers used as triage test of HPV positive women or direct primary screening test)
- Improving risk stratification by molecular biomarkers of patients with premalignant ano-genital disease (CIN, VIN, AIN) for tailored treatment.
- Development of novel early detection biomarkers for ano-genital cancers detectable in cervico-vaginal, anal and urine samples
Methodology
Identification and functional characterization of oncogenic events as a basis for the discovery of new candidate biomarkers:
- Specimens representing sequence from premalignant to malignant disease (tissues, cervical scrapings, self-samples)
- Longitudinal in vitro model systems of primary keratinocytes in which hrHPV types are introduced (functional characterization)
Verification and clinical validation of biomarkers:
- Stored specimens in biobanks
- Prospective clinical and screening trials
Novel non-invasive cancer detection methods
For a number of non-HPV-induced cancers, such as endometrial cancer, ovarian cancer, bladder cancer, lung cancer and colorectal cancer, molecular tests primarily based on DNA methylation are being developed to enable their (early) detection in urine. This line of research is conducted in close collaboration with the Depts of Gynaecology, Urology, Pulmonology and Surgery.
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
Education/Academic qualification
PhD, High-risk human papillomavirus-mediated carcinogenesis¬: an in vivo and in vitro analysis, VU University
1 May 1993 → 20 Jun 1997
Award Date: 20 Jun 1997
Master, Biomedical Sciences, Leiden University, Leiden, Netherlands
30 Sept 0001 → 19 Nov 1991
Award Date: 19 Nov 1991
External positions
Senior Scientific Officer, Self-screen B.V, Amsterdam, the Netherlands.
1 May 2008 → 31 Dec 3999
Keywords
- RB Pathology
- HPV, Oncology, biomarkers
Collaborations and top research areas from the last five years
Projects
- 1 Active
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RISCC: Risk-based screening for cervical cancer
Berkhof, H., Meijer, C., Kroon, K., Bogaards, H., Heideman, D., Steenbergen, R., Arbyn, M., Baussano, I., Bosch, X., Clifford, G. M., Dillner, J., Elfström, K. M., Georges, D., Lehtinen, M., Pimenoff, V. N., Poljak, M., Ronco, G., Vänskä, S. & Branquinho da Costa, S.
1/11/2019 → 31/12/2024
Project: Research
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Clinical validation of methylation biomarkers for optimal detection of high-grade vulvar intraepithelial neoplasia
Voss, F. L. O., Thuijs, N. B., Duin, S., Özer, M. J., van Beurden, M., Berkhof, J., Steenbergen, R. D. M. & Bleeker, M. C. G., 15 Aug 2023, In: International journal of cancer. 153, 4, p. 783-791 9 p.Research output: Contribution to journal › Article › Academic › peer-review
Open Access -
DNA methylation testing for endometrial cancer detection in urine, cervicovaginal self-samples and cervical scrapes
Wever, B. M. M., van den Helder, R., van Splunter, A. P., van Gent, M. D. J. M., Kasius, J. C., Trum, J. W., Verhoeve, H. R., van Baal, W. M., Hulbert, A., Verhoef, L., Heideman, D. A. M., Lissenberg-Witte, B. I., van Trommel, N. E., Steenbergen, R. D. M. & Bleeker, M. C. G., 15 Jul 2023, In: International journal of cancer. 153, 2, p. 341-351 11 p.Research output: Contribution to journal › Article › Academic › peer-review
Open Access1 Citation (Scopus) -
Downregulation of miR-193a/b-3p during HPV-induced cervical carcinogenesis contributes to anchorage-independent growth through PI3K-AKT pathway regulators
Xu, M., Huseinovic, A., Jaspers, A., Yuan, L. & Steenbergen, R. D. M., 1 Mar 2023, In: Journal of Medical Virology. 95, 3, p. e28589 e28589.Research output: Contribution to journal › Article › Academic › peer-review
Open Access -
Evaluation of DNA methylation biomarkers ASCL1 and LHX8 on HPV-positive self-collected samples from primary HPV-based screening
Verhoef, L., Bleeker, M. C. G., Polman, N., Steenbergen, R. D. M., Ebisch, R. M. F., Melchers, W. J. G., Bekkers, R. L. M., Molijn, A. C., Quint, W. G., van Kemenade, F., Meijer, C. J. L. M., Berkhof, J. & Heideman, D. A. M., 27 Jul 2023, In: British journal of cancer. 129, 1, p. 104-111 8 p.Research output: Contribution to journal › Article › Academic › peer-review
Open Access -
FAM19A4/miR124-2 Methylation Testing and Human Papillomavirus (HPV) 16/18 Genotyping in HPV-Positive Women Under the Age of 30 Years
Vink, F. J., Meijer, C. J. L. M., Hesselink, A. T., Floore, A. N., Lissenberg-Witte, B. I., Bonde, J. H., Pedersen, H., Cuschieri, K., Bhatia, R., Poljak, M., Oštrbenk Valenčak, A., Hillemanns, P., Quint, W. G. V., del Pino, M., Kenter, G. G., Steenbergen, R. D. M., Heideman, D. A. M. & Bleeker, M. C. G., 1 Feb 2023, In: Clinical Infectious Diseases. 76, 3, p. e827-e834Research output: Contribution to journal › Article › Academic › peer-review
Open Access2 Citations (Scopus)
Activities
- 1 Organising a conference, workshop, ...
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Eurogin
Renske Steenbergen (Participant)
11 Apr 2022Activity: Participating in or organising an event › Organising a conference, workshop, ... › Academic
Press/Media
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Geen uitstrijkje meer: urinetest moet deelname aan bevolkingsonderzoek baarmoederhalskanker verbeteren
18/10/2021
1 Media contribution
Press/Media: Public Engagement Activities
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URINETEST MOET ER VOOR ZORGEN DAT ARTSEN BAARMOEDERHALSKANKER EERDER OPSPOREN
14/10/2021
1 Media contribution
Press/Media: Public Engagement Activities
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KWF vrijwilligersavond Amstelveen
27/11/2018
1 Media contribution
Press/Media: Public Engagement Activities
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Alpe d'Huzes grant award for project "RNA modifying enzymes diversify the miRNA repertoire and function during early stage cancer development"
29/05/2017 → 2/06/2017
3 Media contributions
Press/Media: Public Engagement Activities