HPV+ group

Infections with high-risk human papillomaviruses (HPVs) are causative events for cervical cancer and subgroups of other anogenital cancers such as anal and vulva cancer. In the course of various projects, we are studying the impact of this finding at the level of cancer prevention, diagnostics, risk stratification and test of cure.

Renske Steenbergen

Our research builds on an imperative translational pipeline from the discovery of genetic and epigenetic mechanisms driving carcinogenesis, on to clinical validation of the resulting disease biomarkers.

Towards these goals we study both HPV-based cell culture models and clinical specimens (tissues, scrapes, self-collected cervicovaginal specimens and urine) by means of genome-wide and candidate gene approaches to identify relevant cellular alterations. Candidate biomarkers are subsequently evaluated on well-defined clinical sample series to determine the best test algorithm, followed by validation in clinical trials.

In adjunct to this HPV research line we expand our biomarker research (HPV+) to improve the early detection of other urogenital cancers, like endometrial and bladder cancer, using urine liquid biopsies.

Aims of the research program
1) To improve the effectiveness of the cervical and anal cancer screening programs.
2) To enable tailored treatment of HPV-induced premalignant anogenital disease (of the anus, cervix and vulva) by risk-stratification biomarkers.
3) To develop patient-friendly urine-based early detection methods for urogenital cancers, such as endometrial and bladder cancer.

Further information: www.hpvstudies.nl

Group members

Academic staff

  • Maaike Bleeker MD PhD
  • Renske Steenbergen Prof PhD (Program leader)

Postdocs

  • Kirsten Rozemeijer
  • Mariano Molina Beita
  • Shiva Najjary

PhD students

  • Irene Beijert MD
  • Fernando Dias Goncalves Lima MD
  • Mirte Schaafsma MD
  • Féline Voss MD
  • Mengfei Xu MD
  • Dominique de Vries MD
  • Flavia Runello
  • Mila Griffioen MD

Technicians

  • Timo ter Braak
  • Yara van den Burgt
  • Sylvia Duin
  • Annina van Splunter

                    Key publications

                    Huseinovic A, Xu M, Jaspers A, Bais B, Steenbergen RDM. miR-129-5p inhibits anchorage-independent growth through silencing of ACTN1 and the ELK4/c-FOS axis in HPV-transformed keratinocytes. J Med Virol. 2024 Apr;96(4):e29580. doi: 10.1002/jmv.29580.PMID: 38566572

                    Wever BMM, Steenbergen RDM. Unlocking the potential of tumor-derived DNA in urine for cancer detection: methodological challenges and opportunities. Mol Oncol. 2024 Mar 10. doi: 10.1002/1878-0261.13628. Online ahead of print. PMID: 38462745

                    Voss FO, Thuijs NB, Duin S, Özer M, van Beurden M, Berkhof J, Steenbergen RDM, Bleeker MCG. Clinical validation of methylation biomarkers for optimal detection of high-grade vulvar intraepithelial neoplasia. Int J Cancer. 2023 Apr 19. doi: 10.1002/ijc.34537. PMID:37074263

                    Wever BMM, van den Helder R, van Splunter AP, van Gent MDJM, Kasius JC, Trum JW, Verhoeve HR, van Baal WM, Hulbert A, Verhoef L, Heideman DAM, Lissenberg-Witte BI, van Trommel NE, Steenbergen RDM, Bleeker MCG. DNA methylation testing for endometrial cancer detection in urine, cervicovaginal self-samples and cervical scrapes.Int J Cancer. 2023 Mar 13. doi: 10.1002/ijc.34504. PMID: 36912267

                    Vink FJ, Meijer CJLM, Hesselink AT, Floore AN, Lissenberg-Witte BI, Bonde JH, Pedersen H, Cuschieri K, Bhatia R, Poljak M, Oštrbenk Valenčak A, Hillemanns P, Quint WGV, Del Pino M, Kenter GG, Steenbergen RDM, Heideman DAM, Bleeker MCG. FAM19A4/miR124-2 Methylation Testing and Human Papillomavirus (HPV) 16/18 Genotyping in HPV-Positive Women Under the Age of 30 Years. Clin Infect Dis. 2023 Feb 8;76(3):e827-e834. doi: 10.1093/cid/ciac433. PMID: 35686306

                    van den Helder R, Steenbergen RDM, van Splunter AP, Mom CH, Tjiong MY, Martin I, Rosier-van Dunné FMF, van der Avoort IAM, Bleeker MCG, van Trommel NE. HPV and DNA Methylation Testing in Urine for Cervical Intraepithelial Neoplasia and Cervical Cancer Detection. Clin Cancer Res. 2022 May 13;28(10):2061-2068. doi: 10.1158/1078-0432.CCR-21-3710. PMID: 35266975

                    Kremer WW, Dick S, Heideman DAM, Steenbergen RDM, Bleeker MCG, Verhoeve HR, van Baal WM, van Trommel N, Kenter GG, Meijer CJLM, Berkhof J. Clinical Regression of High-Grade Cervical Intraepithelial Neoplasia Is Associated With Absence of FAM19A4/miR124-2 DNA Methylation (CONCERVE Study). J Clin Oncol. 2022 May 5:JCO2102433. doi: 10.1200/JCO.21.02433. Online ahead of print. PMID: 35512257

                    van der Zee RP, Richel O, van Noesel CJM, Ciocănea-Teodorescu I, van Splunter AP, Ter Braak TJ, Nathan M, Cuming T, Sheaff M, Kreuter A, Meijer CJLM, Quint WGV, de Vries HJC, Prins JM, Steenbergen RDM. Cancer Risk Stratification of Anal Intraepithelial Neoplasia in Human Immunodeficiency Virus-Positive Men by Validated Methylation Markers Associated With Progression to Cancer. Clin Infect Dis. 2021 Jun 15;72(12):2154-2163. doi: 10.1093/cid/ciaa397. PMID: 32266940

                      Contact

                      r.steenbergen@amsterdamumc.nl
                      020-4442331

                      Keywords

                      HPV | biomarkers | risk-stratification | methylation | urine | anogenital cancer