Kliniken & Institute … Institute Pathologisches Institut… Angewandte… Forschung HPV-assoziierte Tumoren… Biomarker und…

Biomarker-based early detection and prevention


Our research revealed that expression of the HPV E6-E7 oncogenes results in strong overexpression of the p16INK4a protein.

What we do

In frame of a spin off company (mtm-laboratories) we developed diagnostic tools to detect these cells in clinical samples and established cancer early detection kits that now allow to specifically detect each single cell transformed by HPV. In 2011 Roche acquired mtm-laboratories and is now further developing and validating the p16INK4a based biomarker concept world wide as CINtec and CINtec PLUS product lines.

In various projects we evaluate the clinical performance of p16INK4a as diagnostic and prognostic biomarker for cancers of different anatomic locations.

In collaboration with the British Columbia Cancer Research Center in Vancouver, Canada and support of the Else Kröner-Fresenius-Stiftung, we explore the significance of papillomaviruses in oral dysplasia (SiPOD study). The purpose of the SiPOD study is to learn about the biologic characteristics of HPV in oral premalignant lesions (OPL) and to more thoroughly classify OPL based on a potentially HPV-underlying carcinogenic pathway. This will be the essential to refine the molecular classification of OPL and to thereby improve progression risk prediction and treatment strategies.

For our efforts on cervical cancer screening see  ETiCCS and on head and neck cancer see  HOCC.

Key publications

  • Prigge ES, Arbyn M, von Knebel Doeberitz M, Reuschenbach M. Diagnostic accuracy of p16INK4a immunohistochemistry in oropharyngeal squamous cell carcinomas: A systematic review and meta-analysis. Int J Cancer. 2017 Mar 1;140(5):1186-1198.
  • von Knebel Doeberitz M. The causal role of human papillomavirus infections in non-anogenital cancers. It's time to ask for the functional evidence. Int J Cancer. 2016 Jul 1;139(1):9-11. .
  • Mai S, Welzel G, Ottstadt M, Lohr F, Severa S, Prigge ES, Wentzensen N, Trunk MJ, Wenz F, von Knebel Doeberitz M, Reuschenbach M. Prognostic Relevance of HPV Infection and p16 Overexpression in Squamous Cell Anal Cancer. Int J Radiat Oncol Biol Phys. 2015 93, 819-27.
  • Bergeron C, Ronco G, Reuschenbach M, Wentzensen N, Arbyn M, Stoler M, von Knebel Doeberitz M. The clinical impact of using p16(INK4a) immunochemistry in cervical histopathology and cytology: an update of recent developments. Int J Cancer. 2015 Jun 15;136(12):2741-51.
  • Prigge ES, Toth C, Dyckhoff G, Wagner S, Müller F, Wittekindt C, Freier K, Plinkert P, Hoffmann J, Vinokurova S, Klussmann JP, von Knebel Doeberitz M, Reuschenbach M. p16(INK4a) /Ki-67 co-expression specifically identifies transformed cells in the head and neck region. Int J Cancer. 2015 Apr 1;136(7):1589-99.
  • Koerber SA, Schoneweg C, Slynko A, Krug D, Haefner MF, Herfarth K, Debus J, Sterzing F, von Knebel Doeberitz M, Prigge ES, Reuschenbach M. Influence of human papillomavirus and p16INK4a on treatment outcome of patients with anal cancer. Radiother Oncol. 2014 Dec;113(3):331-6.
  • Reuschenbach M, Wentzensen N, Dijkstra MG, von Knebel Doeberitz M, Arbyn M. p16INK4a Immunohistochemistry in Cervical Biopsy Specimens: A Systematic Review and Meta-Analysis of the Interobserver Agreement. Am J Clin Pathol. 2014 Dec;142(6):767-72.
  • Reuschenbach M, Seiz M, von Knebel DC, Vinokurova S, Duwe A, Ridder R, Sartor H, Kommoss F, Schmidt D, von Knebel Doeberitz  M. Evaluation of cervical cone biopsies for coexpression of p16INK4a and Ki-67 in epithelial cells. Int J Cancer 2012 Jan 15;130(2):388-94.
  • von Knebel Doeberitz M, Reuschenbach M, Schmidt D, Bergeron C. Biomarkers for  cervical cancer screening: the role of p16(INK4a) to highlight transforming HPV infections. Expert Rev Proteomics. 2012 Apr;9(2):149-63.