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Division of Infections and Cancer Epidemiology

Dr. Tim Waterboer

About 20% of all cancer cases worldwide are associated with infections. The main etiologic agents are

  • Human Papillomaviruses (HPV) which are associated with cervical and other anogenital (e.g. anal) cancers, and head and neck, especially oropharyngeal cancer
  • Helicobacter pylori (H. pylori), a bacterium that causes gastric cancer
  • Hepatitis B and C viruses (HBV, HCV) which cause hepatocellular carcinoma
  • Epstein-Barr virus (EBV) which is associated with Hodgkin’s and Non-Hodgkin’s lymphoma and nasopharyngeal carcinoma
  • Human Herpesvirus 8 (HHV8), or Kaposi sarcoma-associated herpesvirus (KSHV), causing Kaposi sarcoma
However, the number of cancer cases attributable to infections is likely underestimated, and most of the infectious agents mentioned above may also cause other cancers, e.g. HPV and non-oropharyngeal head and neck cancer, or H. pylori and other gastrointestinal cancers. Moreover, additional infectious agents have been associated with cancer development, e.g. Chlamydia trachomatis and ovarian cancer.

The central aim of the Division is the secondary prevention, i.e. screening and early detection of infection-associated cancers, and combines molecular diagnostic approaches with population-based research. To this end, we combine proteomics, bioinformatics, high-throughput multiplexed immunoassays and advanced nucleic acid detection systems to discover prognostic and predictive biomarkers (such as antibodies against infectious agents from peripheral blood, or the pathogens’ nucleic acids in liquid biopsies) and validate them in large epidemiological cohort studies. Our aim is to translate our findings in prospective clinical and screening studies, and to thoroughly evaluate their public health impact.

One central technology in the Division is a high-throughput serological method (“Multiplex Serology”, “Serolomics”), which allows analyzing up to 2000 serum samples per day for antibodies to up to 100 different antigens simultaneously. We collaborate worldwide with many clinical and epidemiological partners to analyze large-scale seroepidemiological studies, and have successfully developed serological assays for all infectious agents mentioned above, and many others:

  • HPV
  • Helicobacter pylori
  • Human Polyomaviruses
  • Hepatitis B and C viruses
  • Human Herpesviruses HSV-1 and -2, VZV, CMV, EBV, and KSHV
  • Retroviruses HIV, HTLV-1
  • Chlamydia trachomatis
  • Rubella, Tetanus, Diphteria
  • Mycoplasma genitalium
  • Streptococcus gallolyticus
  • Fusobacterium nucleatum
  • Parvovirus B19
  • Treponema pallidum
  • Coxiella burnetii
  • as well as many tumor-associated antigens to measure auto-antibodies involved in e.g. colorectal carcinoma, ovarian cancer, or Multiple Sclerosis
In addition to multiplex serology, we develop PCR-based nucleic acid detection methods for application in tissue samples and other specimens (e.g., digital PCR for HPV and EBV liquid biopsies), and whole proteome microarrays of bacteria (e.g., C. trachomatis, H. pylori) for de novo biomarker identification.

Contact

Dr. Tim Waterboer
Infections and Cancer Epidemiology (F020)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 4948

Selected Publications

  • Mentzer AJ*, Brenner N*, Allen N, Littlejohns TJ, Chong AY, Cortes A, Almond R, Hill M, Sheard S, McVean G; UKB Infection Advisory Board, Collins R, Hill AVS, Waterboer T. Identification of host-pathogen-disease relationships using a scalable multiplex serology platform in UK Biobank. Nat Commun 13(1):1818 (2022).
  • Busch CJ, Hoffmann AS, Viarisio D, Becker BT, Rieckmann T, Betz C, Bender N, Schroeder L, Hussein Y, Petersen E, Jagodzinski A, Schäfer I, Burandt E, Lang Kuhs K, Pawlita M, Waterboer T*, Brenner N*. Detection of stage I HPV-driven oropharyngeal cancer in asymptomatic individuals in the Hamburg City Health Study using HPV16 E6 serology - A proof-of-concept study. EClinicalMedicine 53:101659 (2022).
  • Ferreiro-Iglesias A, McKay JD, Brenner N, Virani S, Lesseur C, Gaborieau V, Ness AR, Hung RJ, Liu G, Diergaarde B, Olshan AF, Hayes N, Weissler MC, Schroeder L, Bender N, Pawlita M, Thomas S, Pring M, Dudding T, Kanterewicz B, Ferris R, Thomas S, Brhane Y, Díez-Obrero V, Milojevic M, Smith-Byrne K, Mariosa D, Johansson MJ, Herrero R, Boccia S, Cadoni G, Lacko M, Holcátová I, Ahrens W, Lagiou P, Lagiou A, Polesel J, Simonato L, Merletti F, Healy CM, Hansen BT, Nygård M, Conway DI, Wright S, Macfarlane TV, Robinson M, Alemany L, Agudo A, Znaor A, Amos CI, Waterboer T*, Brennan P*. Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer. Nat Commun 12(1):5945 (2021).
  • Waterboer T, Brenner N, Gallagher R, Hillman RJ, Jin F, Grulich A, Poynten IM. Early Detection of Human Papillomavirus-Driven Oropharyngeal Cancer Using Serology From the Study of Prevention of Anal Cancer. JAMA Oncol 6(11):1806-8 (2020).
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