gms | German Medical Science

MAINZ//2011: 56. GMDS-Jahrestagung und 6. DGEpi-Jahrestagung

Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e. V.
Deutsche Gesellschaft für Epidemiologie e. V.

26. - 29.09.2011 in Mainz

Prognostic significance of HPV-16 serologic markers in head and neck squamous cell carcinoma

Meeting Abstract

  • Tim Waterboer - DKFZ, Heidelberg
  • Caihua Liang - Brown University, Providence, RI, USA
  • Carmen J. Marsit - Brown University, Providence, RI, USA
  • Michael D. McClean - Boston University, Boston, MA, USA
  • Heather H. Nelson - University of Minnesota, Minneapolis, MN, USA
  • Michael Pawlita - DKFZ, Heidelberg
  • Karl T. Kelsey - Brown University, Providence, RI, USA

Mainz//2011. 56. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds), 6. Jahrestagung der Deutschen Gesellschaft für Epidemiologie (DGEpi). Mainz, 26.-29.09.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11gmds207

doi: 10.3205/11gmds207, urn:nbn:de:0183-11gmds2071

Published: September 20, 2011

© 2011 Waterboer et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Background: It has been shown that Human Papillomavirus (HPV) type 16 (HPV-16) is associated with head and neck squamous cell carcinoma (HNSCC), with a preponderance of the infection-associated tumors arising in the oropharynx. Other risk factors for HNSCC include tobacco and alcohol consumption. Detection of HPV-16 DNA in tumors has been associated with improved prognosis; however, few studies have investigated antibody responses to HPV in HNSCC patients. We have studied 488 HNSCC patients (196 oral cavity, 199 oropharynx, and 92 larynx cancers) and 540 population-based matched controls, examining the relationship of seropositivity to early (E) and late (L) gene products with disease risk and survival.

Methods: Blinded sera were assayed for antibodies to the HPV-16 E6 and E7 oncoproteins and the L1 capsid protein using multiplex HPV serology [1]. Statistical analyses included logistic regression, Kaplan Meier survival plots, and Cox regression.

Results: Antibody responses to HPV-16 E6, E7 and L1 were strongly associated with HNSCC. Stratified by disease site, 54-fold, 36-fold and 20-fold increased disease risks were found for oropharyngeal cancer, respectively. Serologic associations with oral cavity and larynx cancers were approx. 4-fold and 2-fold, respectively. Site-specific cancer risks were 3- to 4-fold higher in HPV-16 seropositive never (versus ever) tobacco smokers and low-dose (versus high-dose) alcohol drinkers. The presence of early gene antibodies was also associated with significantly enhanced survival, with Hazard Ratios in the range of 0.2.

Conclusion: Detection of HPV16-specific early gene antibodies is a highly sensitive and specific marker of HNSCC risk and survival. The data also imply different HNSCC entities, driven either by HPV infection, or by alcohol and tobacco consumption.


Waterboer T, Sehr P, Michael KM, Franceschi S, Nieland JD, Joos TO, Templin MF, Pawlita M. Multiplex human papillomavirus serology based on in situ-purified glutathione s-transferase fusion proteins. Clin Chem. 2005;51(10):1845-53.