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Human papillomavirus serologic follow-up response and relationship to survival in head and neck cancer: a case-comparison study

Linda M Rubenstein1*, Elaine M Smith1, Michael Pawlita2, Thomas H Haugen3, Eva Hamšíková4 and Lubomir P Turek3

Author Affiliations

1 Department of Epidemiology College of Public Health, University of Iowa, Iowa City, IA 52242, USA

2 Research Program infection and Cancer German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany

3 Veterans Affairs Medical Center and Department of Pathology, College of Medicine, University of Iowa, Iowa City, IA 52242, USA

4 Department of Experimental Virology Institute of Hematology and Blood Transfusion, Prague, Czech Republic

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Infectious Agents and Cancer 2011, 6:9  doi:10.1186/1750-9378-6-9

Published: 8 July 2011



Human papillomavirus high risk (HPV-HR) type 16 is a significant risk factor for head and neck cancers (HNC) independent of tobacco and alcohol. The purpose of this study was to determine whether antibody levels to the HPV-16 oncoproteins E6 and E7 measured in sera collected at baseline (BL) prior to treatment and at two post-treatment follow-up (FU) visits were associated with HNC risk factors or prognosis.


Presence of antibodies to HPV-16 E6 and E7 was evaluated in 109 newly diagnosed HNC cases with BL and FU blood samples, using the enzyme-linked immunosorbent assay (ELISA).


HPV-16 E6 and/or E7 seropositive HNC cases were associated with higher risk in younger patients (≤ 55 years), more sexual partners (≥ 10), oropharyngeal cancer, worse stage at diagnosis, poorer grade, and nodal involvement. Between BL and FU (median = 8.3 months), there were decreased antibody levels for seropositive E6 (73% vs. 27%, p = 0.02) and seropositive E7 patients (65% vs. 35%, p = 0.09) with 5% of BL E6 and 35% of BL E7 seropositive patients converting to negative status at FU. Overall mortality (OM) was significantly worse among BL E6 seronegative patients than among BL seropositive patients (40.2% vs.13.6%, p = 0.01). There were no disease specific (DS) deaths among BL E6 seropositive vs. 24% in BL E6 seronegative patients (p = 0.01). BL E7 seronegative patients also had higher mortality than BL seropositive patients (OM: 38.2% vs. 20.0%, p = 0.04; DS: 22.5% vs. 5.6%, p = 0.07).


These findings are the first to follow post-treatment OD levels of HPV-16 E6 and E7 in HNC and suggest that these HPV antibodies may be potential prognostic markers of survival in HNC patients.

head and neck neoplasms; human papillomavirus; HPV-16 E6/E7