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Does Pretreatment Seropositivity to Human Papillomavirus Have Prognostic Significance for Head and Neck Cancers?

Departments of ¹ Epidemiology and ² Biostatistics, College of Public Health, Departments of ³ Otolaryngology and ⁴ Pathology, College of Medicine, University of Iowa; ⁵ Veterans Affairs Medical Center, Iowa City, Iowa; and ⁶ Department of Experimental Virology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic

Requests for reprints: Elaine M. Smith, Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242. Phone: 319-384-5014; Fax: 319-384-5031. E-mail: elaine-smith{at}uiowa.edu

Background: Human papillomavirus (HPV) is a risk factor for head and neck cancers (HNC), yet HPV-associated tumors have better prognosis than HPV-negative tumors.

Methods: We evaluated whether pretreatment presence of antibodies to HPV capsids [virus-like particles (VLP)] or to HPV-16 oncoproteins E6 and E7 was a predictor of HPV-positive HNC and clinical outcomes. Sera from 156 HNC patients were tested for antibodies to HPV-16–derived antigens using ELISA. HPV-16 in tumors was evaluated by PCR and DNA sequencing.

Results: HPV-16 antibodies were found in 33% with HPV-16 VLP, 21% with HPV-16 E6, and 21% with E7. HPV-16 was detected in 26% of tumors. There was a strong correlation between detection of HPV-16 tumor DNA and antibodies to HPV-16 E6 or E7 ( = 0.7) but not to HPV-16 VLP ( = 0.4). Multivariate analyses showed significantly better disease-specific survival in seropositive HPV-16 VLP [hazard ratio (HR), 0.4; 95% confidence interval (95% CI), 0.1-0.9], HPV-16 E6 (HR, 0.1; 95% CI, 0.02-0.5), and HPV-16 E7 (HR, 0.3; 95% CI, 0.1-0.9) cases. Less disease recurrence occurred among those with antibodies to both E6 and E7 compared with those negative to both (P = 0.003). There was better disease-specific survival in patients who were E6 positive at baseline and remained positive at follow-up compared with individuals who were E6 negative at both time points (P = 0.03; = 0.9).

Conclusions: The presence of antibodies to HPV-16 E6 and E7 is associated with HPV in tumor cells and with better clinical outcomes. These findings suggest that the presence of E6/E7 antibodies before treatment is predictive of better clinical outcomes and that they may serve as biomarkers for selecting targeted therapeutic modalities developed for HPV-associated tumors. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2087–96)