Does pretreatment seropositivity to human papillomavirus have prognostic significance for head and neck cancers?
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 (kappa = 0.7) but not to HPV-16 VLP (kappa = 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; kappa = 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.
Smith
Elaine M
EM
Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242, USA. elaine-smith@uiowa.edu
Rubenstein
Linda M
LM
Ritchie
Justine M
JM
Lee
John H
JH
Haugen
Thomas H
TH
Hamsikova
Eva
E
Turek
Lubomir P
LP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood*; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000628:therapy / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000097:blood / Q000821:virology*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D012097:Repressor Proteins; D012307:Risk Factors; D018709:Statistics, Nonparametric; D016019:Survival Analysis
D000914:Antibodies, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16