Article
Prognostic significance of HPV-16 serologic markers in head and neck squamous cell carcinoma
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Published: | September 20, 2011 |
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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.
References
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