Abstract

Abstract Background: Human papillomaviruses (HPVs) have been causally associated with several types of human cancers. With the path breaking discovery of the effective prophylactic HPV vaccine against cervical cancer, it is in public health interest to interrogate the possibility of expanding this vaccine to other HPV-associated cancers including head and neck squamous cell carcinoma (HNSCC). A major limitation is the limited number of studies in this field and a wide range of HPV detection rates, measured by various methodologies. Objectives: (1) To determine the status of HPV and its genotypes in HNSCC using highly sensitive assays; (2) To correlate these with clinical and pathologic variables to develop a clinical algorithm for risk stratification of HNSCC patients. Experimental procedures: DNA from 385 HNSCC formalin-fixed, paraffin embedded (FFPE) tissue blocks which were identified through a population-based cancer registry in Metropolitan Detroit were interrogated for HPV status using a sensitive broad-spectrum PCR technique specifically suitable for FFPE samples (DNA Enzyme Immuno Assay, followed by Line Probe Assay broad-spectrum assay). Clinical and pathologic variables obtained from the registry database were correlated with the HPV status. Results: HPV positivity was detected in 113 (29.35%) HNSCC cases, high risk genotype HPV 16 in 90 (79.65%) cases; HPV 18 in 2(1.77%) cases, dual HPV 16 & 18 in 3 (2.65%) cases and low risk HPV 6 in 2(1.77%) cases. Of the 81 oropharyngeal cases, 50.6% were HPV positive and 45.7 % were HPV 16 positive (p=<0.001). Correlation of HPV and high risk genotype HPV 16 with age, gender, race, marital status, tumor stage, tumor differentiation were not statistically significant. Hazard ratios (HR) and 95% confidence intervals (CI) for deaths from any causes in oropharyngeal SCC were 0.52 (0.23-1.17) for the patients positive to any HPV type and 0.34 (0.14-0.80) for those positive to HPV 16. Smoking or history of respiratory disease increases the risk of death in HNSCC irrespective of HPV status; however if smokers have HPV 16, their risk of dying is 33% lower than those without; however in non-smokers there was no protective effect of HPV16. Conclusions: HPV is present in ∼ 30% of HNSCC cases of which high risk genotype 16 comprises ∼ 80%. There is statistically significant positivity of HPV and high risk genotype 16 in the oropharyngeal cancers. There is no significant correlation between HPV status and age, gender, race, marital status, tumor stage and tumor differentiation in HNSCC. In the oropharyngeal SCC, HPV positivity reduces mortality by half and high risk genotype 16 reduces mortality by two-thirds. However, the protective effect of HPV on survival was only apparent in smokers or patients with history of respiratory disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3201. doi:10.1158/1538-7445.AM2011-3201

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