The prognostic significance of hypoxia inducing factor 1-α in oropharyngeal cancer in relation to human papillomavirus status

Objectives: This study examines the prognostic significance of hypoxia inducing factor-1 alpha (HIF-1 alpha) expression in relation to human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (SCC). Materials and methods: Clinical details on 233 oropharyngeal SCCs were extracted from institutional databases. Recurrence in any form or death from any cause was recorded for a median of 51 months after diagnosis. HIF-1 alpha expression was evaluated by semiquantitative immunohistochemistry and HPV status was determined by HPV E6-targeted multiplex real-time PCR and p16 immunohistochemistry. Determinants of recurrence and mortality hazards were modeled using Cox regression with censoring at dates of last follow-up. Results: The HIF-1 alpha positivity rate was 58.8%. HIF-1 alpha positivity was associated with higher T category (T3/T4 vs. T1/T2, 64.2% vs. 48.4%, p = 0.001) and lower grade (Grade 1-2 vs. 3, 62% vs. 46.9%, p = 0.001). There was no significant association between HIF-1 alpha expression and HPV status. After adjustment for clinico-pathological variables, HPV status but not HIF-1 alpha was a strong predictor of outcome. The combination of HPV and HIF-1 alpha was not a prognostic variable but the worst outcomes were seen in those with HPV negative and HIF-1 alpha positive cancers. There was no statistically significant evidence of an interaction between HPV and HIF-1 alpha. Conclusions: The degree of hypoxia as measured by HIF-1 alpha expression does not differ between HPV positive and HPV negative cancers. The role of hypoxia in HPV negative oropharyngeal cancer warrants further investigation. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.