Poor prognosis in human papillomavirus-positive oropharyngeal squamous cell carcinomas that overexpress hypoxia inducible factor-1alpha.

BACKGROUND: Hypoxia induces stabilization of the transcription factor HIF-1alpha (HIF-1alpha), associated with (chemo-)radiotherapy resistance in oropharyngeal squamous cell carcinoma (SCC). We investigated the effect of HIF-1alpha expression on survival in relation to human papillomavirus (HPV) status in oropharyngeal SCC. METHODS: We conducted an immunohistochemical analysis of HIF-1alpha protein expression and downstream targets carbonic anhydrase-IX (CA-IX) and glucose transporter-1 (GLUT-1) in 274 patients with oropharyngeal SCC. Overall survival (OS) was analyzed in total and stratified for HPV status and treatment. RESULTS: In HPV-positive tumors (n = 44), HIF-1alpha overexpression predicted worse OS (hazard ratio [HR] = 6.23; p = .012), whereas TNM classification or treatment modality did not. In HPV-negative tumors (n = 218), advanced T and N classification and HIF-1alpha overexpression all independently predicted worse OS. However, the effect of HIF-1alpha overexpression on OS was lower in HPV-negative (HR = 1.50; p = .024) than in HPV-positive tumors. CONCLUSION: HIF-1alpha overexpression is associated with worse OS and characterized a subgroup of patients with HPV-positive oropharyngeal SCC with poor prognosis. Possibly, patients with HIF-1alpha overexpressing HPV-positive tumors should not be eligible for treatment dose deescalation. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1338-1346, 2016.