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

• Published in: Head & neck 2016-09, Vol.38 (9), p.1338-1346
• Main Authors: Swartz, Justin Egidius, Pothen, Ajit Joe, van Kempen, Pauline Maria Wilhelmina, Stegeman, Inge, Formsma, Fleurieke Karlijn, Cann, Ellen Maria Van, Willems, Stefan Martin, Grolman, Wilko
• Format: Article
• Language: English
• Subjects: Academic Medical Centers; Aged; biomarkers; Biomarkers, Tumor - analysis; Biopsy, Needle; Carcinoma, Squamous Cell - blood; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - virology; Databases, Factual; Female; Head and Neck Neoplasms - blood; Head and Neck Neoplasms - mortality; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - virology; Human papillomavirus; Humans; hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Immunohistochemistry; Male; Middle Aged; Netherlands; oropharyngeal carcinoma; Oropharyngeal Neoplasms - blood; Oropharyngeal Neoplasms - mortality; Oropharyngeal Neoplasms - pathology; Oropharyngeal Neoplasms - virology; Papillomaviridae - isolation & purification; Prognosis; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Survival Analysis; tumor microenvironment
• ISSN: 1043-3074; 1097-0347
• DOI: 10.1002/hed.24445

Background Hypoxia induces stabilization of the transcription factor HIF‐1alpha (HIF‐1α), associated with (chemo‐)radiotherapy resistance in oropharyngeal squamous cell carcinoma (SCC). We investigated the effect of HIF‐1α expression on survival in relation to human papillomavirus (HPV) status in oropharyngeal SCC. Methods We conducted an immunohistochemical analysis of HIF‐1α 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‐1α 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‐1α overexpression all independently predicted worse OS. However, the effect of HIF‐1α overexpression on OS was lower in HPV‐negative (HR = 1.50; p = .024) than in HPV‐positive tumors. Conclusion HIF‐1α overexpression is associated with worse OS and characterized a subgroup of patients with HPV‐positive oropharyngeal SCC with poor prognosis. Possibly, patients with HIF‐1α overexpressing HPV‐positive tumors should not be eligible for treatment dose deescalation. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1338–1346, 2016