Hypoxia-inducible Factors HIF-1 and HIF-2 in Head and Neck Cancer: Relationship to Tumor Biology and Treatment Outcome in Surgically Resected Patients

Hypoxia within head and neck squamous cell carcinoma (HNSCC) predicts a poor response to radiotherapy and poor prognosis. Hypoxiainducible factor (HIF)-1 and HIF-2 are nuclear transcription factors that regulate the cellular response to hypoxia and are important for solid tumor growth and survival. Overexpression of HIF-1 and HIF-2 was demonstrated in three HNSCC cell lines under hypoxia and tumor tissue versus normal tissue (n 20, HIF-1 , P 0.023; HIF-2 , P 0.013). On immunostaining, HIF-1 and HIF-2 expression were localized to tumor nuclei; HIF-2 expression was also seen in tumor-associated macrophages. Expression of HIF-1 in surgically treated patients with HNSCC (n 79) was associated with improved disease-free survival (P 0.016) and overall survival (P 0.027).