So far, screening for hypoxic signatures in HNSCC revealed several tissue biomarkers, including HIF-1α, HIF-2α, carbonic anhydrase IX, GLUT1, and osteopontin [35]; however, these markers depend on the histological evaluation of tumor tissue and may only give information about the local oxygenation status, rather than capturing the heterogenous hypoxic landscape present in HNSCC. This evidence concerns the gene CA9 and head and neck squamous cell carcinoma.