SPP1 and neoplasm: 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.