Hypoxia in head and neck cancer: current relevance

Abstract

Hypoxia is a common characteristic of solid tumors, typically resulting from abnormal and inefficient tumor vasculature that fails to meet the high oxygen demands of rapidly dividing tumor cells. While healthy tissues generally maintain oxygen levels around 5%, most tumors exhibit median oxygen levels below 1%, a condition known to cause radioresistance. This observation has led to efforts to reverse tumor hypoxia or, alternatively, to exploit the hypoxic environment to ensure selective cytotoxicity of drugs, particularly in the context of head and neck squamous cell carcinoma (HNSCC). Nimorazole is one such hypoxia-activated compound that is at the center of a lively debate surrounding clinical trials conducted 25 years apart. At the edge of this passionate discussion, the higher radiosensitivity of HPV-positive oropharyngeal carcinoma (compared to HPV-negative HNSCC) presents an intriguing opportunity to identify molecular determinants of therapeutic response. Additionally, the resurgence of studies investigating tumor metabolism has brought renewed attention to strategies that combat hypoxia not by providing external oxygen, but by inhibiting cancer cell respiration. Ultimately, these insights underscore the potential for innovative treatments to improve HNSCC patient outcomes