The Molecular Basis and Biomarker Potential of the HIF-1α–VEGF–GLUT1 Hypoxia Axis in Laryngeal Squamous Cell Carcinoma

In laryngeal squamous cell carcinoma, hypoxia plays a major role in growth, spread, and treatment resistance. HIF-1α, VEGF, and GLUT1 are three linked biomarkers that show different aspects of this response. Low oxygen can be sensed by HIF-1α, and it follows up by activating genes that help with the survival of the tumour cells. VEGF helps to form new blood vessels, while GLUT1 increases the uptake of glucose and maintains the production of energy even when there is a lack of oxygen. Tissue and serum studies have reported higher levels of these biomarkers in malignant than in benign or normal samples, together with associations with adverse clinicopathological features. However, their diagnostic and prognostic utility remains exploratory because clinically validated thresholds, diagnostic performance measures, and independent prospective validation remain limited. Combined assessment of these biomarkers may provide complementary information on hypoxic signalling, angiogenesis and metabolic adaptation, although its diagnostic or prognostic superiority over individual biomarkers has not yet been established. However, serum measurements can be influenced by pre-analytical and systemic factors. So, in order for these biomarkers to advance enough to be used in clinical laryngology, large multicenter studies and a standardized set of testing methods will be necessary.