Molecular Biomarkers of Malignant Transformation in Head and Neck Dysplasia

Head and neck squamous cell carcinoma (HNSCC) and its treatments are associated with substantial morbidity, often resulting in cosmetic deformity and loss of physiologic functions including speech and swallowing. Despite advancements in treatment, 5-year survival rates for mucosal malignancies remain below 70%. Effective prevention of HNSCC demands an understanding of the molecular pathways of carcinogenesis. Specifically, defining features of pre-cancerous dysplastic lesions that indicate a better or worse prognosis is necessary to help identify patients who are likely to develop a carcinoma and allow a more aggressive approach to management. There remains a need for identification of biomarkers that can provide both early prognostic and predictive value in clinical decision-making by serving as both therapeutic targets as well as predictors of therapy response. Here, we comprehensively review the most frequently altered molecular biomarkers of malignant transformation in head and neck dysplasia. These markers are involved in a wide range of cellular processes in head and neck carcinogenesis, including extracellular matrix degradation, cell motility and invasion, cell-cell adhesion, solute transport, immortalization, metabolism, the cell cycle and apoptosis, transcription, and cell signaling.