Genetic alterations in head and neck squamous cell carcinoma: The next-gen sequencing era

Head and neck squamous cell carcinoma is the sixth most common cancer in the world with approximately 650000 new cases diagnosed annually. Next-generation molecular techniques and results from phase 2 of the Cancer Genome Atlas becoming available have drastically improved our current knowledge on the genetics basis of head and neck squamous cell carcinoma. New insights and new perspectives on the mutational landscape implicated in head and neck squamous cell carcinoma provide improved tools for prognostication. More importantly, depend on the patient’s tumor subtypes and prognosis, deescalated or more aggressive therapy maybe chosen to achieve greater potency while minimizing the toxicity of therapy. This paper aims to review our current knowledge on the genetic mutations and altered molecular pathways in head and neck squamous cell carcinoma. Some of the most common mutations in head and neck squamous cell carcinoma reported by the cancer genome atlas including TP53, NOTCH1, Rb, CDKN2A, Ras, PIK3CA and EGFR are described here. Additionally, the emerging role of epigenetics and the role of human papilloma virus in head and neck squamous cell carcinoma are also discussed in this review. The molecular pathways, clinical applications, actionable molecular targets and potential therapeutic strategies are highlighted and discussed in details.