Sequencing the head and neck cancer genome: implications for therapy.

Head and neck squamous cell carcinoma (HNSCC) is a disease with significant morbidity and mortality. The advancement of next-generation sequencing technologies now enables the landscape of genetic alterations in HNSCCs to be deciphered. In this review, we describe the mutation spectrum discovered in HNSCCs, especially human papilloma virus-associated and/or tobacco smoke exposure-associated HNSCCs. We also describe related research from two independent investigators and from the Cancer Genome Atlas. Emphasis is placed on the therapeutic implications of genes frequently altered in HNSCCs (i.e., TP53, PIK3CA, and NOTCH1) and their corresponding pathways, with a particular focus on recent findings of Notch signaling pathway activation in HNSCC. We also discuss the application of integrated genomic pathway-based analysis for precision cancer therapy in HNSCC.