Molecular heterogeneity of head and neck squamous cell carcinoma defined by next-generation sequencing.

Head and neck squamous cell carcinoma (HNSCC) can be divided into two different clinical entities based on their association with high-risk subtypes of human papilloma virus (HPV16 and HPV18). Dissimilarities in prognosis and molecular profiles have attracted much attention in recent years, in part because of increasing rates of HPV infection in HNSCC; however, the underlying mechanisms and detailed genetic profiles that set these tumors apart are still elusive. To elucidate oncogenic pathways in HNSCC with and without HPV infection, we used targeted next-generation sequencing to interrogate single-nucleotide polymorphisms (SNPs) in 50 cancer-related genes. We detected SNPs in 25 of these genes from HNSCC tissue specimens with and without HPV infection. In 5 of the 25 genes, variant patterns were similar regardless of HPV infection status. A greater number of sequence variants in genes from the tyrosine kinase receptors and their associated pathways were preferentially present in HPV(+) specimens. SNPs in genes related to tumor-suppressor functions were more prevalent in HPV(-) HNSCC specimens. The observations may help to elucidate mechanisms involved in the molecular pathogenesis of two clinically diverse subclasses of HNSCC. Over-representation of SNPs in either HPV(+) or HPV(-) HNSCC is another indicator of potentially actionable sequence variants for targeted therapy.