The Genome-Wide Molecular Landscape of HPV-Driven and HPV-Negative Head and Neck Squamous Cell Carcinoma

Recent advances in sequencing technology have enabled unprecedented genome-wide characterization of head and neck squamous cell carcinoma (HNSCC). Integrated analyses of publicly available multiplatform high-throughput data have uncovered the vast genomic, epigenetic, and transcriptional diversity of HNSCC. Recognition of human papillomavirus (HPV) involvement in HNSCC carcinogenesis has resulted in the categorization of two HNSCC subtypes (HPV-driven and HPV-negative) with distinct etiologies, molecular properties, clinical features, and prognostic outcomes. Differences in the molecular landscapes of HPV-driven and HPV-negative HNSCC occur genome-wide and encompass changes in genomic, epigenetic, and transcriptional landscapes. Even within each subtype, HNSCC tumors have substantial inter-tumor and intra-tumor molecular heterogeneity. Improving the understanding of the underlying biological function of these complex molecular landscapes through emerging cross-platform genomic analyses is essential to developing more effective diagnostic and therapeutic strategies for HNSCC.