TP63 and head and neck squamous cell carcinoma: To address this shortcoming, we leveraged genomic, transcriptomic, and epigenomic data from HPV+ HNSCC tumors and preclinical cell line models and identified p63 as a critical regulator that affects multiple facets of HPV+ HNSCC biology, including pathways essential in HPV-mediated carcinogenesis, and HNSCC subtype-specific gene expression.