The three mitogenic pathways most differentially altered with high mutation rates in HPV-negative and low mutation rates in HPV-positive head and neck squamous cell carcinoma (HNSCC) are p53 (targeted by E6), cell cycle/RB1 (targeted by E7), and Hippo/YAP1 (64, 65). Here, RB1 is linked to head and neck squamous cell carcinoma.