As E6 and E7 function through cell cycle dysregulation by eliminating RB1 and TP53, very few alterations in additional cell cycle regulators occur in HPV+ disease: inactivation of CDKN2A, or TP53, or overexpression of CDK6 or CCND1, occur seldom in HPV+ HNSCC. Here, RB1 is linked to head and neck squamous cell carcinoma.