TP53 and head and neck squamous cell carcinoma: Both p53 and RB pathway mutations contribute to the unrestricted replication of HNSCC cells.100 In HPV+ neoplasms, the degradation of pRb by E7 contributes to the secretion of E2F and unregulated HNSCC cell proliferation.163 In persistent HPV infection, E2-regulated expression of E6 and E7 is responsible for p53 degradation and Rb functional suppression.150 When pRb is dysregulated, oral epithelial dysplasia has an increased likelihood of transforming into malignant carcinomas.164