These observations regarding an additional transforming activity of HPV E7, the ability of E7 to inactivate PTPN14, and the relative paucity of mutations in the Hippo pathway in HPV-positive HNSCC led us to hypothesize that HPV E7-mediated activation of YAP1 is required for the transforming activity of high-risk HPV E7. Here, PTPN14 is linked to head and neck squamous cell carcinoma.