HPV+ HNSCC subtypes also have differences in copy number alteration (CNA) patterns and mutation frequencies, specifically in PIK3CA. Furthermore, HPV E6 and E7 oncoproteins are implicated in regulating the PI3K/AKT/mTOR network in cancer cells under both normoxic and hypoxic conditions, specifically by regulating AKT, a main effector of both PI3K and mTORC1 signaling (71). This evidence concerns the gene PIK3CA and cancer.