(A) Frequency of genomic alterations in genes involved in PI3K/Akt/mTOR signaling in the HNSCC TCGA dataset (n = 504), including HPV-positive (n = 95) and negative (n = 409) lesions. (B) Comparison of overall survival between patients with and without copy number loss of tumor suppressor genes (TSGs) in either PTEN, TSC1, TSC2, STK11, or EIF4E-BP1. (C) Isogenic cell panels of HNSCC cell lines, CAL27 and HN12, parental controls and with gene knockout in PTEN, TSC2, STK11, or EIF4E-BP1, as indicated.