This prompted us to perform a thorough analysis of PI3K/AKT/mTOR pathway components to investigate the mutational status of PIK3CA and AKT1 genes and the immunohistochemical expression of a number of pathway-related proteins (EGFR, PDK1, p-AKT, PTEN, p-S6) using a consecutive series of 93 surgically treated HNSCC patients, and to establish correlations with the clinicopathological parameters and disease outcome. Here, RPS6 is linked to head and neck squamous cell carcinoma.