The PI3K/AKT/mTOR signaling pathway has emerged as one of the most frequently altered in multiple cancers including HNSCC [3–5] and multiple upstream and downstream components such as Epidermal Growth Factor Receptor (EGFR), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT/PKB), phosphatase and tensin homolog (PTEN) and mammalian target of rapamycin (mTOR) have been found deregulated, making this pathway very attractive for the development of molecular-targeted therapies [6]. Here, PIK3CA is linked to head and neck squamous cell carcinoma.