Remarkably, HER3 KD specifically reduced activation of AKT and mTOR (as judged by the accumulation of pAKT and pS6) but not ERK (pERK) in this and other PIK3CA wild type HNSCC cell lines, including HN12 and SCC47, the latter a representative HPV+ cellular systems22 (Fig. 2a and Supplementary Fig. 2). Here, PIK3CA is linked to head and neck squamous cell carcinoma.