PIK3CA and esophageal squamous cell carcinoma: In broad terms, HPV negative tumors were similar to lung and esophageal squamous cell carcinomas with respect to mutational profiles, characterized by activating alterations of receptors tyrosine kinase (RTKs)-RAS-PI3K pathways, as well as mutational inactivation of TP53 and CDKN2A. In contrast, HPV positive tumors were characterized by activating alterations of PIK3CA, FGFR3, and E2F1 along with inactivation of TP53 and RB1 by the viral oncoproteins E6 and E7 respectively [12,13].