Such alterations include loss of the tumor suppressor PTEN and amplification of PIK3CA and Akt. One study found HPV-negative tumors expressed more activated EGFR than HPV-positive ones and this expression correlated with activated Akt, implicating EGFR as an upstream regulator of Akt signaling in penile cancer [46]. The gene discussed is EGFR; the disease is penile cancer.