PIK3CA is the most frequently mutated gene in HPV-positive cancers, with frequencies ranging from 6 to 42% in cervical squamous cell carcinoma, 10–42% in cervical adenocarcinoma, and 22–56% in HPV-positive head and neck cancers [2,18,35,36,37,60,61,62,63,64,65,66,67,68,69]. The gene discussed is PIK3CA; the disease is head and neck cancer.