For head and neck squamous cell carcinomas (HNSCCs) it has been shown by Henderson and colleagues that HPV+ compared to HPV− tumors have elevated APOBEC3B and that PIK3CA helical domain mutations are APOBEC-driven in multiple cancers, including HPV+ HNSCC [136]. The gene discussed is APOBEC3B; the disease is head and neck squamous cell carcinoma.