PIK3CA is the most frequently mutated gene in HPV-positive HNSCC [102], resulting in the upregulation of PI3K signaling due to gain-of-function mutations in PIK3CA. Given the importance of PI3K signaling in HPV-positive HNSCC and the role of IQGAP1 in scaffolding PI3K signaling [48], we hypothesized that IQGAP1 also plays a role in HPV-positive HNSCC. The gene discussed is PIK3CA; the disease is head and neck squamous cell carcinoma.