In contrast to HPV(−) HNSCC, HPV(+) tumors exhibit an enhanced response to radiation, and it has been hypothesized that this is at least partially due to retained function of p16 and perhaps the resulting impact on CDK4/6 signaling [10].The mechanisms by which active CDK4/6 promotes tumorigenesis and induces treatment resistance are not fully known (11). The gene discussed is CDK4; the disease is head and neck squamous cell carcinoma.