Among the p16-positive high-grade squamous cell carcinomas (n = 7), 4 with a relatively high labeling index of p16 (index, 80, 43, 41, and 38%) demonstrated no Rb1 protein expression (index, all 0%) and presented features related to aggressive biological behavior: tumor size ≥ 50 mm, lymph node involvement, and a high TNM stage (III/IV). The gene discussed is CDKN2A; the disease is neoplasm.