Since different NOTCH1 expression levels were detected in p16-positive and -negative HNSCC patients and high NOTCH1 expression was only a positive prognostic factor in p16-positive patients, NOTCH1 signaling was analyzed in three HPV-positive and nine HPV-negative HNSCC cell lines. The gene discussed is CDKN2A; the disease is head and neck squamous cell carcinoma.