Despite the strong number of alterations in HNSCC, the high expression of TP63 alone and the high expression of PHGDH, PSAT1, PSPH and MTHFD2 (four-genes signature) are not sufficient to impact on HNSCC patients’ overall survival, but the high expression of TP63, PHGDH, PSAT1, PSPH and MTHFD2 (five-genes signatures) seems to be more impacting on patients’ overall survival (Fig. 4a–c). The gene discussed is TP63; the disease is head and neck squamous cell carcinoma.