High SPI predicted a shorter overall survival (OS) in HNSCC patients, in the meantime, also demonstrated a lower CD8+ T cell infiltration and a higher enrichment of macrophages and fibroblasts than the low-SPI group, focusing on several up-regulated pathways such as epithelial mesenchymal transition (EMT), MYC targets v1, E2F targets, mTORC1 signaling, hypoxia, MYC targets v2, angiogenesis, G2M checkpoint, and glycolysis. The gene discussed is MYC; the disease is head and neck squamous cell carcinoma.