Super-enhancer analysis identified candidate SE-target genes, including MYL4, CMYA5, and TNNT3, linked to PNI-associated biology.<h4>Conclusions</h4>PNI in HNSCC is associated with coordinated extracellular-matrix, neuroimmune, and immune-suppressive remodeling. The gene discussed is CMYA5; the disease is head and neck squamous cell carcinoma.