To decide the neighbor genes’ biological interaction network of these 20 stemness-related genes in HNSCC, we identified the top 10 frequent alterations were PIK3CA, FGF3, FGF19, FGF4, DVL3, P3H2, GNB4, COL22A1, COL14A1 and PLOD2. Phosphoinositide 3-kinase (PI3 K) and serine/threonine kinase AKT pathway regulate cellular functions such as proliferation, cell survival, and differentiation (Engelman et al., 2006). This evidence concerns the gene PLOD2 and head and neck squamous cell carcinoma.