In addition, GSEA revealed a significantly upregulated ‘natural killer cell mediated cytotoxicity’ pathway (enrichment score = 0.5990, adjusted p-value = 2e-04) in HPV − HNSCC cases but not in HPV + HNSCC cases (Fig. 3D and Supplementary Table S7 and Table S8), suggesting that IL6 may play an important role in the regulation of NK cell-mediated tumor immunity in the microenvironment of HPV − tumors. Here, IL6 is linked to neoplasm.