Even if HPV-driven HNSCC tumors are postulated to have an “active immune response” in general (81) and to promote an inflammatory environment by co-activation of classic and alternative NF-κB pathways (82), two distinct HPV-driven HNSCC subtypes have been defined based on gene expression-based consensus clustering that might explain the significant heterogeneity in clinical behavior in HPV-driven HNSCC (83, 84). Here, NFKB1 is linked to head and neck squamous cell carcinoma.