In spite of significant improvements, including the introduction of targeted and immunotherapies (most prominently, immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) [12]), as of 2015 the relative 5-year survival rate is only approximately 25–40 % for HPV- and 70–80 % for HPV+ HNSCC [1, 13, 14]. Here, CTLA4 is linked to head and neck squamous cell carcinoma.