In 2016, the results of two milestone trials ]KEYNOTE-012 (21, 22) and CheckMate 141 (23)] promoted the antagonists of PD-1 / PD-L1 axis such as pembrolizumab (MK-3475) and nivolumab (BMS-936558) which become the earliest targeted therapeutic drugs for HNSCC approved by the US Food and Drug Administration (FDA). This evidence concerns the gene CD274 and head and neck squamous cell carcinoma.