Furthermore, the phase III CheckMate 651 trial of the anti-PD-1 mAb nivolumab and the anti-CTLA-4 mAb ipilimumab for R/M HNSCC showed no significant survival benefit versus standard of care treatment, although there was a trend of OS benefit in patients with high PD-L1 expression.21 This evidence concerns the gene CTLA4 and head and neck squamous cell carcinoma.