In the phase III CheckMate 651 trial, first-line nivolumab plus ipilimumab did not improve overall survival compared with the EXTREME regimen in patients with recurrent or metastatic SCCHN, yielding a median OS of 13.9 versus 13.5 months in the intent-to-treat population (HR 0.95, p = 0.495) and 17.6 versus 14.6 months in those with PD-L1 CPS ≥ 20 (HR 0.78, p = 0.047), despite a substantially lower rate of grade 3–4 treatment-related adverse events (28.2% vs. 70.7%). Here, CD274 is linked to head and neck squamous cell carcinoma.