The ORR of HPV positive HNSCC patients was significantly higher than that of HPV negative HNSCC patients (OR = 1.77; 95%CI = 1.14-2.74; <i>P</i> = 0.01), and this favorable effect occurred in pooled anti-PD-L1 trials (OR = 2.66; 95%CI = 1.16-6.11; <i>P</i> = 0.02). This evidence concerns the gene CD274 and head and neck squamous cell carcinoma.