Building on our previous work (LaFranzo et al. 2020; Schillebeeckx et al. 2020, 2022), we developed an RNA-sequencing-based classifier called OncoPrism®-HNSCC to predict disease control with increased sensitivity and specificity compared to PD-L1 IHC in patients with RM-HNSCC treated with anti-PD-1 monotherapy. This evidence concerns the gene CD274 and head and neck squamous cell carcinoma.