Some analysts suggest HPV-positive tumors (which often have an inflamed microenvironment) respond somewhat better, but differences are not dramatic.[57,58] Tumor mutational burden (TMB) is another biomarker of interest: a small fraction of HNSCC has high TMB, and these may respond well to PD-1 blockade (pembrolizumab has tissue-agnostic approval for TMB ≥ 10).[59] Gene expression profiles indicating T-cell inflammation (interferon-γ signature) have also correlated with response in exploratory analyses. This evidence concerns the gene PDCD1 and head and neck squamous cell carcinoma.