When comparing PD-1/PD-L1 expression in HNSCC versus other epithelial cancers, one unique feature is its association with human papillomavirus (HPV), which has been shown to be the driver of carcinogenesis in 40–80% of oropharyngeal carcinomas, but not in malignancies arising from the oral cavity or other head and neck sites [10]. This evidence concerns the gene CD274 and head and neck squamous cell carcinoma.