Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous group of tumors that originate in the lip/oral cavity, hypopharynx, oropharynx, nasopharynx, and larynx. An estimated 66,630 new cases are diagnosed in the United States annually, and 14,620 people die of the disease (Siegel et al, 2021). Historically, HNSCC has been associated with tobacco and alcohol use; however, infection with high-risk human papillomavirus (HPV) is now recognized as a causative factor for a growing subset of tumors (NCCN, 2020; Chaturvedi et al, 2011). Human papillomavirus–associated oropharyngeal carcinoma is a distinct entity in terms of etiology, biology, and clinical behavior; importantly, it has a more favorable prognosis and might require less intensive therapy. Despite advances and innovations in multimodality treatment and improved understanding of head and neck carcinogenesis, death rates are increasing for cancers of the oral cavity and pharynx overall (0.5% increase per year from 2009 to 2018), and the prognosis for recurrent/metastatic HNSCC remains poor (Siegel et al, 2021; Chang et al, 2017; Pisani et al, 2020).