HPV and the Immune System in Head and Neck Cancers: Therapeutic Considerations

Immunotherapy applications for head and neck squamous cell carcinoma (HNSCC) are rapidly evolving. The progress towards immunotherapy has demonstrated improved outcomes for patients with HNSCC. Human papillomavirus (HPV)-associated HNSCC has a much better prognosis and differs from HPV-negative HNSCC in its genomic and immunologic profile, with strikingly higher immune cell activation and infiltration. Despite an increased incidence of HPV-associated HNSCC, and differences in immune signature based on HPV status, the management does not differ from non-HPV tumors. Clinical trials are ongoing to integrate immunotherapy in the management of early- and late-stage HNSCC, and its current use is limited to the metastatic setting. This article describes the role of immune therapy in HPV-associated HNSCC along with the evidence and perspective behind differing therapeutic considerations.