The interplay between HPV and host immunity in head and neck squamous cell carcinoma

Persistent infection with human papillomavirus (HPV) type 16 is a major risk factor for the development of head and neck squamous cell carcinoma (HNSCC), in particular oropharyngeal squamous cell carcinoma (OPSCC). The oropharyngeal epithelium differs from the mucosal epithelium at other commonly HPV16-infected sites (i.e., cervix and anogenital region) in that it is juxtaposed with the underlying lymphatic tissue, serving a key immunologic function in the surveillance of inhaled and ingested pathogens. Therefore, the natural history of infection and immune response to HPV at this site may differ from that at other anatomic locations. This review summarizes the literature concerning the adaptive immune response against HPV in the context of HNSCC, with a focus on the T-cell response. Recent studies have shown that a broad repertoire of tumor-infiltrating HPV-specific T-cells are found in nearly all patients with HPV-positive tumors. A systemic response is found in only a proportion of these. Furthermore, the local response is more frequent in OPSCC patients than in cervical cancer patients and HPV-negative OPSCC patients. Despite this, tumor persistence may be facilitated by abnormalities in antigen processing, a skewed T-helper cell response, and an increased local prevalence of T-regulatory cells. Nonetheless, the immunologic profile of HPV-positive vs. HPV-negative HNSCC is associated with a significantly better outcome, and the HPV-specific immune response is suggested to play a role in the significantly better response to therapy of HPV-positive patients. Immunoprofiling may prove a valuable prognostic tool, and immunotherapy trials targeting HPV are underway, providing hope for decreasing treatment-related toxicity.