Prognostic Significance of the Microenvironment in Human Papillomavirus Oropharyngeal Carcinoma: A Systematic Review

Abstract

ObjectiveThe immune microenvironment of HPV‐associated (HPV+) oropharyngeal squamous cell carcinomas (OPSCCs) (HPV+OPSCCs) differs from that of HPV‐independent oropharyngeal cancers (HPV‐independent OPSCCs). The literature on the subject is very abundant, demanding an organized synthesis of this wealth of information to evaluate the hypothesis associating the favorable prognosis of HPV+OPSCC patients with a different immune microenvironment. A systematic review of the literature was conducted regarding the microenvironment of HPV+OPSCCs.Data SourceMEDLINE/PubMed, Embase, and Cochrane Library databases.Review MethodsA literature search was performed following PRISMA guidelines (Moher D. PLoS Med. 2009). The PEO (Population, Exposure, and Outcome) framework is detailed as follows: P: patients with oropharyngeal squamous cell carcinomas, E: human papillomavirus (HPV), and O: histological and immunological composition of the tumoral microenvironment (TME). No meta‐analysis was performed.ResultsFrom 1,202 studies that were screened, 58 studies were included (n = 6,474 patients; n = 3,581 (55%) HPV+OPSCCs and n = 2,861(45%) HPV‐independent OPSCCs). The presence of tumor‐infiltrating lymphocytes (TIL), CD3+ in 1,733 patients, CD4+ in 520 patients, and CD8+ (cytotoxic T lymphocytes (CTL)) in 3,104 patients, and high levels of PD‐L1 expression in 1,222 patients is strongly correlated with an improved clinical outcome in HPV+OPSCCs.ConclusionThis systematic review provides the most comprehensive information on the immune microenvironment of HPV+OPSCCs to date. Tumor‐infiltrating lymphocytes and PD‐L1 expression are associated with a favorable prognosis. B, CD8+ and resident memory cells densities are higher in HPV+OPSCCs. The importance of myeloid lineages is still a matter of debate and research.Level of EvidenceN/A Laryngoscope, 2023

Human Papilloma Virus Positive Oropharyngeal Squamous Cell Carcinoma and the Immune System: Pathogenesis, Immunotherapy and Future Perspectives

“…The TME immune profile of HPV + OPSCC vs. HPV − PSCC has also been correlated with prognosis, which may explain improved overall survival (OS) and disease-free survival (DFS) in HPV + OPSCC [ 18 , 19 , 134 , 135 ]. High-density TIL infiltrate, especially involving CD4 + , CD8 + , and CD3 + subsets, has been associated with greater OS rates in HPV + OPSCC [ 136 , 137 , 138 , 139 , 140 ]. Higher levels of infiltrating CD20 + B cells also correlates with improved prognosis, specifically those expressing FCER2 which were localised to the stroma in HPV + HNSCC tumours [ 141 , 142 ].…”

Exploring the role of HPV: from Sexually transmitted infection to Oropharyngeal Cancers

“…There is also impaired tumor infiltrating T cell recognition of antigens, cytokine secretion and activation of CD8+ cytotoxic T lymphocytes (CTLs), a T cell subset efficient in anti-tumor responses. It has been observed that HPVpositive HNC and OPC had a significantly higher tumor infiltrating CD4 + , CD8 + , and CD3 + subsets and chemokine response [118,119]. HPV positive OPC are one of the most highly immune-cell infiltrated tumors that includes -CD3 + T cells, CD8 + T cells, Treg cells, B cells, and plasma cells, in comparison to HPV-OPC [120].…”