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

Objective The 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 Source MEDLINE/PubMed, Embase, and Cochrane Library databases. Review Methods A 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. Results From 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. Conclusion This 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 Evidence NA Laryngoscope , 134:1507–1516, 2024