Recent studies have suggested that immune cells as part of tumor's microenvironment could partly explain the better outcome in HPV-associated oropharyngeal carcinoma. We performed a systematic review of the literature focused on differences in immune-infiltrate in HPV+ versus HPV- oropharyngeal cancers. This comprehensive search yielded 4308 original papers, of which 20 satisfied our eligibility criteria. Increase in both circulating and tumor infiltrating CD8+ lymphocytes is mainly seen in HPV+ oropharyngeal carcinoma. Interestingly, the survival benefit associated with increase in immune cells is equal both in HPV+ and HPV- oropharyngeal cancer. Based on these results, our review underscores the role of the immune system in the biological and clinical behavior of oropharyngeal squamous cell carcinomas (OPSCC) and might open doors to further investigate immune modulatory treatment options in OPSCC patients.
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