The tumor immune microenvironments of HPV+ and HPV- head and neck cancers.

Human papillomaviruses (HPVs) are the etiological agent of a significant, and increasing, fraction of head and neck squamous cell carcinomas (HNSCC)-a heterogenous group of malignancies in the head and neck region. HPV infection accounts for approximately 25% of all cases, with the remainder typically caused by smoking and excessive alcohol consumption. These distinct etiologies lead to profound clinical and immunological differences between HPV-positive (HPV⁺ ) and HPV-negative (HPV^- ) HNSCC, likely related to the expression of exogenous viral antigens in the HPV⁺ subtype. Specifically, HPV⁺ HNSCC patients generally exhibit better treatment response compared to those with HPV^- disease, leading to a more favorable prognosis, with lower recurrence rate, and longer overall survival time. Importantly, a plethora of studies have illustrated that the tumor immune microenvironment (TIME) of HPV⁺ HNSCC has a strikingly distinct immune composition to that of its HPV^- counterpart. The HPV⁺ TIME is characterized as being immunologically "hot," with more immune infiltration, higher levels of T-cell activation, and higher levels of immunoregulation compared to the more immunologically "cold" HPV^- TIME. In general, cancers with an immune "hot" TIME exhibit better treatment response and superior clinical outcomes in comparison to their immune "cold" counterparts. Indeed, this phenomenon has also been observed in HPV⁺ HNSCC patients, highlighting the critical role of the TIME in influencing prognosis, and further validating the use of cancer therapies that capitalize on the mobilization and/or modulation of the TIME. This article is categorized under: Cancer > Molecular and Cellular Physiology Infectious Diseases > Molecular and Cellular Physiology.