The tumor immune microenvironments of HPV⁺ and HPV⁻ head and neck cancers

Abstract

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 HPVpositive (HPV + ) and HPV-negative (HPV À ) 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 À 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 À 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 À 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.

Tumor Immune Microenvironment in Gynecologic Cancers

“…Unfortunately, the HPV-negative samples were too rare to correlate findings with survival in this group [136]. Other data are limited, but data from other disease sites such as oropharyngeal cancer support the concept of a cold TIME in HPV-negative cancers relative to HPV-positive counterparts [137,138].…”

Tumor Immune Microenvironment in Gynecologic Cancers

“…Unfortunately, the HPV-negative samples were too rare to correlate findings with survival in this group [136]. Other data are limited, but data from other disease sites such as oropharyngeal cancer support the concept of a cold TIME in HPV-negative cancers relative to HPV-positive counterparts [137,138].…”

Squamous cell carcinoma is associated with reduced IL34 expression, alterations in the Langerhans cell antigen‐processing‐presentation machinery and poor patient survival

“…Our recent work revealed that HPV+ HNSCC exhibits a heightened immune activity score, 24 and research has consistently shown that HPV+ HNSCC typically features a 'hot' tumor immune microenvironment, resulting in improved treatment responses and clinical outcomes. [44][45][46] Collectively, this suggests that IL34 may play a beneficial role in mucosal squamous epithelial cancers, and skin lesions associated with epithelial hyperplasia.…”

Optimizing Prognostic Assessment in High‐Risk Head and Neck Squamous Cell Carcinomas: The Impact of Tumor Budding and a Novel Histomorphological Scoring System

“…[37]. Potential explanations for such an increased incidence of TB in HPV‐negative cases may arise from distinct tumor microenvironmental characteristics and divergent immune responses between HPV‐negative and HPV‐positive tumors [46]. Additionally, observed differences in TB patterns may be attributable to distinct variations in the epithelial‐to‐mesenchymal transition (EMT) processes between HPV‐positive and HPV‐negative tumors [47].…”

Tumor Immune Microenvironment in Gynecologic Cancers

“…Unfortunately, the HPV-negative samples were too rare to correlate findings with survival in this group [136]. Other data are limited, but data from other disease sites such as oropharyngeal cancer support the concept of a cold TIME in HPV-negative cancers relative to HPV-positive counterparts [137,138].…”

Squamous cell carcinoma is associated with reduced IL34 expression, alterations in the Langerhans cell antigen‐processing‐presentation machinery and poor patient survival

“…Our recent work revealed that HPV+ HNSCC exhibits a heightened immune activity score, 24 and research has consistently shown that HPV+ HNSCC typically features a 'hot' tumor immune microenvironment, resulting in improved treatment responses and clinical outcomes. [44][45][46] Collectively, this suggests that IL34 may play a beneficial role in mucosal squamous epithelial cancers, and skin lesions associated with epithelial hyperplasia.…”

Optimizing Prognostic Assessment in High‐Risk Head and Neck Squamous Cell Carcinomas: The Impact of Tumor Budding and a Novel Histomorphological Scoring System

“…[37]. Potential explanations for such an increased incidence of TB in HPV‐negative cases may arise from distinct tumor microenvironmental characteristics and divergent immune responses between HPV‐negative and HPV‐positive tumors [46]. Additionally, observed differences in TB patterns may be attributable to distinct variations in the epithelial‐to‐mesenchymal transition (EMT) processes between HPV‐positive and HPV‐negative tumors [47].…”

Tumor Immune Microenvironment in Gynecologic Cancers

“…Unfortunately, the HPV-negative samples were too rare to correlate findings with survival in this group [136]. Other data are limited, but data from other disease sites such as oropharyngeal cancer support the concept of a cold TIME in HPV-negative cancers relative to HPV-positive counterparts [137,138].…”

Squamous cell carcinoma is associated with reduced IL34 expression, alterations in the Langerhans cell antigen‐processing‐presentation machinery and poor patient survival

“…Our recent work revealed that HPV+ HNSCC exhibits a heightened immune activity score, 24 and research has consistently shown that HPV+ HNSCC typically features a 'hot' tumor immune microenvironment, resulting in improved treatment responses and clinical outcomes. [44][45][46] Collectively, this suggests that IL34 may play a beneficial role in mucosal squamous epithelial cancers, and skin lesions associated with epithelial hyperplasia.…”

Optimizing Prognostic Assessment in High‐Risk Head and Neck Squamous Cell Carcinomas: The Impact of Tumor Budding and a Novel Histomorphological Scoring System

“…[37]. Potential explanations for such an increased incidence of TB in HPV‐negative cases may arise from distinct tumor microenvironmental characteristics and divergent immune responses between HPV‐negative and HPV‐positive tumors [46]. Additionally, observed differences in TB patterns may be attributable to distinct variations in the epithelial‐to‐mesenchymal transition (EMT) processes between HPV‐positive and HPV‐negative tumors [47].…”