Immunometabolic Alterations by HPV Infection: New Dimensions to Head and Neck Cancer Disparity

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer, with high morbidity and mortality. Racial disparity in HNSCC is observed between African Americans (AAs) and whites, effecting both overall and 5-year survival, with worse prognosis for AAs. In addition to socio-economic status and demographic factors, many epidemiological studies have also identified factors including coexisting human papillomavirus (HPV) infection, primary tumor location, and a variety of somatic mutations that contribute to the prognostic incongruities in HNSCC patients among AAs and whites. Recent research also suggests HPV-induced dysregulation of tumor metabolism and immune microenvironment as the major regulators of HNSCC patient prognosis. Outcomes of several preclinical and clinical studies on targeted therapeutics warrant the need to elucidate the inherent mechanistic and population-based disparities underlying patient responses. This review systematically reports the underlying reasons for inconsistency in disease prognosis and therapy responses among HNSCC patients from different racial populations. The focus of this review is twofold: aside from discussing the causes of racial disparity, we also seek to identify the consequences of such disparity in terms of HPV infection and its associated mutational, metabolic, and immune landscapes. Considering the clinical impact of differential patient outcomes among AA and white populations, understanding the underlying cause of this disparity may pave the way for novel precision therapy for HNSCC. REVIEW

Tumor microenvironment: an evil nexus promoting aggressive head and neck squamous cell carcinoma and avenue for targeted therapy

“… 85 In addition to the immunological differences between HPV +ve and HPV −ve tumors, recent studies have shown differential metabolic compartmentalization inside these tumors. 28 While HPV +ve -associated tumors display increased oxidative phosphorylation (OXPHOS) in the tumor core and higher rate of aerobic glycolysis, the inverse is true for HPV −ve tumors. 55 This differential metabolism is associated with increased centrally localized staining of glucose transporter-1 (GLUT1), lactate dehydrogenase-B (LDHB), monocarboxylase transporter 1 (MCT1), and cyclooxygenase 5B (COX5B) in HPV +ve tumors, but more peripheral staining along with the higher concentration of lactic acid in HPV −ve tumors.…”

NR2F6 as a Prognostic Biomarker in HNSCC

“…The clearest difference is seen in oropharyngeal cancers, in which the human papillomavirus (HPV) has a huge impact on the overall survival of patients. In the oral cavity, the hypopharynx, and the larynx, no impact on the overall survival by HPV has been detected so far [ 30 ]. Moreover, the response towards irradiation is also dependent on the site of origin.…”

Tumor microenvironment is not an ‘innocent bystander’ in the resistance to treatment of head and neck cancers (Review)

“…Currently, the tumor microenvironment is defined as a very complex ecosystem of cellular and non-cellular components, that are continuously evolving, characterized by unique features, that lead to immunosuppression and diminished anticancer immunity. The cellular components are represented by modified stromal cells (cancer-associated fibroblasts, endothelial cells, adipocytes, neuroendocrine cells, blood cells), and infiltrating immune cells (T cells, B cells, natural killer cells, dendritic cells, macrophages, and myeloid-derived suppressor cells) (25,30,31). The non-cellular components of the tumor microenvironment are proteins of the extracellular matrix (collagen, fibronectin, elastin, laminin, tenascin) that influence proliferation, invasion, metastases, and survival of the cancer cells.…”