An
HPV infection is involved in the etiology of about 25 % of
head and neck squamous cell carcinomas (
HNSCC). It has been postulated that a strong antitumoral immune response in HPV-positive
tumors represents an important underlying mechanism for their good response to
therapy. Recently, the Warburg phenomenon has returned to the center of attention because it affects antitumoral immune response and response to
therapy. Accumulation of
tumor cell-derived
lactate inhibits cytotoxic T cells, as these, analogous to
cancer cells, depend on glycolysis and
lactate secretion for fulfillment of energy needs. Sparse information exists on the Warburg effect in
HNSCC. This study aimed to characterize the metabolic and immunological features of HPV-negative and HPV-positive
HNSCC. An immunohistochemical analysis of oropharyngeal
carcinomas showed an enhanced antitumoral immune response (CD8/CD4 ratio) together with increased levels of
proteins involved in transmembranous metabolite transportation (GLUT1 and CD147) and respiratory metabolism (COX5B) in HPV-positive
tumors as compared to HPV-negative
tumors.
mRNA and Western blot analyses of an HPV-positive and HPV-negative
HNSCC cell line revealed metabolic characteristics similar to the in vivo situation. Additionally, the HPV-negative cell line showed stronger extracellular
lactate accumulation. In contrast, the HPV-positive cell line presented with better adaption to
lactic acidosis suggesting an ability to metabolize
lactate. Our results indicate that HPV-positive and HPV-negative
carcinomas do not only differ in terms of
tumor immune microenvironment, but also in terms of
tumor metabolism, characterized by an increased
glucose and respiratory metabolism together with decreased
lactate accumulation in HPV-positive
HNSCC. Therefore, targeting metabolic pathways could represent a promising adjunct in the
therapy of HPV-positive
HNSCC.