Contribution of HPV Status for Neutrophil Extracellular Traps Release in Oropharyngeal Cancer

Background: Oropharyngeal squamous cell carcinoma (OP-SCC) represents a public health problem and human papillomavirus (HPV) is one of the risk factors. Neutrophil extracellular traps (NET) are meshes of DNA strands and granule proteins. NET has been identified in diverse cancers, whether associated with viruses or not. However, there is no information on NET in OP-SCC. We aimed to evaluate the NET release by neutrophils in the OP-SCC microenvironment, stratified by HPV status.

Methods: This cross-sectional study analyzed OP-SCC biopsy specimens diagnosed from 1997 to 2021. HPV status was determined by p16 immunohistochemistry and "in situ" hybridization. Neutrophils were detected by CD66b immunohistochemistry. Immunofluorescence was used to identify NET by co-localization of myeloperoxidase (MPO) and citrullinated histone H3 (H3Cit). Bivariate statistics, Kaplan-Meier survival analysis, and the log-rank test were performed.

Results: HPV-positive and HPV-negative OP-SCC had similar CD66b + neutrophil infiltration (p > 0.05), but the release of NET was significantly increased in HPV-positive compared to HPV-negative OP-SCC samples (p < 0.05). Overall survival was not impacted by NET indexes (p > 0.05).

Conclusion: The presence of HPV may stimulate NET release in the OP-SCC microenvironment.