RESUMEN
(1) Background: Head and neck cancer (HNC) ranks as the sixth most prevalent cancer in the world. In addition to the traditional risk factors such as alcohol and tobacco consumption, the implication of the human papillomavirus (HPV) is becoming increasingly significant, particularly in oropharyngeal cancer (OPC). (2) Methods: This study is based on a review analysis of different articles and repositories investigating the mutation profile of HPV-related OPC and its impact on patient outcomes. (3) Results: By compiling data from 38 datasets involving 8311 patients from 12 countries, we identified 330 genes that were further analyzed. These genes were enriched for regulation of the inflammatory response (RB1, JAK2, FANCA, CYLD, SYK, ABCC1, SYK, BCL6, CEBPA, SRC, BAP1, FOXP1, FGR, BCR, LRRK2, RICTOR, IGF1, and ATM), among other biological processes. Hierarchical cluster analysis showed the most relevant biological processes were linked with the regulation of mast cell cytokine production, neutrophil activation and degranulation, and leukocyte activation (FDR < 0.001; p-value < 0.05), suggesting that neutrophils may be involved in the development and progression of HPV-related OPC. (4) Conclusions: The neutrophil infiltration and HPV status emerge as a potential prognostic factor for OPC. HPV-infected HNC cells could potentially lead to a decrease in neutrophil infiltration. By gaining a better molecular understanding of HPV-mediated neutrophil immunosuppression activity, it is possible to identify a meaningful target to boost antitumor immune response in HNC and hence to improve the survival of patients with HNC.