LAUSR

Simple Summary Head and neck squamous cell carcinomas (HNSCC) are a heterogeneous group of neoplasms that show diverse clinical and biological characteristics associated with human papillomavirus (HPV). Biological and clinical characterization is essential to stratify patients based on prognostic and predictive factors. The biological features of HNSCC may change according to geography and population characteristics. Studies on the molecular biology of HNSCC in Mexico are scarce. In the present study, we analyzed 414 Mexican patients with HNSCC and determined the presence and genotype of HPV, p16 expression, and global gene expression profiles. Twenty-two percent of total cases were HPV+, and 32% were p16+. We identified genes associated with survival, such as SLIRP, KLF10, AREG, ACT1, and LIMA. In addition, CSF1R, MYC, and SRC genes were identified as potential therapeutic targets. This study offers information that may be relevant for our understanding of the biology of HNSCC and the development of therapeutic strategies. Abstract Head and neck squamous cell carcinomas (HNSCC) show a variety of biological and clinical characteristics that could depend on the association with the human papillomavirus (HPV). Biological and clinical characterization is essential to stratify patients based on prognostic and predictive factors. Reports on HNSCC are scarce in Mexico. Herein, we analyzed 414 Mexican patients with HNSCC, including oropharynx (OPSCC), larynx (LASCC), and oral cavity (OCSCC), and identified HPV DNA and p16 expression. Global gene expression profiles were analyzed in 25 HPV+/p16+ vs. HPV−/p16− cases. We found 32.3% p16+ and 22.3% HPV+ samples, HPV 16, 18, 39, 52, and 31 being the most frequent genotypes. For OPSCC, LASCC and OCSCC, 39.2, 14.7, and 9.6% were HPV+/p16+, respectively. High expression of SLIRP, KLF10, AREG, and LIMA was associated with poor survival; in contrast, high expression of MYB and SYCP2 correlated with better survival. In HPV+ cases, high expression of SLC25A39 and GJB2 was associated with poor survival. Likewise, EGFR, IL-1, IL-6, JAK-STAT, WNT, NOTCH, and ESR1 signaling pathways were downregulated in HPV+ cases. CSF1R, MYC, and SRC genes were identified as key hubs and therapeutic targets. Our study offers information regarding the molecular and clinical characteristics of HNSCC in Mexican patients.