Abstract
Simple SummaryHead 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.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.
Highlights
Head and neck squamous cell carcinomas (HNSCC) are the seventh most common cancers worldwide, with approximately 890,000 new cases and mortality of 450,000 reported in 2018 [1]
The presence of human papillomavirus (HPV) in HNSCC varies with the anatomical site; that is to say, it has been found in 48.5% of oropharynx squamous cancers (OPSCC), 24% of cancers of the oral cavity (OCSCC), and 22% of those in the larynx (LASCC) [9]
The results indicated that high expression of KLF10, APBB2, ACTN1, AREG, MT2A, PTPN12, and PTHLH was associated with low survival in HPV−unrelated HNSCC (Figure 5A–G), whereas high expression of SLC25A39 and GJB2 was associated with poor survival only in HPV+ HNSCC (Figure 5H,I)
Summary
Head and neck squamous cell carcinomas (HNSCC) are the seventh most common cancers worldwide, with approximately 890,000 new cases and mortality of 450,000 reported in 2018 [1]. Increasing evidence has shown that HNSCC associated with HPV has a better prognosis, especially in oropharynx squamous cancers (OPSCC) [7,8]. An increase in HNSCC associated with HPV and decrease in cases related to smoking have been documented both in Europe and North America [7]. The presence of HPV in HNSCC varies with the anatomical site; that is to say, it has been found in 48.5% of OPSCC, 24% of cancers of the oral cavity (OCSCC), and 22% of those in the larynx (LASCC) [9]. The most frequent viral genotype in HNSCC is HPV16, followed by HPV 18, 33, 35, 52, 45, and 39 [10]
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