| Summary: | <i>Background and objectives:</i> Laryngeal squamous cell carcinoma (LSCC) is one of the most common head and neck tumors. The molecular mechanism of LSCC remains unclear. The aim of this study was to evaluate the prevalence of Human papillomavirus (HPV) and single nucleotide polymorphisms (SNPs) of <i>TP53, MDM2, MDM4, MTHFR, CASP8,</i> and <i>CCR5</i> genes in LSCC, and to assess their correlations with patient survival. <i>Materials and Methods:</i> 49 LSCC patients were enrolled in this study. PCR and qRT-PCR were used to detect, identify, and quantify HPV. SNPs were genotyped using PCR and PCR-RFLP. <i>Results:</i> By analyzing the interactions of the SNPs of the genes with clinical parameters, the majority of patients with lymph node status (N1,2) were identified as carriers of <i>MDM2</i> <i>T/G</i>, <i>CASP8</i> <i>ins/del</i>, <i>CCR5</i> <i>wt/wt</i> SNP. Cluster analysis showed that patients with <i>MDM2</i> <i>T/T</i> SNP survive longer than patients identified as <i>CASP8</i> <i>ins/ins</i>, <i>MTHFR</i> <i>C/C,</i> and <i>MDM4</i> <i>A/A</i> variant carriers; meanwhile, LSCC patients with <i>MDM2</i> <i>T/T</i> polymorphic variant had the best survival. Multivariate analysis showed that HPV-positive patients without metastasis in regional lymph nodes (N0) and harboring <i>CASP8</i> <i>ins/del</i> variant had the best survival. Meanwhile, HPV-negative patients with identified metastasis in lymph nodes (N1 and N2) and <i>CASP8</i> <i>ins/del</i> variant had poor survival. <i>Conclusions:</i> This finding suggests patients survival prognosis and tumor behavior are different according HPV status, SNP variants, and clinical characteristics of the LSCC.
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