A HPV16-related prognostic indicator for head and neck squamous cell carcinoma

Background: The human papillomavirus (HPV) is emerging as an important risk factor in head and neck squamous cell carcinoma (HNSCC) patients. This has been observed particularly in the case of HPV16. The HPV16+ HNSCC subtype has distinct pathological, clinical, molecular, and prognostic characteristics. This study aimed to identify potential microRNAs (miRNAs) and their roles in HPV16+ HNSCC progression. Method: miRNA, mRNA and the clinical data of 519 HNSCC and 44 HNSCC-negative samples were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed miRNAs (DEMs) in HPV16-related HNSCC tissues with prognostic value were selected. DEM levels were assessed based on clinicopathological parameters and overall survival (OS). Target genes were also predicted and functional analysis based on Gene Set Enrichment Analysis (GSEA) were then performed. Results: In HPV16+ HNSCC tissues, miR-99a-3p and miR-4746-5p were significantly upregulated. In contrast, miR-411-5p was shown to be downregulated. miR-99a-3p(high)miR-411-5p(low)miR-4746-5p(high) expression could estimate improved OS and low frequent perineural invasion (PNI). Predicted target genes were enriched in cell growth, neuroepithelial cell differentiation, MAPK and FoxO signaling pathways. Epithelial mesenchymal transition (EMT) gene set and invasion related genes were downregulated in miR99a-3p(high)miR-411-5p(low)miR-4746-5p(high) HNSCC patients. Conclusion: miR-99a-3p, miR-411-5p and miR-4746-5p might participate in HPV16+ HNSCC progression through EMT related pathways and affect prognosis.