Human papillomavirus-stratified analysis of the prognostic role of miR-21 in oral cavity and oropharyngeal squamous cell carcinoma

Human papillomavirus (HPV) infection plays a significant role in the development and progression of head and neck squamous cell carcinoma (HNSCC). Expression of miR-21 has a prognostic role in a wide variety of cancers. The upregulation of miR-21 suppresses a number of target genes, including phosphatase tensin homologue (PTEN) and programmed cell death 4 (PDCD4). We investigated the association between the expression of miR-21 and the clinical features of HNSCC using stratified analysis based on HPV infection status. HPV status and miR-21 expression in HNSCC tissues from 167 patients were evaluated using in situ hybridization. The expression of PDCD4 and PTEN was examined by immunohistochemistry. The up-regulation of stromal miR-21 expression occurred in 40.6% of HPV-negative samples and 28.3% of the HPV-positive group. In HPV-stratified multivariate analysis, high miR-21 expression was associated with poor cancer-specific survival in HPV-negative tumors, but not in HPV-positive tumors. There was a significant association between miR-21 and cytoplasmic PDCD4 overexpression in HPV-negative HNSCCs. We suggest that stromal miR-21 expression is an independent prognostic factor in HPV-negative tumors and miR-21 may play different roles depending on HPV infection status.