Link between multiple human papillomavirus 16 and 18 infection and prostate cancer, and relevance of tumor characteristics.

It has been demonstrated that there is an association between human papillomavirus (HPV) infection and prostate cancer (PCa). However, HPV infection in PCa and the causal role remains unclear, therefore the objective of the present study was to confirm this association and evaluate the clinical tumor characteristics to understand the underlying molecular mechanisms. HPV detection and genotyping were analyzed in 117 paraffin-embedded prostate tissue from men diagnosed by histological analysis with adenocarcinoma, and a group including 60 men with benign prostatic hyperplasia (BPH). The clinical and histological characteristics in tissues with PCa were evaluated, comparing HPV-infected vs. not infected, single vs. multiple HPV infection, and low-risk (LR) HPV vs. high-risk-HPV (HR-HPV). In 84.1% of all samples, HPV was detected, exhibiting a higher prevalence in tissues with PCa (109/117 or 93%) compared with tissues with BPH (40/60 or 67%), as evidenced by the association between the infection and PCa [odds ratio (OR); 6.8; 95% confidence interval (CI), 2.77-16.69; P<0.0001]. The main viral genotypes detected in order of decreasing prevalence were 16, 11, 18 and 6. Detection of multiple HPV infection was significantly higher in PCa (78/117 or 66.7%) than in HPB (21/60 or 35%) (OR, 3.7; 95% CI, 1.929-7.151; P=0.0001). Of note, co-infections containing interactions of HPV 16-18 types were associated with PCa (OR, 3.9079; CI, 1.2867-11.8685; P=0.0162) which indicates new epidemiological data in PCa. Cribriform cells, prostatic atrophy and prostatitis were statistically less frequent in tissues with PCa HPV-infected vs. not infected (P<0.05). Cribriform cells were also more frequent in single vs. multiple HPV infection (P<0.05), and in tissues with LR-HPV vs. HR-HPV (P<0.05). A worse prognosis was observed for HPV-not infected, with a single HPV infection and LR-HPV infection, suggesting that tumor progression could be attributed to the resistance of human PCa cells to tumor apoptosis in the presence of multiple HPV types to ensure cell survival. Studies evaluating differences in the tumor microenvironment are needed to clarify the association between viral infections and histopathological tumor characteristics.