Relationship Between Infection Of Human Papillomavirus And Risk Of Bladder Cancer

According to data from China Cancer Registration between 1988-2002,the incidence of bladder cancer showed increasing trend year by year and ranked the first among the tumors of male reproductive system and urinary tract. Transitional cell carcinoma (TCC) is the most common bladder cancer, accounting for 90% among all bladder cancer. However, the etiology and pathogenesis of bladder carcinoma have not yet entirely clear until now. Human papillomavirus (HPV) has been now proved to be a necessary cause of cervical cancer, which made cervical cancer as the first cancer that can be prevented, early detected and cured. In view of the bladder and cervix have similarities, such as epithelial cells in part as component and the same semi-exposed organs of the body, and the exciting possibility of retrograde infection some researchers have proposed HPV infection, especially high-risk types, may also be involved in the occurrence of bladder cancer.Objective To investigate the high-risk HPV infection and risk of bladder cancer among men, and explore the correlation with the clinical analysis of the relationship between tumor grading and staging. Furthermore, due to relatively a few studies on HPV infection and bladder cancer all over the world, and differences in sample sizes, detection methods and various virus sub-types detected in these published article, the findings about risk of HPV and bladder are still inconsistent and even contradictory. Therefore, the second aim of the current study was to collate all published information on HPV prevalence in bladder cancer and explore the association. It is hoped that such a systematic analysis of the results may afford new conclusions to help direct future researches.Methods Firstly, a hospital-based case-control study was designed. Total of 56 cases of male bladder transitional cell carcinoma and 21 healthy control matched by age frequently was enrolled in our study. Hybrid-captured 2 was used to detect 13 high-risk types of HPV. Between-group difference test was performed by using the chi-square test, and the heterogeneity was considered significant for P<0.05.Medline was employed to search for citations published from January 1989 to February 2010 using the MeSH terms "human","Pappilomavirus" and "bladder cancer". Additional relevant references cited in retrieved articles were also evaluated. Included studies had to meet the following criteria: (1) case-control study was included;(2) all kinds of histological types of bladder carcinoma were included;(3) If data or data subsets were published in more than one article, only the publication with the largest sample size was included. Fix-effect model and random-effect model, based on Mantel–Haenszel method and DerSimonian and Laird method, respectively, were used to pool the data. These two models provide similar results when between-studies heterogeneity is absent; otherwise, random-effect model is more appropriate. Between-group heterogeneity test was performed by using the x2-based Q test, and the heterogeneity was considered significant for P<0.05. Publication bias was evaluated with the funnel plot and the linear regression asymmetry test by Egger et al. A significance level of 0.05 was used as an indication for the presence of potential publication bias. All analyses were performed using the STATA 11.0 software.Results The prevalence of HPV were 62.5% and 4.8% in male TCC patients and healthy controls respectively. The prevalence of HPV was significantly higher in cases than in control (x2=20.45, P<0.001). Furthermore, the HPV prevalence was higher among patients with high differentiation than low differentiation (x2=9.91, P=0.007), as did in patients with earlier clinical stages than later clinical stages (x2=4.43, P=0.035).Sixteen studies met our inclusion criteria, including 13 reports based on DNA detected by PCR, 3 reports based on DNA detected not by PCR and 4 reports based on antigen and antibody. Firstly of all, data based on DNA detected either by PCR or not was analyzed, which in the heterogeneity test showed Q=23.48, P= 0.075.Thus Fix-effect model was used to evaluate the OR. Pooled OR estimation based on Meantel-Haenszel showed a value of 5.64 (95%CI=3.52-9.04), indicating a clear association between bladder cancer and HPV exposure. Egger's test, which was designed to indicate publication bias, proved to be insignificant t=-1.12, P=0.280. Secondly, data based on DNA detected only by PCR was analyzed, which in the heterogeneity test showed Q=14.13, P= 0.292. Thus Fix-effect model was used to evaluate the OR. Pooled OR estimation based on Meantel-Haenszel showed a value of 7.38 (95%CI=4.41-12.33), indicating a more clear association between bladder cancer and HPV exposure. Egger's test, which was designed to indicate publication bias, proved to be insignificant t=-0.24, P=0.814. Thirdly, data based on DNA detected not by PCR was analyzed, which in the heterogeneity test showed Q=3.72, P= 0.155. Thus Fix-effect model was used to evaluate the OR. Pooled OR estimation based on Meantel-Haenszel showed a value of 0.70 (95%CI=0.19-2.62), indicating no association between bladder cancer and HPV exposure. Egger's test, which was designed to indicate publication bias, proved to be insignificant t=0.58, P=0.666. Finally, data based on antigen and antibody detected was analyzed, which in the heterogeneity test showed Q=0.82, P= 0.844. Thus Fix-effect model was used to evaluate the OR. Pooled OR estimation based on Meantel-Haenszel showed a value of 5.89 (95%CI=3.35-10.35), indicating no association between bladder cancer and HPV exposure. Egger's test, which was designed to indicate publication bias, proved to be insignificant t=2.28, P=0.150.Conclusions Infection of high-risk types of HPV may be one of the risk factor for TCC in male, which play more roles in the early development of TCC in male. In addition, systematic review and meta analysis also prove the clear association between HPV infection and risk of bladder cancer. HPV infection could be one of effective biomarkers for screening of the high-risk population and early detection and treatment of bladder cancer probably.