Abstract & Commentary

Bladder Cancer Associated with HPV Infection

By Joseph F. John, Jr., MD, Associate Chief of Staff for Education, Ralph H. Johnson Veterans Administration Medical Center; Professor of Medicine, Medical University of South Carolina, Charleston, is Co-Editor for Infectious Disease Alert.

Dr. John reports no financial relationship to this field of study.

Synopsis: A large new meta-analysis reveals an association between infection of bladder tissue with human papilloma virus (HPV) and evolving bladder cancer. Future trends may include screening of men for infection with bladder-associated genotypes.

Sources: Li N, et al. Human papillomavirus infection and bladder cancer risk: A meta-analysis. J Infect Dis 2011;204:217-223.

The association of HPV infection and bladder cancer has been a topic of discussion for the last decade, but has not surfaced because of important other outcomes of HPV infection. HPV is increasing in its prevalence globally and its chronic nature raises many issues in and around the genital tract. We already know of the oncogenic nature of this virus and its genetic plasticity, so an association with bladder cancer would not be so surprising.

An earlier meta-analysis was been published in 2007,1 but several questions remained unanswered. Thus, this new meta-analysis from Beijing and Yale now includes 52 publications, making for a robust meta-analysis. Li et al found 2,855 cases of bladder cancer, most of which occurred in Europe. The prevalence of HPV averaged nearly 17%. HPV prevalence was higher when fresh HPV DNA was isolated from the bladder tissue in question. There are high-risk types of HPV seen in bladder cancer and stratification in this analysis found that clades A9, A7, and A10 were the most common. The five most common types were HPV-16, 18, 33, 6, and 31. The meta-analysis of 17 of 19 controlled studies revealed an odds ratio of 2.84 (confidence interval, 1.39-5.80). PCR detection of HPV DNA seemed to be the most sensitive way to demonstrate the association with HPV infection and the cancer.


Genital HPV infection may be associated with bladder cancer. Physicians seeing patients with HPV infection should be alerted to this association. Further studies are needed to determine the approach to this risk factor for bladder cancer. Since bladder cancer affects more men than women, there may be strategies that can mirror the effective use of Pap smears in women to detect HPV infection and even cervical neoplasia.

The authors of this study acknowledge that most of their analyses rested on tissue diagnosis of HPV, whereas a PCR test for HPV DNA will be more sensitive. One issue is whether urine would be a good reflection of bladder wall involvement with HPV as a precursor of bladder cancer. Many other scenarios can be advanced. Still, the major message of this article is fascinating and has been hanging out there for some time. Now we have this meta-analysis, which shows the relationship of HPV to bladder cancer. The next steps will be very exciting and of great benefit to those patients at greatest risk.


  1. de Sanjose S, et al. Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: A meta-analysis. Lancet Infect Dis 2007;7:453-459.