Circumcision has been found to lower men’s risk of contracting HIV through heterosexual sex, and now new findings suggest that it also cuts the risk of infection with the human papillomavirus (HPV) in both HIV-positive and HIV-negative men.

The findings, from two studies in Uganda, suggest there may be additional benefits to offering circumcision to men in countries with high rates of heterosexual HIV transmission.

What the findings could mean for other countries, including the U.S., is less clear, researchers say.

In 2005 and 2006, three clinical trials in Uganda, South Africa and Kenya showed that circumcision can cut a man’s risk of HIV infection through heterosexual sex by up to 60 percent. Subsequent studies of those men also found a lower prevalence of HPV among those who were circumcised and HIV-negative.

But it hadn’t been clear whether that lower prevalence was specifically due to a lower risk of HPV infection. Nor has it been known whether circumcision affects HPV risk in HIV-positive men, according to Dr. Ronald H. Gray, a professor at Johns Hopkins University School of Public Health in Baltimore and the senior researcher on the Ugandan studies.

HPV is a highly common virus with more than 100 strains, some of which cause genital warts. While the immune system clears the infection in most people, persistent infection with certain HPV strains can lead to cancer. HPV is the primary cause of cervical cancer in women, and it can also lead to penile and anal cancers.

Gray noted that HPV-related cancers are a serious public health problem in sub-Saharan Africa - in contrast to developed countries, where, for example, women have access to regular Pap tests to detect cervical cancer early and, in recent years, HPV vaccination.

Moreover, people with HIV infection often have HPV infections as well, and are especially susceptible to developing HPV-related cancers, Gray said.

The current studies, published in the Journal of Infectious Diseases, found that circumcision appeared to lower the rate of infection with cancer-related HPVs in both HIV-negative and HIV-positive men - by 33 percent and 23 percent, respectively, compared with uncircumcised men.

The studies included 210 HIV-positive and 840 HIV-negative men between the ages of 15 and 49 who were randomly assigned to undergo immediate or delayed circumcision. At the outset, 39 percent of HIV-negative and roughly three-quarters of HIV-positive men carried at least one cancer-related strain of HPV.

Circumcision appeared to lower the men’s rates of new high-risk HPV infections, and, in HIV-negative men, it increased the rate at which their immune systems cleared established infections. Still, after two years, many circumcised men were still found to carry a cancer-related HPV: more than 20 percent of HIV-negative men and 55 percent of HIV-positive men.

However, Gray said, given the severity of the problem of HPV and HPV-related cancers in sub-Saharan Africa, “anything we can do to lower the risk is a good thing. It’s possible that circumcision would have benefits for preventing cancers in both men and women.”

The researchers are currently looking at whether circumcision has helped to lower HPV infection in the study participants’ female partners. Gray said that the preliminary results suggest benefits.

The World Health Organization (WHO) currently recommends medically supervised circumcision as one way to lower men’s risk of HIV in countries where heterosexual transmission is common - but in junction with other measures, including HIV education and access to condoms. The WHO also states that men in these countries who are already HIV-positive “should not be denied” circumcision unless there is a medical reason, Gray said.

But the public-health value of circumcision in other countries, including the U.S., is under debate. In the U.S., most HIV infections are related to homosexual sex or IV drug use, and studies have found no good evidence that circumcision lowers HIV transmission among men who have sex with men.

With HPV, in contrast, it’s estimated that most sexually active people in the U.S. will carry some strain of the virus at some point in their lives. However, any risk reduction from circumcision might have little public-health impact in the U.S. - where Pap screening for cervical cancer is routine, penile and anal cancers in men are uncommon, and HPV vaccination is available for girls and women.

The American Academy of Pediatrics does not recommend routine circumcision for newborns, citing insufficient evidence of overall health benefits. The U.S. Centers for Disease Control and Prevention, meanwhile, is currently developing recommendations on adult and infant circumcision for lowering HIV risk.

“My personal feeling,” Gray said, “is that we shouldn’t make any specific recommendations (on newborn circumcision). But we should inform parents of the potential benefits of circumcision.”

But even in countries where circumcision is recommended for HIV prevention, the procedure may have only “marginal” effects on the population prevalence of HPV, according to an editorial published with the studies.

The decrease in HPV prevalence related to circumcision was “significant but modest,” write Drs. Raphael V. Viscidi and Keerti V. Shah, also with Johns Hopkins.

In developed countries where the expensive HPV vaccines are available, the shots are the “preferred public health strategy” for preventing HPV-related diseases, according to the editorialists.

Viscidi has served as a paid consultant to GlaxoSmithKline, which makes Cervarix, one of the two HPV vaccines on the market. Shah has been a consultant to both GlaxoSmithKline and Merck, maker of the other HPV vaccine, Gardasil.

Circumcision is thought to lower the heterosexual transmission of HIV and other sexually transmitted diseases through several mechanisms. One is by reducing the amount of mucosal tissue exposed during sex, which limits the viruses’ access to the body cells they target. Another theory is that the thickened skin that forms around the circumcision scar helps block the viruses’ entry.

SOURCE: Journal of Infectious Diseases, May 15, 2010.