Circumcision Can Reduce the Risk of Herpes and HPV Infection

Heterosexual men who undergo medical circumcision can significantly
reduce their risk of acquiring two common sexually transmitted
infections — herpes simplex virus type 2 (HSV-2), the cause
of genital herpes, and human papillomavirus (HPV), which can cause
cancer and genital warts, according to a report in the March 26
issue of The New England Journal of Medicine. In the study,
circumcision had no effect on their risk of becoming infected with
the bacterium that causes syphilis, however.

The findings build upon earlier clinical research funded by the
National Institute of Allergy and Infectious Disease (NIAID), part
of the NIH, which found that circumcision decreases a man’s risk
of acquiring HIV infection through heterosexual intercourse by
more than 50 percent (http://www3.niaid.nih.gov/news/newsreleases/2006/AMC12_06.htm).

"Medically supervised adult male circumcision is a scientifically
proven method for reducing a man’s risk of acquiring HIV infection
through heterosexual intercourse," says NIAID Director Anthony
S. Fauci, M.D. "This new research provides compelling evidence
that circumcision can provide some protection against genital herpes
and human papillomavirus infections as well."

The study was conducted by scientists at the Rakai Health Sciences
Program in Uganda in collaboration with researchers at the Johns
Hopkins University Bloomberg School of Public Health in Baltimore,
Makerere University in Kampala, Uganda, and NIAID’s Division of
Intramural Research. The collaborators examined samples from two
parallel clinical trials in Rakai that successfully proved male
circumcision as an HIV prevention method and also assessed the
surgical procedure’s ability to prevent other sexually transmitted
infections, including syphilis and HSV-2. These infections cause
genital ulcers and are associated with an increased risk of HIV
acquisition. The research team also assessed circumcision’s effect
on HPV infections, which can cause anal, cervical and penile cancers
and genital warts.

The two trials, one funded by NIAID and the other by the Bill & Melinda
Gates Foundation, enrolled 3,393 uncircumcised men between the
ages of 15 and 49 who initially tested negative for both HIV and
HSV-2. The men were assigned at random to one of two study groups:
1,684 received immediate circumcision performed by trained medical
professionals in an outpatient setting (intervention group); and
1,709 received medical circumcision after a delay of 24 months
(control group). The researchers evaluated the volunteers at six,
12 and 24 months for HSV-2 and syphilis infection. Additionally,
a subgroup of 697 volunteers (352 participants in the intervention
group; 345 in the control group) was evaluated for HPV infection
at enrollment and at 24 months.

In analyzing the effect of circumcision on HSV-2 acquisition across
both studies, the researchers found that the cumulative probability
of HSV-2 infection was significantly lower among those volunteers
who received immediate circumcision (7.8 percent) than among those
in the control group who were circumcised at 24 months (10.3 percent).
Overall, the researchers found that medically supervised circumcision
reduced the men’s risk of HSV-2 infection by 28 percent.

The combined results from both trials also demonstrated a 35 percent
reduction in HPV prevalence among men in the intervention group.
In evaluating a subgroup of volunteers at 24 months, high-risk
HPV strains associated with certain cancers were detected in 42
of 233 men in the intervention group and in 80 of 287 men in the
control group.

Circumcision did not, however, affect the incidence of syphilis.
At 24 months, syphilis was detected in 50 men in the intervention
group and 45 members of the control group.

"The cumulative scientific evidence supporting the public
health value of medically supervised male circumcision is now overwhelming," says
Thomas C. Quinn, M.D., study co-investigator, chief of the International
HIV/STD Section in NIAID’s Laboratory of Immunoregulation and co-author
of the study. "This new research confirms the substantial
health benefits of male circumcision, including reduced acquisition
of HIV, genital herpes, HPV and genital ulcer disease."

Dr. David Serwadda, co-principal investigator and dean of Makerere
University’s School of Public Health, adds that "these findings
have significant public health implications for the control of
HIV, genital herpes and HPV in areas of high prevalence, such as
Africa, and further suggest that efforts to scale-up male circumcision
could have tremendous benefit."

"The next focus of our research will be to analyze additional
data collected in the Rakai trials to assess the degree to which
male circumcision may reduce transmission of HPV to female sexual
partners," says Johns Hopkins professor Ronald H. Gray, M.D.,
co-principal investigator. "This would be of substantial significance
because HPV causes cervical cancer."

The biological reasons why circumcision may reduce the risk of
HSV-2 and HPV infection, but not syphilis, are not entirely known.
HSV-2 and HPV multiply in epithelial cells found in the surface
skin of the penis, and the foreskin may facilitate virus entry
into those cells. Once circumcision has been performed, the risk
of epithelial infection may be reduced, the authors note. Additionally,
the analysis used to determine the effects of circumcision on syphilis
had limited statistical power, and therefore, it is difficult to
draw a firm conclusion as to whether or not circumcision may reduce
syphilis incidence, the researchers add.

During each clinic visit, volunteers were given physical examinations,
counseled on safe sex practices and offered condoms, voluntary
HIV counseling and testing. Study staff also interviewed each volunteer
to record sociodemographic characteristics and rates of specific
sexual risk behaviors. Volunteers who acquired HIV infection during
the two clinical trials were referred to Rakai Health Science Program
clinics for HIV care funded by the U.S. President’s Emergency Plan
for AIDS Relief. Volunteers who acquired genital ulcers or syphilis
were also provided with appropriate medical care and treatment.

As with most strategies to prevent sexually transmitted infections,
including HIV, adult male circumcision is not completely effective.
Therefore, the authors note, safe sex practices, including consistent
condom use, are still necessary to provide the best protection
against such infections.

NIAID conducts and supports research — at NIH, throughout
the United States, and worldwide — to study the causes of
infectious and immune-mediated diseases, and to develop better
means of preventing, diagnosing and treating these illnesses. News
releases, fact sheets and other NIAID-related materials are available
on the NIAID Web site at http://www.niaid.nih.gov.

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