Circumcision and STIs

US experts have argued that “circumcision should be routinely considered as a way to reduce the risk of sexually transmitted infections,” BBC News reported. It said that circumcision is already known to greatly reduce the risk of infection from HIV, and researchers have now found that it also reduces the risk of herpes by 25%, and human papillomavirus (HPV) by a third. However, the BBC says that UK experts disagree with their US counterparts, and that “pushing circumcision as a solution sent the wrong message”.

There is some evidence that circumcision reduces the risk and spread of STIs. However, this study was carried out in Uganda, and its findings are not directly comparable to the UK. The main reason for this is the large difference in rates of STIs between the two countries. Further research in countries with a more comparable rate of STIs would give a better indication. When having sex, a condom remains the best way to avoid contracting an STI.

It is also important not to conclude that the results would be the same in other subgroups, such as men who have sex with men, or men who are circumcised as newborns. It could be that the benefits of circumcision differ among different groups.

Where did the story come from?

The research was carried out by Dr Aaron A.R. Tobian and colleagues from the Johns Hopkins University in Baltimore, US and colleagues from the Institute of Public Health at Makerere University and the Rakai Health Sciences Program in Uganda. The study was supported by grants from a range of organisations, including the National Institutes of Health and the Bill and Melinda Gates Foundation. The study was published in the peer-reviewed New England Journal of Medicine .

What kind of scientific study was this?

The study investigated whether male circumcision prevents certain sexually transmitted infections (STIs) in HIV-negative adolescent boys and men. The STIs included herpes simplex virus type 2 (HSV-2), human papillomavirus (HPV) infections as well as syphilis.

The data for this study was obtained from two previous randomised controlled trials, known as the Rakai-1 and Rakai-2 trials, and re-analysed. The Rakai-1 and Rakai-2 trials were carried out by the same researchers, and investigated circumcision and the rate of HIV infection and other STIs. These two independent trials shared the same design and used identical methods. They ran alongside each other, with Rakai-1 running from September 2003 to September 2005, and Rakai-2 running from February 2004 to December 2006. Together, both trials enrolled 6,369 males between 15 and 49 years old.

Of the 6,396 males who were initially screened in both the Rakai-1 and Rakai-2 trials, 3003 were excluded from the recent analyses because they had tested positive or had indeterminate results in tests for the HSV-2 or HIV-1 viruses.

After these exclusions, 3,393 males were included in this study and randomly allocated to either immediate circumcision (1,684 males) or circumcision after a 24-month wait (after the study has finished). In the immediate circumcision group, 134 did not eventually get circumcised, and in the waiting group 32 were circumcised elsewhere during the study.

The researchers tested the men for HSV-2 infection, HIV infection and syphilis at the start of the study and six, 12, and 24 months later. The men were also examined and interviewed at these visits. In addition, the researchers evaluated a subgroup of men for HPV infection at the beginning of the study and after 24 months.

What were the results of the study?

After 24 months, the circumcised men had a 7.8% overall chance of testing positive for the genital herpes virus, compared to a 10.3% chance in the uncircumcised group (adjusted hazard ratio 0.72, 95% confidence interval [CI] 0.56 to 0.92; P = 0.008).

In the circumcised group, the prevalence of high-risk HPV genotypes was 18% compared to 27.9% in the uncircumcised group (adjusted risk ratio 0.65, 95% CI 0.46 to 0.90; P = 0.009).

There was no significant difference between the two study groups in the proportion that developed syphilis (adjusted hazard ratio 1.10, 95% CI 0.75 to 1.65; P = 0.44).

What interpretations did the researchers draw from these results?

The researchers say that “in addition to decreasing the incidence of HIV infection, male circumcision significantly reduced the incidence of HSV-2 infection and the prevalence of HPV infection”.

They say that other related research shows that male circumcision decreases the rates of HIV, HSV-2, and HPV infections in men. In their female partners, it reduces infections of trichomoniasis, bacterial vaginosis, other sexually transmitted infections. The researchers conclude that their findings “underscore the potential public health benefits of the procedure”.

What does the NHS Knowledge Service make of this study?

This study has important implications for the control of sexually transmitted infections in Africa, but researchers and commentators seem to disagree about the implications closer to home and in other population groups not tested in the study.

For example, an editorial written by doctors in the US and published in the same journal said, "These new data should prompt a major reassessment of the role of male circumcision.” They suggest that maternity health providers have a responsibility to educate mothers and fathers about the benefits of circumcision soon after birth.

However, UK commentators are sceptical. This seems to be because it is unclear how circumcision might protect against STIs. There are several theories for this:

Following circumcision, the skin covering the head of the penis becomes tougher and may protect against "microtears" during sex, which can provide a point of entry for germs.
The lining of the foreskin, removed during circumcision, may be the point at which germs enter the underlying skin cells.
After sex, the foreskin may prolong the amount of time that tender skin is exposed to germs.

Other points to note about this study are that:

After six months, reported condom use was higher in the circumcision group than in the control group (P<0.001), but no significant differences in condom use between the two study groups were observed after this. As condoms are known to protect against STIs, the researchers took this into account in their analysis. However, the fact that there was a difference between the groups implies that the circumcised group might have been more aware or careful with respect to the infection risk. This would create inaccuracies in the study, despite the adjustment for condom use.
About 18% of men from both groups were lost to follow-up, died or were enrolled for an insufficient period (less than 24 months) for the analysis. This is a large proportion of those who enrolled, and it is possible that there were differences in the rates of infection between those completing the trial and those who dropped out, which could influence the overall results.
One of the commentators’ main concerns over this study is that it was carried out in Uganda, and the results may not be directly applicable to more developed countries. It is also important not to conclude that the results would be the same in other subgroups, such as men who have sex with men, and men who are circumcised as newborns. It could be that the benefits of circumcision differ in different groups.

The differences between the US and UK interpretations of this study may be more cultural than scientific, and circumcision has historically been much more common in the US. More research in areas with a lower prevalence of HIV will be needed in order to test the relevance of this study outside of Uganda.