How does male circumcision protect against HIV infection?

British Medical Journal, June 10, 2000 by Robert Szabo, Roger V Short

How HIV enters the penis

About 70% of men infected with HIV have acquired the virus through vaginal sex, and a smaller number have acquired it from insertive anal intercourse.[7] Thus, on a global scale most men who are HIV positive have acquired the virus via the penis. This raises questions of how HIV enters the penis and why men who are uncircumcised are potentially more susceptible to becoming infected with HIV.

The uncircumcised penis consists of the penile shaft, glans, urethral meatus, inner and outer surface of the foreskin, and the frenulum, the thin band connecting the inner foreskin to the ventral aspect of the glans. A keratinised, stratified squamous epithelium covers the penile shaft and outer surface of the foreskin. This provides a protective barrier against HIV infection. In contrast, the inner mucosal surface of the foreskin is not keratinised[15] and is rich in Langerhans' cells,[10] making it particularly susceptible to the virus. This is particularly important because during heterosexual intercourse the foreskin is pulled back down the shaft of the penis, and the whole inner surface of the foreskin is exposed to vaginal secretions, providing a large area where HIV transmission could take place.

There is controversy about whether the epithelium of the glans in uncircumcised men is keratinised; some authors claim that it is not,[15] but we have examined the glans of seven circumcised and six uncircumcised men, and found the epithelia to be equally keratinised. In circumcised males only the distal penile urethra is lined with a mucosal epithelium. However, this is unlikely to be a common site of infection because it contains comparatively few Langerhans' cells.[10]

Ulcerative or inflammatory lesions of the penile urethra, foreskin, frenulum, or glans that are caused by other sexually transmitted infections may provide additional potential routes for HIV transmission. In uncircumcised males, the highly vascular frenulum is particularly susceptible to trauma during intercourse, and lesions produced by other sexually transmitted infections commonly occur there. Thus, male circumcision further reduces the risk of infection by reducing the synergy that normally exists between HIV and other sexually transmitted infections.[5]

Conclusions

Of the estimated 50 million people infected with HIV worldwide, about half are men, most of whom have become infected through their penises. The inner surface of the foreskin, which is rich in HIV receptors, and the frenulum, a common site for trauma and other sexually transmitted infections, must be regarded as the most probable sites for viral entry in primary HIV infection in men. Although condoms must remain the first choice for preventing the sexual transmission of HIV, they are often not used consistently or correctly, they may break during use, and there may be strong cultural and aesthetic objections to using them. Cultural and religious attitudes towards male circumcision are even more deeply held, but in the light of the evidence presented here circumcising males seems highly desirable, especially in countries with a high prevalence of HIV infection. Although neonatal circumcision is easy to perform, and has a low incidence of complications,[16] it would be 15-20 years before a programme of circumcision had any effect on HIV transmission rates. Circumcision at puberty, as practised by many Muslim communities, would be the most immediately effective intervention for reducing HIV transmission since it would be done before young men are likely to become sexually active.