Larger foreskin size is associated with an increased risk of becoming infected with HIV, investigators from the Rakai circumcision study report in the October edition of AIDS.
“Larger foreskin size is a risk factor for HIV acquisition in uncircumcised men,” comment the investigators.
Several African studies have shown that circumcised men have a lower risk of becoming infected with HIV than uncircumcised men. The Rakai study was one of these studies, and showed that men who underwent circumcision at the beginning of the study had a 48% lower risk of infection than men randomised to remain uncircumcised.
Investigators from the Rakai circumcision study hypothesised that the size of an individual's foreskin may be associated with an increased risk of HIV infection, due to the larger surface area containing cells vulnerable to HIV infection.
They therefore analysed men in the clinical trial who had previously taken part in a cohort study to see if they could find an association between the size of the foreskin measured at the time of circumcision and the risk of HIV acquisition in uncircumcised men prior to the removal of their foreskin.
They conducted the retrospective analysis in men who had initially been recruited to the Rakai community cohort study, tested for HIV at baseline and followed for a median of four years prior to enrolling in the clinical trial and undergoing medical circumcision.
A total of 965 men were included in the study. In the clinical trial they were randomised to be circumcised immediately or to have circumcision delayed for two years.
Foreskin area was measured in centimetres squared (cm2) by multiplying the length of the foreskin by the width.
In addition, the foreskin surface areas were categorised into quartiles:
- Lowest 25% in surface area (7 to 26.3 cm2).
- 26 to 50% (26.4 to 35 cm2).
- 51 to 75% (35.1 to 45.5 cm2).
- Above 75% (45.6 to 99.8cm2).
There were 48 new HIV infections. The median foreskin area was larger in those who became infected with HIV compared with those who did not (41.5 vs 35 cm2).
Furthermore, the mean foreskin area was significantly higher among those who seroconverted than those who did not (43.3 vs 36.8 cm2).
The investigators also noticed than men aged 24 and younger had smaller foreskin areas compared to both men in their late 20s and those in their 30s and 40s.
HIV incidence was lowest amongst men with foreskin surface areas in the lowest quartile (0.8 per 100 person years), and incidence increased with foreskin surface area, being 2.48 per 100 person years amongst individuals in the upper quartile (p
After adjustment for possible confounding factors, the investigators found that individuals with a foreskin area above 45.6 cm2 had a significantly increased risk of becoming infected with HIV compared to men with the smallest foreskin surface area (adjusted risk ratio, 2.37, 95% CI: 1.05 to 5.31, p = 0.04).
Men aged 25 and older (p = 0.01), those with a lower level of education (p = 0.03), and Catholics (p = 0.01) also had a higher risk of HIV seroconversion.
“We found that the mean foreskin surface area among men who seroconverted to HIV was significantly larger than among men who remained uninfected, and that the risk of HIV acquisition was significantly increased among men with foreskins in the upper quartile of surface area compared with men in the lowest quartile of foreskin area,” write the authors.
They conclude, “a larger foreskin area was associated with an increased risk of HIV acquisition”, a finding which they suggest has implications for circumcision providers who “should avoid leaving excess residual foreskin tissue after circumcision”. Although this is a particular problem with the forceps-guided procedure used in the study, because it leaves a margin of mucosal skin of up to 1cm, the investigators also note that this remaining mucosal surface is still substantially smaller than that measured in the lowest-risk group in this study.
Kigozi G et al. Foreskin surface area and HIV acquisition in Rakai, Uganda (size matters). AIDS 23: 2209-13, 2009.