Circumcision may offer men some protection against HPV

Circumcision may reduce a man's risk of infection with human papilloma virus (HPV), according to two separate studies published in the January 1^st edition of the Journal of Infectious Diseases. The first study, which was conducted in South Africa, found that circumcised men have a significantly lower prevalence than uncircumcised men of penile infection with strains of human papilloma virus associated with a high risk of cervical cancer. The second study was conducted in the US and showed that circumcised men had a lower prevalence of anogenital infection with human papilloma virus.

However, the authors of an accompanying editorial adopt a cautious approach about the rolling-out of circumcision to prevent human papilloma virus. They advocate a “wait and see” approach until the results of further large randomised studies are available.

The South African study was originally designed to assess the safety and efficacy of circumcision as a method of HIV prevention and was conducted in Orange Farm, South Africa.

It is estimated that approximately 10% of women worldwide are infected with human papilloma virus. Certain strains of this virus (most notably 16 and 18) are associated with the development of pre-cancerous and cancerous cell changes in the cervix (as well as the anus and rarely the penis).

Cervical cancer is the most common cancer affecting women in resource-limited settings and over 70% of cases of this cancer in Africa have been attributed to high-risk strains of human papilloma virus.

Observational studies have suggested that circumcised men have a lower prevalence of penile human papilloma virus infection than uncircumcised men, but this has never hitherto been shown in a randomised control trial.

Investigators from the ANRS 1265 study, originally designed to measure the safety and effectiveness of male circumcision as a method of HIV prevention, designed a sub-study to see if male circumcision was also protective against high-risk strains of human papilloma virus.

A total of 3274 uncircumcised men were recruited to the study between 2002 and 2004. They were randomised to be circumcised immediately or to have circumcision delayed until the end of follow-up. All the men were aged between 18 and 24 and had regular clinic visits to test for HIV seroconversion and other sexually transmitted infections.

The sub-study to determine if circumcision was protective against high-risk strains of human papilloma virus involved 1264 men. They had urethral swabs taken in 2005 to test for the presence of these strains and were followed-up for a median of 647 days.

At the end of follow-up, the prevalence of high-risk human papilloma virus infection was significantly lower in circumcised (14%) than uncircumcised men (23%). The investigators’ statistical analysis showed that circumcised men had a significantly reduced risk of infection with such strains of human papilloma virus compared to uncircumcised men (adjusted risk ratio: 0.62, 95% CI: 0.47-0.80, p < 0.001).

The protective effect of circumcision against high-risk strains of human papilloma virus remained unchanged when the investigators excluded men who seroconverted for HIV from their analysis (p < 0.009).

Furthermore, they found that circumcised men also had a reduced risk of infection with multiple high-risk strains of human papilloma virus (4% vs 10% for uncircumcised men, p < 0.001).

Rates of gonorrhoea were similar between circumcised and uncircumcised men (see separate aidsmap.com news report) and the two groups of men also reported similar numbers of lifetime sexual partners (mean, four). Furthermore, similar proportions of circumcised and uncircumcised men reported consistent condom use (17% vs 20%). The investigators believe that such similarities mean the protective effects of male circumcision cannot be attributed to differences in sexual activity between the two groups of men.

“We have demonstrated an independent and partial protective effect of male circumcision on the prevalence of high-risk human papilloma virus”, write the investigators.

Although vaccines against high-risk strains of human papilloma virus have recently become available, the investigators note that their cost is likely to be prohibitive for many poorer countries. They conclude, “the protective effects of male circumcision may supplant human papilloma virus vaccines in terms of genotype coverage and target-group age range.”

The US study involved 463 men and was conducted between 2002 and 2005. The men reported sex with a woman in the previous year. All provided a semen sample and had a physical examination to check for the presence of anogenital warts or lesions. If any warts were present they were swabbed for genotyping. The examining physician also recorded the men’s circumcision status (84% circumcised).

Circumcision was strongly associated with a reduced risk of detecting any human papilloma virus (adjusted odds ratio [AOR]: 0.44, 5% CI: 0.23-0.82) or high-risk strains (AOR: 0.47; 95% CI: 0.22-0.99), at the top of the penis and in the urethra.

Circumcision seemed to be associated with a reduced risk of any human papilloma virus infection or infection with high-risk strains on the shaft of the penis (p = 0.05).

However, although circumcised men had a reduced risk of human papilloma virus infection on the scrotum, anal canal, perianal area and in semen, this reduction was not statistically significant.

The authors of an accompanying editorial are cautious about the possible public health benefits of circumcision as a method of preventing human papilloma virus.

They write: “Given the range of estimates of the protective effects from observational studies and the fact that we have data from only 1 randomised trial, it would be premature to promote circumcision as a way to prevent human papilloma virus infection in men and as a possible way to protect their female sex partners from infection.” Two ongoing trials in Kenya and Uganda should provide further information.