Male circumcision provides some protection against high-risk HPV, but public health benefits unclear

Adult male circumcision appears to have some protective effect against high-risk strains of human papillomavirus, according to two studies published in the May 15^th edition of the Journal of Infectious Diseases.

In HIV-positive men, circumcision reduced the prevalence and incidence of multiple high-risk penile human papillomavirus infections. Circumcision also had these benefits for HIV-negative men, and was also associated with clearance of infections.

Randomised controlled trials have shown that male circumcision can reduce the risk of HIV infection by between 50 and 60%.

One of these studies was conducted in Rakai, Uganda, and its investigators wished to see if male circumcision was also protective against high-risk strains of human papillomavirus.

The therefore undertook two prospective, randomised controlled studies. One involved 210 HIV-positive men, the other 840 HIV-negative men.

Approximately half of the men in both studies were randomised to be circumcised.

On entry to the study, and then after six, twelve and 24 months of follow-up, the men were screened for penile infection with strains of human papillomavirus associated with a high risk of ano-genital cancers.

The HIV-positive study

At baseline, the prevalence of high-risk penile human papillomavirus infection was comparable in the HIV-positive men randomised to be circumcised (72%) and the controls (77%). Similar proportions of men in both study arms were infected with two or more high-risk strains of the virus (50% vs 48%).

After 24 months of follow-up, 55% of circumcised men were infected with at least one high-risk strain compared to 77% of uncircumcised men.

This difference in prevalence was not significant.

However, the prevalence of high-risk infections declined significantly amongst the men undergoing circumcision (p = 0.02), but remained stable in the control arm.

In addition, at the end of follow-up, only 22% of circumcised men had multiple high-risk infections compared to 43% of individuals who remained uncircumcised.

Circumcision did not reduce the risk of infection with a single, new high-risk strain of human papillomavirus. However, only 10% of circumcised men were infected with multiple new strains, compared to 24% of men in the control arm (p = 0.01).

Comparable proportions of circumcised and uncircumcised men cleared their high-risk infections (76% vs 71%).

The impact of circumcision on low-risk strains of human papilloma virus was also assessed. At baseline, the prevalence of such infections was similar in the two arms of the study (86% vs 83%). After 24 months, this had fallen to 49% in the circumcised men, but remained relatively static at 77% in the uncircumcised men.

“In summary, we conclude that circumcision of HIV-infected men significantly reduced the incidence and prevalence of multiple high-risk… and low-risk human papilloma virus infections and thus provides a direct health benefit to those individuals and potentially to their sex partners,” write the investigators

The HIV-negative study

Prevalence of high-risk infections was similar in the two arms at baseline (78% vs 77%).

Incidence of any new high-risk infections was 20 cases per 100 person years in the circumcised patients compared to 29 cases per 100 person years in the control arm, a significant difference (p = 0.006).

The incidence of multiple new high-risk infections was also lower for the circumcised than the uncircumcised men (7 vs 15 cases per 100 person years). After adjustment for potentially confounding factors, circumcised men had a significant 33% reduction in their risk of incident infections (p = 0.008).

Circumcision associated with increased clearance of existing infections (216 vs 159 cases per 100 person years, adjusted risk ratio, 1.39, 95% CI, 1.17 to 1.64).

The investigators comment, “male circumcision may potentially reduce exposure of female partners to high-risk human papilloma virus.”

What is the significance of the findings?

The authors of an editorial accompanying these studies believe that their findings “strengthen the case for neonatal circumcision of male newborns”.

However, they add, “adult male circumcision is not likely to become a recommended way to control human papilloma virus infection and disease in men and women…highly efficacious prophylactic vaccines…make[s] vaccination the preferred public health strategy for prevention of cervical cancer and other human papilloma virus-associated malignancies, as well as ano-genital warts.”