CIRCUMCISED HIV-INFECTED MEN AND HPV TRANSMISSION

Thursday, 16th of June 2011

‘Male circumcision is important for reduction of not only HIV infection but also HPV infection in HIV-negative men and their female partners. However, its efficacy in reducing HPV transmission seems restricted to HIV-negative men; thus, the results of increasing numbers of reports suggest the need for early circumcision to achieve maximum effectiveness in populations with a high incidence of HIV and cervical cancer. To achieve maximum reductions in HIV and HPV infections and their related diseases in women, both male circumcision and HPV vaccination of the population should be delivered before sexual debut.’

The Lancet Infectious Diseases, Early Online Publication, 12 April 2011

This comment by Guiliano and colleagues, text also at http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(11)70038-X/fulltext
refers to a study by Tobian and colleagues, text and graphics available at
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(11)70038-X/fulltext

Circumcised HIV-infected men and HPV transmission

Original Text

AR Giuliano a , MF Schim van der Loeff b, AG Nyitray a

Countries with high incidences of HIV also have the highest incidence of cancers related to human papillomavirus (HPV). This association is particularly true in southern Africa, where the HIV incidence in young women (about five per 100 person-years of observation in some regions) and the cervical cancer incidence (about 40 per 100 000 per year) are among the highest in the world. Interventions that can reduce the rates of HIV infection, HPV infection, or both, are urgently needed.

So far, the results of few trials of HIV preventive interventions have shown efficacy in reduction of HIV infection in men or women.1—4 Circumcision of men is one of the few interventions, shown in three separate randomised controlled trials in Africa, to reduce the rates of HIV and HPV infection in men,5—9 and transmission of HPV to their female sexual partners.10 However, circumcision of HIV-infected men did not reduce HIV transmission to their female partners.11 Altogether these data lead to the question of what is the ideal time for male circumcision to optimise prevention of infection and disease. Data presented by Aaron Tobian and colleagues12 in The Lancet Infectious Diseases suggest that because acquisition of HIV infection is highest among young adults (aged 18—30 years), the greatest population benefit of male circumcision is likely to be achieved if done before sexual debut and first exposure to HIV and HPV.

Tobian and colleagues show that circumcision of HIV-infected men does not reduce HPV transmission to their female partners. Among 211 female partners of HIV-infected men who were randomly assigned to circumcision and 171 female partners of HIV-infected male controls, HPV was assessed in vaginal swabs collected at enrolment and at 1-year and 2-year study visits. Irrespective of the analysis (intention to treat or as treated) or the HIV status of the female partner at study entry, circumcision of men did not reduce HPV transmission to their female partners. The many factors that could have contributed to the lack of efficacy include difficulties in identification and enrolment of a large sample of eligible partners secondary to the index male partner who was randomly assigned to circumcision, potential selection bias attributable to differential participation of female partners of men assigned to the intervention group compared with the control group, partnership dissolution and changes during the trial, a high rate of loss to follow-up, and a long interval between tests of HPV status. Because the median duration of genital infections in both men and women is about 7—9 months,13 detection of HPV might have been missed with a 12-month examination window. However, a more likely explanation for the lack of efficacy of male circumcision on male-to-female HPV transmission relates to the high prevalence of HPV among the HIV-infected men (73% in the intervention group, and 69% in the control group), and the high prevalence of HIV among the female partners (>60%). Although a CD4 count of more than 350 cells per μL was an inclusion criterion for the men, subtle immunological defects could have affected the natural history of HPV infection, which, together, might result in differential risks for acquiring a new HPV infection, as well as increasing the duration of newly acquired and prevalent HPV infections.14, 15 The high and sustained HPV prevalence among HIV-infected individuals is likely to have overwhelmed any preventive effect that circumcision could exert, as the authors point out.

Male circumcision is important for reduction of not only HIV infection but also HPV infection in HIV-negative men and their female partners. However, its efficacy in reducing HPV transmission seems restricted to HIV-negative men; thus, the results of increasing numbers of reports suggest the need for early circumcision to achieve maximum effectiveness in populations with a high incidence of HIV and cervical cancer. To achieve maximum reductions in HIV and HPV infections and their related diseases in women, both male circumcision and HPV vaccination of the population should be delivered before sexual debut.

MFSvdL and ARG have acted as paid consultants to Merck, the manufacturer of HPV vaccine. Additionally, ARG has received research funding from Merck and is on their speakers' bureau. AGN has received research funding from Merck.

References

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a Department of Cancer Epidemiology, H Lee Moffitt Cancer Center, Tampa, FL 33612, USA

b GGD Amsterdam and Academic Medical Center, Amsterdam, Netherlands