title: Effect of circumcision of HIV-negative men on transmission of human papillomavirus to HIV-negative women: a randomised trial in Rakai, Uganda.
abstract: BACKGROUND
  Randomised trials show that male circumcision reduces the prevalence and incidence of high-risk human papillomavirus (HPV) infection in men. We assessed the efficacy of male circumcision to reduce prevalence and incidence of high-risk HPV in female partners of circumcised men.
  
  
  METHODS
  In two parallel but independent randomised controlled trials of male circumcision, we enrolled HIV-negative men and their female partners between 2003 and 2006, in Rakai, Uganda. With a computer-generated random number sequence in blocks of 20, men were assigned to undergo circumcision immediately (intervention) or after 24 months (control). HIV-uninfected female partners (648 of men from the intervention group, and 597 of men in the control group) were simultaneously enrolled and provided interview information and self-collected vaginal swabs at baseline, 12 months, and 24 months. Vaginal swabs were tested for high-risk HPV by Roche HPV Linear Array. Female HPV infection was a secondary endpoint of the trials, assessed as the prevalence of high-risk HPV infection 24 months after intervention and the incidence of new infections during the trial. Analysis was by intention-to-treat. An as-treated analysis was also done to account for study-group crossovers. The trials were registered, numbers NCT00425984 and NCT00124878.
  
  
  RESULTS
  During the trial, 18 men in the control group underwent circumcision elsewhere, and 31 in the intervention group did not undergo circumcision. At 24-month follow-up, data were available for 544 women in the intervention group and 488 in the control group; 151 (27·8%) women in the intervention group and 189 (38·7%) in the control group had high-risk HPV infection (prevalence risk ratio=0·72, 95% CI 0·60-0·85, p=0·001). During the trial, incidence of high-risk HPV infection in women was lower in the intervention group than in the control group (20·7 infections vs 26·9 infections per 100 person-years; incidence rate ratio=0·77, 0·63-0·93, p=0·008).
  
  
  CONCLUSIONS
  Our findings indicate that male circumcision should now be accepted as an efficacious intervention for reducing the prevalence and incidence of HPV infections in female partners. However, protection is only partial; the promotion of safe sex practices is also important.
  
  
  BACKGROUND
  The Bill & Melinda Gates Foundation, National Institutes of Health, and Fogarty International Center.
authors.affiliation: Department of Population, Family, and Reproductive Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21287, USA.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Wawer
authors.forename: Aaron A R
authors.initials: AA
authors.lastname: Tobian
authors.forename: Godfrey
authors.initials: G
authors.lastname: Kigozi
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Kong
authors.forename: Patti E
authors.initials: PE
authors.lastname: Gravitt
authors.forename: David
authors.initials: D
authors.lastname: Serwadda
authors.forename: Fred
authors.initials: F
authors.lastname: Nalugoda
authors.forename: Frederick
authors.initials: F
authors.lastname: Makumbi
authors.forename: Victor
authors.initials: V
authors.lastname: Ssempiija
authors.forename: Nelson
authors.initials: N
authors.lastname: Sewankambo
authors.forename: Stephen
authors.initials: S
authors.lastname: Watya
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Eaton
authors.forename: Amy E
authors.initials: AE
authors.lastname: Oliver
authors.forename: Michael Z
authors.initials: MZ
authors.lastname: Chen
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Reynolds
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Gray
mesh_terms: D000293:Adolescent; D000328:Adult; D002944:Circumcision, Male; D005260:Female; D015658:HIV Infections / Q000150:complications; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications / Q000453:epidemiology / Q000635:transmission*; D015995:Prevalence; D055815:Young Adult