title: Male circumcision decreases acquisition and increases clearance of high-risk human papillomavirus in HIV-negative men: a randomized trial in Rakai, Uganda.
abstract: METHODS
  Uncircumcised human immunodeficiency virus (HIV)-negative men aged 15-49 years were randomized to immediate circumcision (intervention arm, 441 subjects) or delayed circumcision (control arm, 399 subjects). Human papillomavirus (HPV) was detected by Roche HPV Linear Array at enrollment, and at 6, 12, and 24 months. Incident high-risk HPV (HR-HPV) was estimated in men who acquired a new HR-HPV genotype. HR-HPV clearance was determined in men with prior genotype-specific HR-HPV infections. Rate ratios (RRs) and 95% confidence intervals (CIs) of HR-HPV acquisition were estimated by Poisson multiple regression.
  
  
  RESULTS
  Enrollment characteristics were comparable between study groups. HR-HPV incidence was 19.7 cases per 100 person-years (PYs) in the intervention arm (70 cases per 355.8 PYs) and 29.4 cases per 100 PYs (125 cases per 424.8 PYs) in the control arm (RR, 0.67; 95% CI, 0.51-0.89; P = .006). The incidence of multiple HR-HPV infections was 6.7 cases per 100 PYs in the intervention arm and 14.8 cases per 100 PYs in the control arm (RR, 0.45; 95% CI, 0.28-0.73), but there was no significant effect on single infections (RR, 0.89; 95% CI, 0.60-1.30). HR-HPV incidence was lower in the intervention arm for all genotypes and demographic/behavioral subgroups. The clearance of preexisting HR-HPV infections was 215.8 cases per 100 PYs (205 cases per 95 PYs) in the intervention arm and 159.1 cases per 100 PYs (255 cases per 160.25 PYs) in the control arm (adjusted RR, 1.39; 95% CI, 1.17-1.64).
  
  
  CONCLUSIONS
  Male circumcision reduces the incidence of multiple HR-HPV infections and increases clearance of HR-HPV infections in HIV-uninfected men.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00425984 .
authors.affiliation: Department of Population, Family, and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA. rgray@jhsph.edu
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Gray
authors.forename: David
authors.initials: D
authors.lastname: Serwadda
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Kong
authors.forename: Frederick
authors.initials: F
authors.lastname: Makumbi
authors.forename: Godfrey
authors.initials: G
authors.lastname: Kigozi
authors.forename: Patti E
authors.initials: PE
authors.lastname: Gravitt
authors.forename: Stephen
authors.initials: S
authors.lastname: Watya
authors.forename: Fred
authors.initials: F
authors.lastname: Nalugoda
authors.forename: Victor
authors.initials: V
authors.lastname: Ssempijja
authors.forename: Aaron A R
authors.initials: AA
authors.lastname: Tobian
authors.forename: Noah
authors.initials: N
authors.lastname: Kiwanuka
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Moulton
authors.forename: Nelson K
authors.initials: NK
authors.lastname: Sewankambo
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Reynolds
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.forename: Boaz
authors.initials: B
authors.lastname: Iga
authors.forename: Oliver
authors.initials: O
authors.lastname: Laeyendecker
authors.forename: Amy E
authors.initials: AE
authors.lastname: Oliver
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Wawer
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D002944:Circumcision, Male; D005838:Genotype; D015658:HIV Infections; D006801:Humans; D015994:Incidence; D008297:Male; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications / Q000453:epidemiology / Q000635:transmission* / Q000821:virology*; D012725:Sexual Behavior; D013997:Time Factors; D014454:Uganda / Q000453:epidemiology; D055815:Young Adult