title: Colposcopy:  still useful in microbicide safety trials?
abstract: BACKGROUND
  Colposcopy is used to evaluate vaginal microbicides, but its link to risk of HIV is unknown. This reanalysis of 9 safety studies determined the impact of omitting colposcopy on the number of findings detected and assessed whether colposcopy was useful in identifying nonoxynol-9 (N-9) as an unsafe product in one study.
  
  
  METHODS
  Product-related findings seen with naked eye and colposcopy or by colposcopy alone were evaluated. Using data from one study, the ratio of findings in N-9 users to those in hydroxyethylcellulose (HEC) users was compared for findings seen by naked eye and colposcopy versus findings detected only by colposcopy.
  
  
  RESULTS
  Of the 403 finding observations in the 9 studies, 173 (43%) would have been missed without colposcopy. Data from the N-9/HEC study showed that without colposcopy, there would have been 7 times as many observations in the N-9 group as in the HEC group (63 vs. 9). With colposcopy, the N-9/HEC ratio was 13:9 or 1.4. Considering epithelial integrity, finding type, and size showed similar patterns, except that among the smallest findings (<5 mm), the N-9/HEC ratio was 1.2 by naked eye and nearly the same at 1.4 by colposcopy.
  
  
  CONCLUSIONS
  Colposcopy was not helpful in identifying an unsafe product: the conclusions reached using naked eye examination alone were more alarming regarding the safety of N-9 than reached by including colposcopy. Recommendations include: (1) naked eye examinations should be continued in microbicide studies; (2) colposcopy may be considered for early studies, such as first-in-human studies, but has no place in large studies; and (3) colposcopy should be replaced as soon as possible with a more objective validated biomarker of HIV risk.
authors.affiliation: CONRAD, Arlington, VA, USA. cmauck@conrad.org
authors.forename: Christine K
authors.initials: CK
authors.lastname: Mauck
authors.forename: Debra H
authors.initials: DH
authors.lastname: Weiner
authors.forename: Jaim Jou
authors.initials: JJ
authors.lastname: Lai
authors.forename: Jill L
authors.initials: JL
authors.lastname: Schwartz
mesh_terms: D000282:Administration, Intravaginal; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects*; D003127:Colposcopy / Q000009:adverse effects* / Q000379:methods; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D017408:Guidelines as Topic; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D008297:Male; D017137:Nonoxynol / Q000008:administration & dosage / Q000009:adverse effects*; D015588:Observer Variation; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome; D014621:Vagina / Q000473:pathology*
chemical_list: D000890:Anti-Infective Agents; D013501:Surface-Active Agents; D017137:Nonoxynol