title: Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer.
abstract: BACKGROUND
  To determine whether testing for DNA of oncogenic human papillomaviruses (HPV) is superior to the Papanicolaou (Pap) test for cervical-cancer screening, we conducted a randomized trial comparing the two methods.
  
  
  METHODS
  We compared HPV testing, using an assay approved by the Food and Drug Administration, with conventional Pap testing as a screening method to identify high-grade cervical intraepithelial neoplasia in women ages 30 to 69 years in Montreal and St. John's, Canada. Women with abnormal Pap test results or a positive HPV test (at least 1 pg of high-risk HPV DNA per milliliter) underwent colposcopy and biopsy, as did a random sample of women with negative tests. Sensitivity and specificity estimates were corrected for verification bias.
  
  
  RESULTS
  A total of 10,154 women were randomly assigned to testing. Both tests were performed on all women in a randomly assigned sequence at the same session. The sensitivity of HPV testing for cervical intraepithelial neoplasia of grade 2 or 3 was 94.6% (95% confidence interval [CI], 84.2 to 100), whereas the sensitivity of Pap testing was 55.4% (95% CI, 33.6 to 77.2; P=0.01). The specificity was 94.1% (95% CI, 93.4 to 94.8) for HPV testing and 96.8% (95% CI, 96.3 to 97.3; P<0.001) for Pap testing. Performance was unaffected by the sequence of the tests. The sensitivity of both tests used together was 100%, and the specificity was 92.5%. Triage procedures for Pap or HPV testing resulted in fewer referrals for colposcopy than did either test alone but were less sensitive. No adverse events were reported.
  
  
  CONCLUSIONS
  As compared with Pap testing, HPV testing has greater sensitivity for the detection of cervical intraepithelial neoplasia. (Current Controlled Trials number, ISRCTN57612064 [controlled-trials.com].).
authors.affiliation: Department of Oncology and Epidemiology & Biostatistics, McGill University, Montreal, Canada.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Mayrand
authors.forename: Eliane
authors.initials: E
authors.lastname: Duarte-Franco
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodrigues
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Walter
authors.forename: James
authors.initials: J
authors.lastname: Hanley
authors.forename: Alex
authors.initials: A
authors.lastname: Ferenczy
authors.forename: Sam
authors.initials: S
authors.lastname: Ratnam
authors.forename: François
authors.initials: F
authors.lastname: Coutlée
authors.forename: Eduardo L
authors.initials: EL
authors.lastname: Franco
mesh_terms: D000328:Adult; D000368:Aged; D003127:Colposcopy; D004279:DNA, Viral / Q000032:analysis*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D065006:Papanicolaou Test; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000473:pathology
chemical_list: D004279:DNA, Viral