title: Human papillomavirus and Papanicolaou tests to screen for cervical cancer.
abstract: BACKGROUND
  Screening for cervical cancer based on testing for human papillomavirus (HPV) increases the sensitivity of detection of high-grade (grade 2 or 3) cervical intraepithelial neoplasia, but whether this gain represents overdiagnosis or protection against future high-grade cervical epithelial neoplasia or cervical cancer is unknown.
  
  
  METHODS
  In a population-based screening program in Sweden, 12,527 women 32 to 38 years of age were randomly assigned at a 1:1 ratio to have an HPV test plus a Papanicolaou (Pap) test (intervention group) or a Pap test alone (control group). Women with a positive HPV test and a normal Pap test result were offered a second HPV test at least 1 year later, and those who were found to be persistently infected with the same high-risk type of HPV were then offered colposcopy with cervical biopsy. A similar number of double-blinded Pap smears and colposcopies with biopsy were performed in randomly selected women in the control group. Comprehensive registry data were used to follow the women for a mean of 4.1 years. The relative rates of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected at enrollment and at subsequent screening examinations were calculated.
  
  
  RESULTS
  At enrollment, the proportion of women in the intervention group who were found to have lesions of grade 2 or 3 cervical intraepithelial neoplasia or cancer was 51% greater (95% confidence interval [CI], 13 to 102) than the proportion of women in the control group who were found to have such lesions. At subsequent screening examinations, the proportion of women in the intervention group who were found to have grade 2 or 3 lesions or cancer was 42% less (95% CI, 4 to 64) and the proportion with grade 3 lesions or cancer was 47% less (95% CI, 2 to 71) than the proportions of control women who were found to have such lesions. Women with persistent HPV infection remained at high risk for grade 2 or 3 lesions or cancer after referral for colposcopy.
  
  
  CONCLUSIONS
  The addition of an HPV test to the Pap test to screen women in their mid-30s for cervical cancer reduces the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected by subsequent screening examinations. (ClinicalTrials.gov number, NCT00479375 [ClinicalTrials.gov].).
authors.affiliation: Department of Medical Microbiology, Malmö University Hospital, Lund University, Malmö, Sweden.
authors.forename: Pontus
authors.initials: P
authors.lastname: Naucler
authors.forename: Walter
authors.initials: W
authors.lastname: Ryd
authors.forename: Sven
authors.initials: S
authors.lastname: Törnberg
authors.forename: Anders
authors.initials: A
authors.lastname: Strand
authors.forename: Göran
authors.initials: G
authors.lastname: Wadell
authors.forename: Kristina
authors.initials: K
authors.lastname: Elfgren
authors.forename: Thomas
authors.initials: T
authors.lastname: Rådberg
authors.forename: Björn
authors.initials: B
authors.lastname: Strander
authors.forename: Bo
authors.initials: B
authors.lastname: Johansson
authors.forename: Ola
authors.initials: O
authors.lastname: Forslund
authors.forename: Bengt-Göran
authors.initials: BG
authors.lastname: Hansson
authors.forename: Eva
authors.initials: E
authors.lastname: Rylander
authors.forename: Joakim
authors.initials: J
authors.lastname: Dillner
mesh_terms: D000328:Adult; D003127:Colposcopy; D004279:DNA, Viral / Q000032:analysis*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008403:Mass Screening; D065006:Papanicolaou Test; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis*; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000517:prevention & control; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000473:pathology / Q000517:prevention & control
chemical_list: D004279:DNA, Viral