title: Long term duration of protective effect for HPV negative women: follow-up of primary HPV screening randomised controlled trial.
abstract: OBJECTIVE
  To assess whether the increased sensitivity of screening for human papillomavirus (HPV) may represent overdiagnosis and to compare the long term duration of protective effect against cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in HPV based and cytology based screening.
  
  
  METHODS
  13 year follow-up of the Swedescreen randomised controlled trial of primary HPV screening.
  
  
  METHODS
  Organised cervical screening programme in Sweden.
  
  
  METHODS
  12,527 women aged 32-38 attending organised screening were enrolled and randomised to HPV and cytology double testing (intervention arm, n=6257) or to cytology only, with samples frozen for future HPV testing (control arm, n=6270).
  
  
  METHODS
  Cumulative incidence of CIN2+ and CIN3+ (Kaplan Meier curves). Longitudinal test characteristics were calculated for cytology only, HPV testing only, and cytology and HPV testing combined, adjusting for censoring.
  
  
  RESULTS
  The increased detection of CIN2+ in the intervention arm decreased over time. After six years, the cumulative incidence of CIN3+ was similar in both trial arms, and after 11 years the cumulative incidence of CIN2+ became similar in both arms. The longitudinal sensitivity of cytology for CIN2+ in the control arm at three years was similar to the sensitivity of HPV testing in the intervention arm at five years of follow-up: 85.94% (95% confidence interval 76.85% to 91.84%) v 86.40% (79.21% to 91.37%). The sensitivity of HPV screening for CIN3+after five years was 89.34% (80.10% to 94.58%) and for cytology after three years was 92.02% (80.59% to 96.97%).
  
  
  CONCLUSIONS
  Over long term follow-up, the cumulative incidence of CIN2+ was the same for HPV screening and for cytology, implying that the increased sensitivity of HPV screening for CIN2+ reflects earlier detection rather than overdiagnosis. The low long term risks of CIN3+ among women who tested negative in HPV screening, support screening intervals of five years for such women.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00479375.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, 171 77 Stockholm, Sweden.
authors.forename: K Miriam
authors.initials: KM
authors.lastname: Elfström
authors.forename: Vitaly
authors.initials: V
authors.lastname: Smelov
authors.forename: Anna L V
authors.initials: AL
authors.lastname: Johansson
authors.forename: Carina
authors.initials: C
authors.lastname: Eklund
authors.forename: Pontus
authors.initials: P
authors.lastname: Nauclér
authors.forename: Lisen
authors.initials: L
authors.lastname: Arnheim-Dahlström
authors.forename: Joakim
authors.initials: J
authors.lastname: Dillner
mesh_terms: D000328:Adult; D004279:DNA, Viral / Q000032:analysis*; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000453:epidemiology / Q000821:virology; D015203:Reproducibility of Results; D012189:Retrospective Studies; D013548:Sweden / Q000453:epidemiology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000821:virology; D014626:Vaginal Smears / Q000379:methods*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000453:epidemiology / Q000821:virology
chemical_list: D004279:DNA, Viral