title: Safety of extending screening intervals beyond five years in cervical screening programmes with testing for high risk human papillomavirus: 14 year follow-up of population based randomised cohort in the Netherlands.
abstract: OBJECTIVE
  To provide an early risk assessment of extending screening intervals beyond five years for a human papillomavirus (HPV) based cervical screening programme in the Netherlands.
  
  
  METHODS
  14 year follow-up of a population based randomised cohort from the POBASCAM randomised trial.
  
  
  METHODS
  Organised cervical screening in the Netherlands, based on a programme of three screening rounds (each round done every five years).
  
  
  METHODS
  43 339 women aged 29-61 years with a negative HPV and/or negative cytology test participating in the POBASCAM trial.
  
  
  METHODS
  Women randomly assigned to HPV and cytology co-testing (intervention) or cytology testing only (control), and managed accordingly.
  
  
  METHODS
  Cumulative incidence of cervical cancer and cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+). Associations with age were expressed as incidence rate ratios. In HPV positive women, reductions in CIN3+ incidence after negative cytology, HPV type 16/18 genotyping, and/or repeat cytology were estimated.
  
  
  RESULTS
  The cumulative incidence of cervical cancer (0.09%) and CIN3+ (0.56%) among HPV negative women in the intervention group after three rounds of screening were similar to the cumulative among women with negative cytology in the control group after two rounds (0.09% and 0.69%, respectively). Cervical cancer and CIN3+ risk ratios were 0.97 (95% confidence interval 0.41 to 2.31, P=0.95) and 0.82 (0.62 to 1.09, P=0.17), respectively. CIN3+ incidence was 72.2% (95% confidence interval 61.6% to 79.9%, P<0.001) lower among HPV negative women aged at least 40 years than among younger women. No significant association between cervical cancer incidence and age could be demonstrated. CIN3+ incidence among HPV positive women with negative cytology, HPV 16/18 genotyping, and/or repeat cytology was 10.4 (95% confidence interval 5.9 to 18.4) times higher than among HPV negative women.
  
  
  CONCLUSIONS
  Long term incidences of cervical cancer and CIN3+ were low among HPV negative women in this study cohort, and supports an extension of the cervical screening interval beyond five years for women aged 40 years and older. HPV positive women with subsequent negative cytology, HPV16/18 genotyping, and/or repeat cytology have at least a fivefold higher risk of CIN3+ than HPV negative women, indicating that HPV based programmes with long intervals (>five years) should be implemented with risk stratification.Trial registration POBASCAM trial number ISRCTN20781131.
authors.affiliation: Department of Pathology, VU University Medical Centre, Amsterdam, Netherlands Department of Obstetrics and Gynaecology, VU University Medical Centre, Amsterdam, Netherlands.
authors.forename: Maaike G
authors.initials: MG
authors.lastname: Dijkstra
authors.affiliation: Department of Pathology, VU University Medical Centre, Amsterdam, Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: van Zummeren
authors.affiliation: Department of Pathology, VU University Medical Centre, Amsterdam, Netherlands.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Rozendaal
authors.affiliation: Department of Pathology, Erasmus MC, Rotterdam, Netherlands.
authors.forename: Folkert J
authors.initials: FJ
authors.lastname: van Kemenade
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, Rotterdam, Netherlands.
authors.forename: Theo J M
authors.initials: TJ
authors.lastname: Helmerhorst
authors.affiliation: Department of Pathology, VU University Medical Centre, Amsterdam, Netherlands.
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Snijders
authors.affiliation: Department of Pathology, VU University Medical Centre, Amsterdam, Netherlands.
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Centre, PO box 7057, 1007MB Amsterdam, Netherlands h.berkhof@vumc.nl.
authors.forename: Johannes
authors.initials: J
authors.lastname: Berkhof
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000453:epidemiology* / Q000473:pathology / Q000821:virology; D000328:Adult; D000359:Aftercare; D000367:Age Factors; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000453:epidemiology* / Q000473:pathology / Q000821:virology; D055088:Early Detection of Cancer; D005260:Female; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D052161:Human papillomavirus 18 / Q000302:isolation & purification*; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D018570:Risk Assessment; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000453:epidemiology* / Q000473:pathology / Q000821:virology; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000453:epidemiology* / Q000473:pathology / Q000821:virology