title: HPV DNA testing in population-based cervical screening (VUSA-Screen study): results and implications.
abstract: BACKGROUND
  Human papillomavirus (HPV) testing is more sensitive than cytology for detecting high-grade cervical intraepithelial neoplasia (CIN). We evaluated the performance of high-risk HPV (hrHPV) testing in routine screening.
  
  
  METHODS
  In all, 25,871 women (29-61) enrolled in our population-based cohort study were offered both cytology and hrHPV testing. High-risk HPV-positive women with normal cytology and an age-matched subcohort of hrHPV-negative women with normal cytology were invited for repeat testing after 1 and/or 2 years and were referred for colposcopy if they presented with abnormal cytology and/or a positive hrHPV test. The hrHPV-positive women with borderline or mild dyskaryosis (BMD) and all women with moderate dyskaryosis or worse (>BMD) were directly referred for colposcopy. Women with BMD and an hrHPV-negative test were advised to repeat cytology at 6 and 18 months and were referred for colposcopy if the repeat cytology test was abnormal. The main outcome measure was CIN grade 3 or worse (CIN3+). Results were adjusted for non-attendance at repeat testing.
  
  
  RESULTS
  The hrHPV-positive women with abnormal cytology had a CIN3+ risk of 42.2% (95% confidence interval (CI): 36.4-48.2), whereas the hrHPV-positive women with normal cytology had a much lower risk of 5.22% (95% CI: 3.72-7.91). In hrHPV-positive women with normal cytology, an additional cytology step after 1 year reduced the CIN3+ risk to only 1.6% (95% CI: 0.6-4.9) if the repeat test was normal. The CIN3+ risk in women with hrHPV-positive normal cytology was higher among women invited for the first time (29-33 years of age) (9.1%; 95% CI: 5.6-14.3) than among older women (3.0%; 95% CI: 1.5-5.5).
  
  
  CONCLUSIONS
  Primary hrHPV screening with cytology triage in women aged 30 years is an effective way to stratify women on CIN3+ risk and seems a feasible alternative to cytological screening. Repeat cytology after 1 year for hrHPV-positive women with normal cytology is however necessary before returning women to routine screening.
authors.affiliation: Department of Pathology, VU University Medical Center, PO Box 7057, 1007 Amsterdam, The Netherlands.
authors.forename: D C
authors.initials: DC
authors.lastname: Rijkaart
authors.forename: J
authors.initials: J
authors.lastname: Berkhof
authors.forename: F J
authors.initials: FJ
authors.lastname: van Kemenade
authors.forename: V M H
authors.initials: VM
authors.lastname: Coupe
authors.forename: L
authors.initials: L
authors.lastname: Rozendaal
authors.forename: D A M
authors.initials: DA
authors.lastname: Heideman
authors.forename: R H M
authors.initials: RH
authors.lastname: Verheijen
authors.forename: S
authors.initials: S
authors.lastname: Bulk
authors.forename: W
authors.initials: W
authors.lastname: Verweij
authors.forename: P J F
authors.initials: PJ
authors.lastname: Snijders
authors.forename: C J L M
authors.initials: CJ
authors.lastname: Meijer
mesh_terms: D000328:Adult; D052685:Alphapapillomavirus / Q000235:genetics; D002584:Cervix Uteri / Q000166:cytology / Q000473:pathology / Q000821:virology; D003584:Cytological Techniques; D004279:DNA, Viral / Q000032:analysis; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000517:prevention & control / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000517:prevention & control / Q000821:virology
chemical_list: D004279:DNA, Viral