title: Human papillomavirus type-specific 18-month risk of high-grade cervical intraepithelial neoplasia in women with a normal or borderline/mildly dyskaryotic smear.
abstract: BACKGROUND
  High-risk human papillomavirus (hrHPV) DNA testing is an increasingly used instrument in cervical cancer prevention along cervical cytology. The inclusion of hrHPV testing in cervical screening requires efficient management as many hrHPV infections are transient. We investigated the potential value of hrHPV genotyping in normal and borderline/mildly dyskaryotic (BMD) smears.
  
  
  METHODS
  From a screening population of 44,102 women in the Netherlands, we included hrHPV-positive women with a normal or BMD smear. We assessed the type-specific 18-month risk of high-grade cervical intraepithelial neoplasia (CIN).
  
  
  RESULTS
  In hrHPV-positive women, 18-month risk of CIN grade 3 or invasive cancer (> or =CIN3) was 6% [95% confidence interval (95% CI), 4-9] after normal cytology and 20% (95% CI, 16-25) after BMD. If positive for HPV16, > or =CIN3 risks were 14% (95% CI, 9-21) and 37% (95% CI, 28-48), respectively. In the subset of hrHPV-positive women without HPV16, HPV18 was associated with an increased risk of high-grade CIN after normal cytology and HPV31 and HPV33 were associated with an increased risk, particularly after BMD. HPV16 and HPV18 were also associated with an increased risk of high-grade CIN in women with an hrHPV-positive normal baseline smear and a repeat normal smear at 6 months.
  
  
  CONCLUSIONS
  HrHPV-positive women without type 16, 18, 31, or 33 had a relatively low risk of high-grade CIN. Among women with baseline normal cytology and among women with a baseline and repeat normal smear, HPV16/18-positive women showed an increased risk of high-grade CIN. This warrants more aggressive management of HPV16/18-positive women compared with other hrHPV-positive women.
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, Vrije University Medical Center, Amsterdam, the Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: Berkhof
authors.forename: Nicole W J
authors.initials: NW
authors.lastname: Bulkmans
authors.forename: Maaike C G
authors.initials: MC
authors.lastname: Bleeker
authors.forename: Saskia
authors.initials: S
authors.lastname: Bulk
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Snijders
authors.forename: Feja J
authors.initials: FJ
authors.lastname: Voorhorst
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
mesh_terms: D000328:Adult; D015331:Cohort Studies; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D008403:Mass Screening; D008875:Middle Aged; D009426:Netherlands; D027383:Papillomaviridae / Q000145:classification / Q000472:pathogenicity*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000821:virology; D012307:Risk Factors; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000821:virology; D014626:Vaginal Smears
chemical_list: D004279:DNA, Viral