Human papillomavirus type-specific 18-month risk of high-grade cervical intraepithelial neoplasia in women with a normal or borderline/mildly dyskaryotic smear

Johannes Berkhof, Nicole W J Bulkmans, Maaike C G Bleeker, Saskia Bulk, Peter J F Snijders, Feja J Voorhorst, Chris J L M Meijer

Research output: Contribution to journalArticleAcademicpeer-review

65 Citations (Scopus)


INTRODUCTION: 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.

MATERIALS AND 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.

DISCUSSION: 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.

Original languageEnglish
Pages (from-to)1268-73
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Issue number7
Publication statusPublished - Jul 2006


  • Adult
  • Cervical Intraepithelial Neoplasia
  • Cohort Studies
  • Comparative Study
  • DNA, Viral
  • Female
  • Humans
  • Journal Article
  • Mass Screening
  • Middle Aged
  • Netherlands
  • Papillomaviridae
  • Papillomavirus Infections
  • Research Support, Non-U.S. Gov't
  • Risk Factors
  • Uterine Cervical Dysplasia
  • Uterine Cervical Neoplasms
  • Vaginal Smears

Cite this