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High-risk human papillomavirus is present in cytologically false-negative smears: an analysis of “normal” smears preceding CIN2/3
  1. S Bulk1,
  2. L Rozendaal1,
  3. G D Zielinski1,
  4. J Berkhof2,
  5. N C Fransen Daalmeijer1,
  6. P J F Snijders1,
  7. F J van Kemenade1,
  8. C J L M Meijer1
  1. 1
    Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
  2. 2
    Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
  1. ProfessorDr C J L M Meijer, Department of Pathology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands; cjlm.meijer{at}


Aims: Cervical screening, currently performed by cervical cytology, depends on the timely detection of malignant lesions for its success. The presence of high-risk human papillomavirus (hrHPV) is associated with an increased risk of subsequent high-grade cervical intra-epithelial neoplasia (CIN2/3) and cervical cancer. The aim of this study was to determine the extent to which hrHPV is present in cervical smears with a high a priori chance of being false negative (ie, in normal smears preceding CIN2/3).

Methods: Archival specimens of 187 women with CIN2/3 and preceding normal conventional smears were identified retrospectively. Of these specimens, 144 (77%) had adequate cytological samples for further HPV DNA testing.

Results: Of 144 CIN2/3 lesions, preceding normal smears showed hrHPV positivity in 80% of cases. Of the hrHPV-positive smears, 69% were upgraded cytologically at rescreening compared with 24% of hrHPV-negative smears (p<0.001). Upgrading of smears was not associated with specific hrHPV types (p = 0.217). In over 90% of cases, type concordance in smear and CIN2/3 lesion was demonstrated.

Conclusions: hrHPV is present in a high proportion of normal archival smears preceding CIN2/3, and false-negative cytology was highly associated with the presence of hrHPV. This supports the current notion that hrHPV testing can be used as a primary cervical screening tool. If so, hrHPV-positive cervical smears should be carefully examined for cytological abnormalities to reduce false-negative cervical cytology.

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  • Funding: This study was funded by grants 2200.0089 and 28-2831 from the Health Research and Development Council of The Netherlands (ZorgOnderzoek Nederland). The sponsor of the study had no role in study design, collection, analysis and interpretation of data or writing the report.

  • Competing interests:None declared.

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