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High-risk HPV may indicate cytologically false negative smears. An analysis of "normal" smears preceding CIN2/3
  1. Saskia Bulk (s.bulk{at}
  1. VU University Medical Center, Netherlands
    1. Lawrence Rozendaal (l.rozendaal{at}
    1. VU University Medical Center, Netherlands
      1. Gilda D. Zielinski (gd.zielinski{at}
      1. VU University Medical Center, Netherlands
        1. Johannes Berkhof (h.berkhof{at}
        1. VU University Medical Center, Netherlands
          1. Nathalie C. Fransen Daalmeijer (n.fransendaalmeijer{at}
          1. VU University medical Center, Netherlands
            1. Peter J.F. Snijders (pjf.snijders{at}
            1. VU University Medical Center, Netherlands
              1. Folkert J. Van Kemenade (f.vkemenade{at}
              1. VU University Medical Center, Netherlands
                1. Chris J.L.M. Meijer (cjlm.meijer{at}
                1. VU University Medical Center, Netherlands


                  Aims:Cervical screening, currently performed by cervical cytology, depends for its success on the timely detection of malignant lesions. 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. In this study we determined to which extent 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 cytologic 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 to 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 both 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.

                  • Cervical Intra-epithelial Neoplasia
                  • HPV
                  • PALGA
                  • Screening

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