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High-risk human papillomavirus is present in cytologically false-negative smears: an analysis of "normal" smears preceding CIN2/3

¹ Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
² Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands

Correspondence to:
ProfessorDr C J L M Meijer, Department of Pathology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands; cjlm.meijer{at}vumc.nl

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.