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Petry, KU; Schmidt, D; Scherbring, S; Luyten, A; Reinecke-Lüthge, A; Bergeron, C; Kommoss, F; Löning, T; Ordi, J; Regauer, S; Ridder, R.
Triaging Pap cytology negative, HPV positive cervical cancer screening results with p16/Ki-67 Dual-stained cytology.
Gynecol Oncol. 2011; 121(3):505-509
Doi: 10.1016/j.ygyno.2011.02.033
Web of Science
PubMed
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- Co-authors Med Uni Graz
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Regauer Sigrid
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Testing for human papillomavirus (HPV) has been shown to increase the sensitivity and negative predictive value for detection of high-grade cervical intraepithelial neoplasia (CIN2+), either when used in conjunction with Pap cytology testing or alone. However, there is no satisfying clinical management algorithm for women testing Pap negative/HPV positive. We therefore evaluated the clinical utility of a novel dual biomarker-based approach (p16/Ki-67 Dual-stained cytology) for the identification of CIN2+ in women with Pap negative/HPV positive screening results, without the need to refer all women to immediate colposcopy.
All women aged ≥30 enrolled during 2007/2008 into a regional prospective Pap/HPV co-testing screening pilot project and tested Pap negative, but positive for HPV (n=425) were included in the analysis. p16/Ki-67 Dual-stained cytology was performed from residual cellular material available from the liquid-based cytology vial collected during the initial Pap/HPV co-testing screening visit. Results were correlated to the presence of CIN2+ confirmed during preliminary follow-up.
p16/Ki-67 Dual-stained cytology tested positive at baseline in 108 out of 425 (25.4%) Pap negative/HPV positive cases. Sensitivity of Dual-stain testing for the detection of biopsy-confirmed CIN2+ during preliminary follow-up within the group of Pap negative/HPV positive women was 91.9% for CIN2+ (34/37 cases), and 96.4% for CIN3+ (27/28 cases). Specificity was 82.1% for CIN2+ on biopsy, and 76.9% for CIN3+, respectively.
Triaging Pap negative/HPV positive screening test results with p16/Ki-67 Dual-stained cytology may identify women with a high probability of underlying CIN2+ and may efficiently complement HPV-based screening programs to prevent cervical cancer.
Copyright © 2011 Elsevier Inc. All rights reserved.
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Cervical Intraepithelial Neoplasia - metabolism
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Cervical Intraepithelial Neoplasia - pathology
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Cervical Intraepithelial Neoplasia - virology
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Cohort Studies -
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Cyclin-Dependent Kinase Inhibitor p16 -
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Ki-67 Antigen - metabolism
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Staining and Labeling - methods
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Pap cytology
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Human papillomavirus, HPV
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p16(INK4a)
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Ki-67
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Dual-stained cytology
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Cervical intraepithelial neoplasia