Objectives: We aimed to analyze the false-negative (FN) liquid-based cytology diagnoses from the 5 years preceding all the 2013 histologically proven cervical intraepithelial neoplasia (CIN)2-3 and squamous cell carcinoma (SCC) and to propose corrective actions. Study Design: This was a retrospective, blinded rescreening (‘5-year look-back') of liquid-based cytology samples with negative categorizations, which occurred before histologically proven CIN2-3 and SCC. Results: The FN rate was 7.8% (21/256 samples preceding CIN2-3 and 0/13 samples preceding SCC). Slides confirmed as ‘negative', ‘interpretation error' and ‘screening error', respectively, were 3.3% (9/269), 2.6% (7/269) and 1.9% (5/269). In 9/12 cases, error was associated with small atypical cells. In 7/12 cases, these diagnostic cells were less than 5/10 HPF. Inflammation and prominent reactive changes were present in 5/12 cases. Five patients had a positive clinical history. In 2 cases, there were multiple-cell-layer artifacts. Dense groups of small blue atypical cells were missed in 2 other cases. Dotting was imprecise in 6/7 samples. Conclusion: Considering the above results, we specifically reoriented our continuous education activities, focusing rapid rescreening on scanty, isolated, small, atypical cells and dense cell groups. Prior to final diagnosis, pathologists should systematically review the entire surface of the dotted slides, with special attention being devoted to slides with multiple cell layers and tridimensional groups.

Keywords:
Cervical cytology, SurePath, Cytological-histological correlations, False-negative diagnoses
1.
Wiener HG, Klinkhamer P, Schenck U, Arbyn M, Bulten J, Bergeron C, Herbert A: European guidelines for quality assurance in cervical cancer screening: recommendations for cytology laboratories. Cytopathology 2007;18:67-78.
2.
Bulten J, Horvat R, Jordan J, Herbert A, Wiener H, Arbyn M: European guidelines for quality assurance in cervical histopathology. Acta Oncol 2011;50:611-620.
3.
Raab SS, Jones BA, Souers R, Tworek JA: The effect of continuous monitoring of cytologic-histologic correlation data on cervical cancer screening performance. Arch Pathol Lab Med 2008;132:16-22.
4.
Jones BA, Novis DA: Cervical biopsy-cytology correlation. A College of American Pathologists Q-Probes study of 22,439 correlations in 348 laboratories. Arch Pathol Lab Med 1996;120:523-531.
5.
Crothers BA, Jones BA, Cahill LA, Moriarty AT, Mody DR, Tench WD, Souers RJ: Quality improvement opportunities in gynecologic cytologic-histologic correlations: findings from the College of American Pathologists Gynecologic Cytopathology Quality Consensus Conference Working Group 4. Arch Pathol Lab Med 2013;137:199-213.
6.
Arbyn M, Anttila A, Jordan J, Ronco G, Schenck U, Segnan N, Wiener H, Herbert A, von Karsa L: European guidelines for quality assurance in cervical cancer screening, ed 2: summary document. Ann Oncol 2010;21:448-458.
7.
Bowditch RC, Clarke JM, Baird PJ, Greenberg ML: Results of an Australian trial using SurePath liquid-based cervical cytology with FocalPoint computer-assisted screening technology. Diagn Cytopathol 2012;40:1093-1099.
8.
Arbyn M, Herbert A, Schenck U, Nieminen P, Jordan J, McGoogan E, Patnick J, Bergeron C, Baldauf JJ, et al: European guidelines for quality assurance in cervical cancer screening: recommendations for collecting samples for conventional and liquid-based cytology. Cytopathology 2007;18:133-139.
9.
Solomon D, Nayar R (ed): The Bethesda System for Reporting Cervical Cytology. Definitions, Criteria and Explanatory Notes, ed 2. New York, Springer 2004.
10.
Herbert A, Bergeron C, Wiener H, Schenck U, Klinkhamer PJ, Arbyn M: European guidelines for quality assurance in cervical cancer screening: recommendations for cervical cytology terminology. Cytopathology 2007;18:213-219.
11.
Department of Health and Human Services Health Care Financing Administration: Clinical Laboratory Improvement Amendments of 1998 Standard: Cytology. Federal Register, 1992.
12.
Jones BA: Rescreening in gynecologic cytology. Rescreening of 3,762 previous cases for current high-grade squamous intraepithelial lesions and carcinoma - a College of American Pathologists Q-Probes study of 312 institutions. Arch Pathol Lab Med 1995;119:1097-1103.
13.
Allen KA, Zaleski S, Cohen MB: Review of negative Papanicolaou tests. Is the retrospective 5-year review necessary? Am J Clin Pathol 1994;101:19-21.
14.
Gatscha, RM, Warren GP, Saigo PE: Quality assurance: insight into a laboratory's performance. Lab Med 1994;25:258.
15.
Hatem F, Wilbur DC: High-grade squamous cervical lesions following negative Papanicolaou smears: false-negative cervical cytology or rapid progression. Diagn Cytopathol 1995;12:135-141.
16.
Tabbara SO, Sidawy MK: Evaluation of the 5-year review of negative cervical smears in patients with high-grade squamous intraepithelial lesions. Diagn Cytopathol 1996;15:7-10;disc 10-11.
17.
Montes MA, Cibas ES, DiNisco SA, Lee KR: Cytologic characteristics of abnormal cells in prior ‘normal' cervical/vaginal Papanicolaou smears from women with a high-grade squamous intraepithelial lesion. Cancer 1999;87:56-59.
18.
Nick TG, Bush DF, Cason Z, Lemos LB: Review of negative PAP smears: quality assurance protocol for high-grade squamous intraepithelial lesions. Acta Cytol 1995;39-90.
19.
Cibas ES: Laboratory management; in Cibas ES, Ducatman BS (eds): Cytology Diagnostic Principles and Clinical Correlates. Philadelphia, Saunders Elsevier, 2009, pp 495-522.
20.
Schlecht NF, Platt RW, Duarte-Franco E, et al: Human papillomavirus infection and time to progression and regression of cervical intraepithelial neoplasia. J Natl Cancer Inst 2003;95:1336-1343.
21.
Stoler MH, Mills SE, Gersell DJ, Walker AN: Small-cell neuroendocrine carcinoma of the cervix. A human papillomavirus type 18-associated cancer. Am J Surg Pathol 1991;15:28-32.
22.
Kurman RJ, Schiffman MH, Lancaster WD, Reid R, Jenson AB, Temple GF, Lorincz AT: Analysis of individual human papillomavirus types in cervical neoplasia: a possible role for type 18 in rapid progression. Am J Obstet Gynecol 1988;159:293-296.
23.
Dehner LP: Cervicovaginal cytology, false-negative results, and standards of practice. Am J Clin Pathol 1993;99:45-47.
24.
College of American Pathologists: Surveys 2013: PAP Gynecologic Cytology PT & Educational Programs. Year-End Summary Report. Northfield, CAP, 2013.
25.
Gupta N, John D, Dudding N, Crossley J, Smith JH: Factors contributing to false-negative and potential false-negative cytology reports in SurePath™ liquid-based cervical cytology. Cytopathology 2013;24:39-43.
26.
Croll E, Rana DN, Walton LJ: Hyperchromatic crowded cell groups in gynaecological liquid-based cytology samples. Br J Biomed Sci 2010;67:154-163; quiz 165.
27.
Faraker CA, Boxer ME: Rapid review (partial rescreening) of cervical cytology. Four years experience and quality assurance implications. J Clin Pathol 1996;49:587-591.
28.
Arbyn M, Schenck U: Detection of false-negative Pap smears by rapid reviewing. A meta-analysis. Acta Cytol 2000;44:949-957.
29.
Arbyn M, Schenck U, Ellison E, Hanselaar A: Metaanalysis of the accuracy of rapid prescreening relative to full screening of Pap smears. Cancer Cytopathol 2003;99:9-16.
30.
Arbyn M, Ronco G, Anttila A, Meijer CJLM, Poljak M, Ogilvie G, Koliopoulos G, Naucler P, Sankaranarayanan R, et al: Evidence regarding HPV testing in secondary prevention of cervical cancer. Vaccine 2012;30(suppl 5):F88-F99.
31.
Ronco G, Dillner J, Elfström KM, Tunesi S, Snijders PJ, Arbyn M, Kitchener H, Segnan N, Gilham C, Giorgi-Rossi P, Berkhof J, Peto J, Meijer CJ; International HPV screening working group: Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet 2014;383:524-532.
© 2015 S. Karger AG, Basel
2015
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.