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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Research Article

Cervical Cancer Screening: Comparison of conventional Pap smear test, liquid-based cytology and human papillomavirus testing as stand-alone or co-testing strategies

Linda A Liang, Thomas Einzmann, Arno Franzen, Katja Schwarzer, Gunther Schauberger, Dirk Schriefer, Kathrin Radde, Sylke R Zeissig, Hans Ikenberg, Chris JLM Meijer, Charles J Kirkpatrick, Heinz Kölbl, Maria Blettner and Stefanie J Klug
Linda A Liang
1Epidemiology, Department of Sport and Health Sciences, Technical University Munich
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Thomas Einzmann
2Department of Obstetrics and Gynecology, University Hospital Cologne
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Arno Franzen
3Department of Obstetrics and Gynecology, Gemeinschaftsklinikum Mittelrhein
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Katja Schwarzer
4VivaQ MVZ Mainz GmbH
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Gunther Schauberger
1Epidemiology, Department of Sport and Health Sciences, Technical University Munich
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Dirk Schriefer
5Center of Clinical Neuroscience, University Hospital Carl Gustav Carus Dresden
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Kathrin Radde
1Epidemiology, Department of Sport and Health Sciences, Technical University Munich
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Sylke R Zeissig
6Cancer Registry of Rhineland-Palatinate
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Hans Ikenberg
7Cytomol MVZ
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Chris JLM Meijer
8Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam
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Charles J Kirkpatrick
9Institute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz
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Heinz Kölbl
10Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna
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Maria Blettner
11Institut für Medizinische Biometrie Epidemiologie und Informatik, Johannes Gutenberg Universität
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Stefanie J Klug
1Epidemiology, Department of Sport and Health Sciences, Technical University Munich
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  • For correspondence: stefanie.klug@tum.de
DOI: 10.1158/1055-9965.EPI-20-1003
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Abstract

Background:Some countries have implemented stand-alone Human Papillomavirus (HPV) testing while others consider co-testing for cervical cancer screening. We compared both strategies within a population-based study. Methods:The MARZY cohort study was conducted in Germany. Randomly selected women from population registries aged ≥30 years (n=5275) were invited to screening with Pap smear, liquid-based cytology (LBC, ThinPrep®) and HPV testing (Hybrid Capture®2, HC2). Screen positive participants (ASC-US+ or high-risk HC2 (hrHC2)) and a random 5% sample of screen negatives were referred to colposcopy. Post hoc HPV genotyping was conducted by GP5+/6+ PCR-EIA with reverse line blotting. Sensitivity, specificity (adjusted for verification bias) and potential harms including number of colposcopies needed to detect 1 precancerous lesion (NNC) were calculated. Results:In 2627 screened women, cytological sensitivities (Pap, LBC: 47%) were lower than HC2 (95%) and PCR (79%) for CIN2+. Co-testing demonstrated higher sensitivities (HC2 co-testing: 99%; PCR co-testing: 84%), but at the cost of lower specificities (92%-95%) compared to HPV stand-alone (HC2: 95%; PCR: 94%) and cytology (97% or 99%). Co-testing versus HPV stand-alone showed equivalent relative sensitivity (HC2: 1.06, 95% CI 1.00-1.21; PCR: 1.07, 95% 1.00-1.27). Relative specificity of Pap co-testing with either HPV test was inferior to stand-alone HPV. LBC co-testing demonstrated equivalent specificity (both tests: 0.99, 95% CI 0.99-1.00). NNC was highest for Pap co-testing. Conclusions:Co-testing offers no benefit in detection over stand-alone HPV testing resulting in more false positive results and colposcopy referrals. Impact:HPV stand-alone screening offers a better balance of benefits and harms than co-testing.

  • Received July 9, 2020.
  • Revision received September 17, 2020.
  • Accepted November 2, 2020.
  • Copyright ©2020, American Association for Cancer Research.

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This OnlineFirst version was published on November 13, 2020
doi: 10.1158/1055-9965.EPI-20-1003

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Cervical Cancer Screening: Comparison of conventional Pap smear test, liquid-based cytology and human papillomavirus testing as stand-alone or co-testing strategies
Linda A Liang, Thomas Einzmann, Arno Franzen, Katja Schwarzer, Gunther Schauberger, Dirk Schriefer, Kathrin Radde, Sylke R Zeissig, Hans Ikenberg, Chris JLM Meijer, Charles J Kirkpatrick, Heinz Kölbl, Maria Blettner and Stefanie J Klug
Cancer Epidemiol Biomarkers Prev November 13 2020 DOI: 10.1158/1055-9965.EPI-20-1003

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Cervical Cancer Screening: Comparison of conventional Pap smear test, liquid-based cytology and human papillomavirus testing as stand-alone or co-testing strategies
Linda A Liang, Thomas Einzmann, Arno Franzen, Katja Schwarzer, Gunther Schauberger, Dirk Schriefer, Kathrin Radde, Sylke R Zeissig, Hans Ikenberg, Chris JLM Meijer, Charles J Kirkpatrick, Heinz Kölbl, Maria Blettner and Stefanie J Klug
Cancer Epidemiol Biomarkers Prev November 13 2020 DOI: 10.1158/1055-9965.EPI-20-1003
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