European guidelines for quality assurance in cervical cancer screening Second Edition Editors M Arbyn A Anttila J Jordan G Ronco U Schenck N Segnan H G Wiener A Herbert J Daniel (technical editor) L von Karsa This document has been prepared with financial support from the European Communities through the Europe Against Cancer Programme (European Cervical Cancer Screening Network) and the EU Public Health Programme (European Cancer Network) The views expressed in this document are those of the authors and not necessarily reflect the official position of the European Commission Neither the Commission nor any person acting on its behalf can be held responsible for any use that may be made of the information in this document Europe Direct is a service to help you find answers to your questions about the European Union Freephone number (*): 00 800 10 11 (*) Certain mobile telephone operators not allow access to 00 800 numbers or these calls may be billed More information on the European Union is available on the Internet (http://europa.eu) Cataloguing data can be found at the end of this publication Luxembourg: Office for Official Publications of the European Communities, 2008 ISBN 978-92-79-07698-5 © European Communities, 2008 Printed in Belgium Printed on white chlorine-free paper II European guidelines for quality assurance in cervical cancer screening – Second edition EDITORS Marc Arbyn Unit of Cancer Epidemiology, Department of Epidemiology Scientific Institute of Public Health Brussels, Belgium Ahti Anttila Mass Screening Registry, Finnish Cancer Registry Helsinki, Finland Joe Jordan Birmingham Women’s Hospital Birmingham, United Kingdom Guglielmo Ronco Unit of Cancer Epidemiology Centre for Cancer Epidemiology and Prevention (CPO Piemonte) Turin, Italy Ulrich Schenck Institute of Pathology, Technical University Munich, Germany Nereo Segnan Unit of cancer Epidemiology, Department of Oncology CPO Piemonte (Piedmont Centre for Cancer Prevention) and S Giovanni Hospital Turin, Italy Helene G Wiener Clinical Institute of Pathology, Medical University of Vienna Vienna, Austria Amanda Herbert Guy’s & St Thomas’ NHS Foundation Trust London, United Kingdom John Daniel International Agency for Research on Cancer Lyon, France Lawrence von Karsa European Cancer Network (ECN) Coordination Office Screening Quality Control Group International Agency for Research on Cancer Lyon, France European guidelines for quality assurance in cervical cancer screening – Second edition III Address for correspondence European Cancer Network (ECN) Coordination Office International Agency for Research on Cancer 150 cours Albert Thomas F-69372 Lyon cedex 08 / France IV European guidelines for quality assurance in cervical cancer screening – Second edition CONTRIBUTORS Contributors Charles Anthony, Center for Public Health and Preventive Medicine Ormylia, Greece Ahti Anttila, Mass Screening Registry, Finnish Cancer Registry Helsinki, Finland Marc Arbyn, Unit of Cancer Epidemiology, Department of Epidemiology, Scientific Institute of Public Health Brussels, Belgium Joan Austoker, Division of Public Health and Primary Health Care Oxford, United Kingdom Jean-Jacques Baldauf, Department of Obstetrics and Gynaecology, Hôpitaux Universitaires de Strasbourg Strasbourg, France Nikolaus Becker, German Cancer Research Centre Heidelberg, Germany Christine Bergeron, Laboratoire Pasteur Cerba Cergy-Pontoise, France Miklós Bodó, Semmelweis University, I Pathological Institute Budapest, Hungary Peter Boyle International Agency for Research on Cancer Lyon, France Johan Bulten, Institute of Pathology, Radboud University Nijmegen Medical Centre Nijmegen, The Netherlands Christine Clavel, Laboratoire Pol Bouin Reims, France John Daniel International Agency for Research on Cancer Lyon, France Philip Davies, European Cervical Cancer Association Lyon, France European guidelines for quality assurance in cervical cancer screening – Second edition V CONTRIBUTORS Santiago Dexeus, Instituto Dexeus Barcelona, Spain Joakim Dillner, Department of Medical Microbiology, Lund University Lund, Sweden Lajos Döbr ssy, Office of Chief Medical Officer Iklad, Hungary Muriel Fender, Association EVE Strasbourg, France Livia Giordano, CPO Piemonte Turin, Italy Matti Hakama, School of Public Health, University of Tampere Tampere, Finland Amanda Herbert, Guy’s & St Thomas’ NHS Foundation Trust London, United Kingdom Reinhard Horvat, Institute of Pathology Vienna, Austria Thomas Iftner, Institute of Medical Virology Tubingen, Germany Joe Jordan, Birmingham Women’s Hospital Birmingham, United Kingdom Lawrence von Karsa, European Cancer Network International Agency for Research on Cancer Lyon, France Paul Klinkhamer, PAMM Eindhoven, The Netherlands Markos Kyprianou European Commissioner for Health and Consumer Protection Elsebeth Lynge, Institute of Public Health, University of Copenhagen Copenhagen, Denmark Pierre Martin-Hirsch, Department of Obstetrics and Gynaecology, Royal Preston Hospital Preston, United Kingdom VI European guidelines for quality assurance in cervical cancer screening – Second edition CONTRIBUTORS Euphemia McGoogan, formerly Department of Pathology, University of Edinburgh Edinburgh, United Kingdom Anthony B Miller, Deutsches Krebsforschungzentrum Heidelberg, Germany Guillermo Domenech Muniz, Directorate General of Public Health Junta de Castilla y León, Spain Pekka Nieminen, Helsinki University Central Hospital Helsinki, Finland Sonia Pagliusi, formerly, Initiative for Vaccine Research, Vaccines and Biologicals, Family and Community Health, WHO Geneva, Switzerland Julietta Patnick, National Health System Cervical Cancer Screening Programme Sheffield, United Kingdom Walter Prendiville, Coombe Women’s Hospital Dublin, Ireland Odette Real, Centro de Oncologia de Coimbra Coimbra, Portugal Guglielmo Ronco, Unit of Cancer Epidemiology, CPO Piemonte Turin, Italy Amaya Hernandez Rubio, Directorate General of Public Health Junta de Castilla y León, Spain Peter Sasieni, Wolfson Institute of Preventive Medicine London, United Kingdom Ulrich Schenck, Institute of Pathology, Technical University Munich, Germany Nereo Segnan, Unit of cancer Epidemiology, Department of Oncology, CPO Piemonte and S Giovanni Hospital Turin, Italy Peter Stern, Paterson Institute for Cancer Research Manchester, United Kingdom Daniel Da Silva, Centro de Oncologia de Coimbra Coimbra, Portugal European guidelines for quality assurance in cervical cancer screening – Second edition VII CONTRIBUTORS Pär Sparen, Department of Medical Epidemiology and Biostatistics, Karolinska Institute Stockholm, Sweden Silvia Tejero Encinas, Regional Health Service – Hospital General Yagüe of Burgos Junta de Castilla y León, Spain Anne Szarewski, Imperial Cancer Fund London, United Kingdom Premila Webster, Division of Public Health and Primary Health Care Oxford, United Kingdom Elisabete Weiderpass, Norwegian Cancer Register Oslo, Norway Helene G Wiener, Clinical Institute of Pathology, Medical University of Vienna Vienna, Austria Maja Zakelj, Epidemiology and Cancer Registries, Institute of Oncology Ljubljana, Slovenia Conflicts of interest, declared by authors, contributors, editors or reviewers of chapters of the European Guidelines for Quality Assurance in Cervical Cancer Screening – Second Edition* M Arbyn has received travel grants from producers of HPV vaccines (Smith-Glaxo Kline and Sanofi Pharmaceuticals, Inc.) P Davies has served on the scientific advisory board of Roche Molecular Systems Inc., a diagnostic test manufacturer, prior to 2007 J Dillner is currently a consultant for and a recipient of research grants from a producer of HPV vaccines (Merck/SPMSD) T Iftner is an inventor of patents on a genotyping test ("Primer and probes for detection of papilloma-viruses", and "detection of human papillomaviruses") whereas the holder of the patents is either University Hospital Tuebingen or Greiner BioOne * Disclosed by experts concerned between August & November 2007 No other potential conflict of interest relevant to this publication was reported VIII European guidelines for quality assurance in cervical cancer screening – Second edition Prefaces HPV VACCINATION Addendum Important new evidence has become available since the preparation of the preceding review on HPV vaccination (Arbyn & Dillner, 2007) Furthermore, some statements in the review, if taken out of context, might be understood as general recommendations to implement HPV vaccination or testing policies or practices We would like to point out that testing of unsymptomatic women for prevention of cervical cancer is recommended in the current, second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening to take place only within organised screening programme settings Moreover, primary HPV testing for cervical cancer screening is currently only recommended in pilot studies (see chapters and 3) As a matter of editorial policy, the current Guideline edition does not provide recommendations on implementation of HPV vaccination Development of comprehensive European guidelines on prevention of cervical cancer which appropriately integrate screening and vaccination strategies is a key aim of the next phase of project activities supported by the EU Public Health Programme 1.1 Efficacy against HPV16/18-specific CIN2+ or AIS in women with current or prior HPV infection In May 2007, the 3-year follow-up results of the FUTURE I and FUTURE II phase-III trials were published (FUTURE II Study Group 2007; Garland et al., 2007) A major aim of these studies was to evaluate protection of prophylactic vaccination with Gardasil® against vaccine-type-related CIN2+, AIS, cervical cancers (FUTURE I and FUTURE II) and external anogenital lesions (FUTURE I) Prior exposure to vaccine HPV types was assessed by measuring the presence of type-specific antibodies at day and by testing for HPV DNA of vaccine types at day and at month after application of the last vaccine dose Excellent protection was observed at month 36 against HPV16/18-related CIN2+ lesions in HPVnaïve women who received all three vaccine doses according to the prescribed protocol: 100% (95% CI: 86-100%) for CIN2, 97% (95% CI: 79-100%) for CIN3, and 100% (95% CI: