International Journal of Cancer Early View (Articles online in advance of print) Published Online: 3 Apr 2006 Copyright © 2006 Wiley-Liss, Inc., A Wiley Company Early Detection and Diagnosis Overview of the European and North American studies on HPV testing in primary cervical cancer screening Jack Cuzick 1 * , Christine Clavel 2 , Karl-Ulrich Petry 3 , Chris J.L.M. Meijer 4 , Heike Hoyer 5 , Samuel Ratnam 6 , Anne Szarewski 1 , Philippe Birembaut 2 , Shalini Kulasingam 7 , Peter Sasieni 1 , Thomas Iftner 8 1 Cancer Research UK, Wolfson Institute of Preventive Medicine, London, United Kingdom 2 Laboratoire Pol Bouin, C.H.U. de Reims, Reims, France 3 Abteilung für Gynäkologische Onkologie MHH, Hannover, Germany 4 Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands 5 Institute of Medical Statistics, Friedrich Schiller University, Jena, Germany 6 Public Health Laboratory, Memorial University, St. John's, NL, Canada 7 Department of Obstetrics and Gynecology, Duke University, Durham, NC, USA 8 Experimentelle Virologie, Universitaets-klinikum Tuebingen, Tuebingen, Germany email: Jack Cuzick (jack.cuzick@cancer.org.uk ) * Correspondence to Jack Cuzick, Cancer Research UK, Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, Queen Mary School of Medicine, Charterhouse Square, London EC1M 6BQ, UK Fax: +40-20-7014-0269. Funded by: EC-grant; Grant Number: QLG4-CJ-2000-1238-HPVCCS KEYWORDS HPV testing  cervical screening  sensitivity  specificity  primary screening ABSTRACT Several studies suggest that HPV testing is more sensitive than cytology in primary cervical screening. These studies had different designs and were reported in different ways. Individual patient data were collected for all European and North American studies in which cytology was routinely performed and HPV testing was included as an additional parallel test. More than 60,000 women were included. The sensitivity and specificity of HPV testing were compared with routine cytology, both overall and for ages <35, 35-49 and 50+. The age-specific prevalence of high risk HPV (hr-HPV) was also analysed. HPV testing was substantially more sensitive in detecting CIN2+ than cytology (96.1% vs. 53.0%) but less specific (90.7% vs. 96.3%). The sensitivity of HPV testing was similar in all studies carried out in different areas of Europe and North America, whereas the sensitivity of cytology was highly variable. HPV sensitivity was uniformly high at all ages, whereas the sensitivity of cytology was substantially better in women over the age of 50 than in younger women (79.3% vs. 59.6%). The specificity of both tests increased with age. Positivity rates for HPV testing in women without high-grade CIN were region dependent. These results support the use of HPV testing as the sole primary screening test, with cytology reserved for women who test HPV positive. Large demonstration projects are needed to fully evaluate this strategy. © 2006 Wiley-Liss, Inc. Received: 21 October 2005; Accepted: 1 February 2006 DIGITAL OBJECT IDENTIFIER (DOI) 10.1002/ijc.21955 About DOI ARTICLE TEXT Currently in Europe and North America, cervical cancer screening is based on exfoliative cytology performed at intervals ranging between 1 and 5 years. Although there has been a marked reduction in incidence and mortality