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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Research Articles

Attribution of 12 High-Risk Human Papillomavirus Genotypes to Infection and Cervical Disease

Elmar A. Joura, Kevin A. Ault, F. Xavier Bosch, Darron Brown, Jack Cuzick, Daron Ferris, Suzanne M. Garland, Anna R. Giuliano, Mauricio Hernandez-Avila, Warner Huh, Ole-Erik Iversen, Susanne K. Kjaer, Joaquin Luna, Dianne Miller, Joseph Monsonego, Nubia Munoz, Evan Myers, Jorma Paavonen, Punnee Pitisuttithum, Marc Steben, Cosette M. Wheeler, Gonzalo Perez, Alfred Saah, Alain Luxembourg, Heather L. Sings and Christine Velicer
Elmar A. Joura
1Department of Gynecology and Obstetrics, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
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  • For correspondence: elmar.joura@meduniwien.ac.at
Kevin A. Ault
2Department of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, Kansas.
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F. Xavier Bosch
3Institut Catala d'Oncologia, IDIBELL, Barcelona, Spain.
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Darron Brown
4Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
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Jack Cuzick
5Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom.
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Daron Ferris
6Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia.
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Suzanne M. Garland
7Department of Microbiology Infectious Diseases, The Royal Women's Hospital, Department of Obstetrics and Gynaecology, University of Melbourne, Australia.
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Anna R. Giuliano
8Center for Infection Research in Cancer (CIRC), Moffitt Cancer Center, Tampa, Florida.
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Mauricio Hernandez-Avila
9National Institute of Public Health, Cuernavaca, Morelos, Mexico.
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Warner Huh
10Division of Gynecologic Oncology, University of Alabama, Birmingham, Alabama.
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Ole-Erik Iversen
11Institute of Clinical Medicine, University of Bergen/Haukeland University Hospital, Bergen, Norway.
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Susanne K. Kjaer
12Danish Cancer Society Research Center, Copenhagen, Denmark and Department of Gynecology, Rigshospitalet, University of Copenhagen, Denmark.
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Joaquin Luna
13Department of Obstetrics and Gynecology, Clinica Colsanitas, Fundacion Universitaria Sanitas, Bogota, Colombia.
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Dianne Miller
14Department of Obstetrics and Gynaecology, University of British Colombia, Vancouver, Canada.
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Joseph Monsonego
15Institut du col, Paris, France.
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Nubia Munoz
16National Institute of Cancer, Bogotá, Colombia.
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Evan Myers
17Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina.
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Jorma Paavonen
18Department of Obstetrics and Gynecology, University Central Hospital, Helsinki, Finland.
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Punnee Pitisuttithum
19Faculty of Tropical Medicine, Mahidol University, Thailand.
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Marc Steben
20Direction des Risques Biologiques et de la Santé au travail, Institut National de Santé Publique du Québec, Montréal, Quebec, Canada.
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Cosette M. Wheeler
21Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
22Department of Obstetrics and Gynecology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
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Gonzalo Perez
23Merck & Co., Inc., Whitehouse Station, New Jersey.
24Universidad del Rosario, Bogota, Colombia.
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Alfred Saah
23Merck & Co., Inc., Whitehouse Station, New Jersey.
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Alain Luxembourg
23Merck & Co., Inc., Whitehouse Station, New Jersey.
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Heather L. Sings
23Merck & Co., Inc., Whitehouse Station, New Jersey.
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Christine Velicer
23Merck & Co., Inc., Whitehouse Station, New Jersey.
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DOI: 10.1158/1055-9965.EPI-14-0410 Published October 2014
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Abstract

Background: We estimated the prevalence and incidence of 14 human papillomavirus (HPV) types (6/11/16/18/31/33/35/39/45/51/52/56/58/59) in cervicovaginal swabs, and the attribution of these HPV types in cervical intraepithelial neoplasia (CIN), and adenocarcinoma in situ (AIS), using predefined algorithms that adjusted for multiple-type infected lesions.

Methods: A total of 10,656 women ages 15 to 26 years and 1,858 women ages 24 to 45 years were enrolled in the placebo arms of one of three clinical trials of a quadrivalent HPV vaccine. We estimated the cumulative incidence of persistent infection and the proportion of CIN/AIS attributable to individual carcinogenic HPV genotypes, as well as the proportion of CIN/AIS lesions potentially preventable by a prophylactic 9-valent HPV6/11/16/18/31/33/45/52/58 vaccine.

Results: The cumulative incidence of persistent infection with ≥1 of the seven high-risk types included in the 9-valent vaccine was 29%, 12%, and 6% for women ages 15 to 26, 24 to 34, and 35 to 45 years, respectively. A total of 2,507 lesions were diagnosed as CIN or AIS by an expert pathology panel. After adjusting for multiple-type infected lesions, among women ages 15 to 45 years, these seven high-risk types were attributed to 43% to 55% of CIN1, 70% to 78% of CIN2, 85% to 91% of CIN3, and 95% to 100% of AIS lesions, respectively. The other tested types (HPV35/39/51/56/59) were attributed to 23% to 30% of CIN1, 7% to 14% of CIN2, 3% to 4% of CIN3, and 0% of AIS lesions, respectively.

Conclusions: Approximately 85% or more of CIN3/AIS, >70% CIN2, and approximately 50% of CIN1 lesions worldwide are attributed to HPV6/11/16/18/31/33/45/52/58.

Impact: If 9-valent HPV vaccination programs are effectively implemented, the majority of CIN2 and CIN3 lesions worldwide could be prevented, in addition to approximately one-half of CIN1. Cancer Epidemiol Biomarkers Prev; 23(10); 1997–2008. ©2014 AACR.

This article is featured in Highlights of This Issue, p. 1957

Footnotes

  • Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).

  • Received April 23, 2014.
  • Revision received June 19, 2014.
  • Accepted July 13, 2014.
  • ©2014 American Association for Cancer Research.
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Cancer Epidemiology Biomarkers & Prevention: 23 (10)
October 2014
Volume 23, Issue 10
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Attribution of 12 High-Risk Human Papillomavirus Genotypes to Infection and Cervical Disease
Elmar A. Joura, Kevin A. Ault, F. Xavier Bosch, Darron Brown, Jack Cuzick, Daron Ferris, Suzanne M. Garland, Anna R. Giuliano, Mauricio Hernandez-Avila, Warner Huh, Ole-Erik Iversen, Susanne K. Kjaer, Joaquin Luna, Dianne Miller, Joseph Monsonego, Nubia Munoz, Evan Myers, Jorma Paavonen, Punnee Pitisuttithum, Marc Steben, Cosette M. Wheeler, Gonzalo Perez, Alfred Saah, Alain Luxembourg, Heather L. Sings and Christine Velicer
Cancer Epidemiol Biomarkers Prev October 1 2014 (23) (10) 1997-2008; DOI: 10.1158/1055-9965.EPI-14-0410

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Attribution of 12 High-Risk Human Papillomavirus Genotypes to Infection and Cervical Disease
Elmar A. Joura, Kevin A. Ault, F. Xavier Bosch, Darron Brown, Jack Cuzick, Daron Ferris, Suzanne M. Garland, Anna R. Giuliano, Mauricio Hernandez-Avila, Warner Huh, Ole-Erik Iversen, Susanne K. Kjaer, Joaquin Luna, Dianne Miller, Joseph Monsonego, Nubia Munoz, Evan Myers, Jorma Paavonen, Punnee Pitisuttithum, Marc Steben, Cosette M. Wheeler, Gonzalo Perez, Alfred Saah, Alain Luxembourg, Heather L. Sings and Christine Velicer
Cancer Epidemiol Biomarkers Prev October 1 2014 (23) (10) 1997-2008; DOI: 10.1158/1055-9965.EPI-14-0410
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