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Human Papillomavirus 16 E6 Antibodies in Individuals without Diagnosed Cancer: A Pooled Analysis

Lang Kuhs KA 1 , Anantharaman D 2 , Waterboer T 3 , Johansson M 2 , Brennan P 2 , Michel A 3 Show all authors , Willhauck-Fleckenstein M 3 , Purdue MP 4 , Holcátová I 5 , Ahrens W 6 , Lagiou P 7 , Polesel J 8 , Simonato L 9 , Merletti F 10 , Healy CM 11 , Kjaerheim K 12 , Conway DI 13 , Macfarlane TV 14 , Thomson P 15 , Castellsagué X 16 , Znaor A 17 , Black A 18 , Huang WY 18 , Krogh V 19 , Trichopoulou A 20 , Bueno-de-Mesquita HB 21 , Clavel-Chapelon F 22 , Weiderpass E 23 , Ekström J 24 , Riboli E 25 , Tjønneland A 26 , Sánchez MJ 27 , Travis RC 28 , Hildesheim A 18 , Pawlita M 3 , Kreimer AR 18

Affiliations 

  • 1 National Cancer Institute, NIH, Bethesda, Maryland. Krystle.Kuhs@nih.gov
  • 2 International Agency for Research on Cancer (IARC), Lyon, France
  • 3 German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 4 National Cancer Institute, NIH, Bethesda, Maryland. Ontario Institute for Cancer Research, Toronto, Ontario, Canada
  • 5 Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic
  • 6 Leibniz Institute for Prevention Research and Epidemiology, Bremen, Germany
  • 7 University of Athens Medical School, Athens, Greece
  • 8 CRO Aviano National Cancer Institute, Aviano, Italy
  • 9 Laboratory of Public Health and Population Studies, Department of Molecular Medicine, University of Padova, Padova, Italy
  • 10 Department of Medical Sciences, University of Turin, Turin, Italy
  • 11 Trinity College School of Dental Science, Dublin, Ireland
  • 12 Department of Research, Cancer Registry of Norway, Oslo, Norway
  • 13 University of Glasgow, Glasgow, United Kingdom. University of Aberdeen, Aberdeen, United Kingdom
  • 14 University of Aberdeen, Aberdeen, United Kingdom
  • 15 University of Newcastle on Tyne, Newcastle, United Kingdom
  • 16 Unit of Infections and Cancer, Institut Català d'Oncologia (ICO), IDIBELL, CIBERESP, L'Hospitalet de Llobregat, Catalonia, Spain
  • 17 Croatian National Institute of Public Health, Zagreb, Croatia
  • 18 National Cancer Institute, NIH, Bethesda, Maryland
  • 19 Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • 20 Hellenic Health Foundation, Athens, Greece. Academy of Athens, Athens, Greece. University of Athens Medical School, Athens, Greece
  • 21 National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. University Medical Centre, Utrecht, the Netherlands. The School of Public Health, Imperial College London, London, United Kingdom. University of Malaya, Kuala Lumpur, Malaysia
  • 22 Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France. Université Paris Sud, Villejuif, France. Institut Gustave Roussy, Villejuif, France
  • 23 Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland
  • 24 Department of Clinical Sciences, Lund University, Lund, Sweden
  • 25 Imperial College London, London, United Kingdom
  • 26 Danish Cancer Society Research Center, Copenhagen, Denmark
  • 27 Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
  • 28 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
Cancer Epidemiol Biomarkers Prev, 2015 Apr;24(4):683-9.
PMID: 25623733 DOI: 10.1158/1055-9965.EPI-14-1217

Abstract

BACKGROUND: The increasing incidence of oropharyngeal cancer in many developed countries has been attributed to human papillomavirus type 16 (HPV16) infections. Recently, HPV16 E6 serology has been identified as a promising early marker for oropharyngeal cancer. Therefore, characterization of HPV16 E6 seropositivity among individuals without cancer is warranted.

METHODS: A total of 4,666 controls were pooled from several studies of cancer and HPV seropositivity, all tested within the same laboratory. HPV16 E6 seropositive controls were classified as having (i) moderate [mean fluorescent intensity (MFI) ≥ 484 and <1,000] or (ii) high seroreactivity (MFI ≥ 1,000). Associations of moderate and high HPV16 E6 seroreactivity with (i) demographic risk factors; and seropositivity for (ii) other HPV16 proteins (E1, E2, E4, E7, and L1), and (iii) E6 proteins from non-HPV16 types (HPV6, 11, 18, 31, 33, 45, and 52) were evaluated.

RESULTS: Thirty-two (0.7%) HPV16 E6 seropositive controls were identified; 17 (0.4%) with moderate and 15 (0.3%) with high seroreactivity. High HPV16 E6 seroreactivity was associated with former smoking [odds ratio (OR), 5.5; 95% confidence interval (CI), 1.2-51.8], and seropositivity against HPV16 L1 (OR, 4.8; 95% CI, 1.3-15.4); E2 (OR, 7.7; 95% CI, 1.4-29.1); multiple HPV16 proteins (OR, 25.3; 95% CI, 2.6-119.6 for three HPV16 proteins beside E6) and HPV33 E6 (OR, 17.7; 95% CI, 1.9-81.8). No associations were observed with moderate HPV16 E6 seroreactivity.

CONCLUSIONS: High HPV16 E6 seroreactivity is rare among individuals without diagnosed cancer and was not explained by demographic factors.

IMPACT: Some HPV16 E6 seropositive individuals without diagnosed HPV-driven cancer, especially those with seropositivity against other HPV16 proteins, may harbor a biologically relevant HPV16 infection.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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