title: Human Papillomavirus 16 E6 Antibodies in Individuals without Diagnosed Cancer: A Pooled Analysis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Cancer Institute, NIH, Bethesda, Maryland. Krystle.Kuhs@nih.gov.
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authors.lastname: Lang Kuhs
authors.affiliation: International Agency for Research on Cancer (IARC), Lyon, France.
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authors.lastname: Anantharaman
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany.
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authors.affiliation: International Agency for Research on Cancer (IARC), Lyon, France.
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authors.affiliation: International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: Paul
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authors.lastname: Brennan
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Angelika
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authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Martina
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authors.affiliation: National Cancer Institute, NIH, Bethesda, Maryland. Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
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authors.lastname: Purdue
authors.affiliation: Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic.
authors.forename: Ivana
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authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology, Bremen, Germany.
authors.forename: Wolfgang
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authors.lastname: Ahrens
authors.affiliation: University of Athens Medical School, Athens, Greece.
authors.forename: Pagona
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authors.lastname: Lagiou
authors.affiliation: CRO Aviano National Cancer Institute, Aviano, Italy.
authors.forename: Jerry
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authors.lastname: Polesel
authors.affiliation: Laboratory of Public Health and Population Studies, Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Lorenzo
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authors.lastname: Simonato
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
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authors.affiliation: Trinity College School of Dental Science, Dublin, Ireland.
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authors.affiliation: Department of Research, Cancer Registry of Norway, Oslo, Norway.
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authors.lastname: Kjaerheim
authors.affiliation: University of Glasgow, Glasgow, United Kingdom. University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: David I
authors.initials: DI
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authors.affiliation: University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Tatiana V
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authors.lastname: Macfarlane
authors.affiliation: University of Newcastle on Tyne, Newcastle, United Kingdom.
authors.forename: Peter
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authors.affiliation: Unit of Infections and Cancer, Institut Català d'Oncologia (ICO), IDIBELL, CIBERESP, L'Hospitalet de Llobregat, Catalonia, Spain.
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authors.affiliation: National Cancer Institute, NIH, Bethesda, Maryland.
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authors.forename: Vittorio
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authors.affiliation: Hellenic Health Foundation, Athens, Greece. Academy of Athens, Athens, Greece. University of Athens Medical School, Athens, Greece.
authors.forename: Antonia
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authors.lastname: Trichopoulou
authors.affiliation: 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.
authors.forename: H B As
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.affiliation: Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France. Université Paris Sud, Villejuif, France. Institut Gustave Roussy, Villejuif, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.affiliation: 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.
authors.forename: Elisabete
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authors.lastname: Weiderpass
authors.affiliation: Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Ekström
authors.affiliation: Imperial College London, London, United Kingdom.
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authors.forename: Anne
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authors.affiliation: 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.
authors.forename: María-José
authors.initials: MJ
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authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
authors.forename: Ruth C
authors.initials: RC
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authors.affiliation: National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Allan
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authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Michael
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mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000821:virology*; D016022:Case-Control Studies; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D009959:Oropharyngeal Neoplasms / Q000276:immunology / Q000821:virology*; D030361:Papillomavirus Infections / Q000276:immunology; D012097:Repressor Proteins / Q000276:immunology*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins