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

Krystle A Lang Kuhs, Devasena Anantharaman, Tim Waterboer, Mattias Johansson, Paul Brennan, Angelika Michel, Martina Willhauck-Fleckenstein, Mark P Purdue, Ivana Holcatova, Wolfgang Ahrens, Pagona Lagiou, Jerry Polesel, Lorenzo Simonato, Franco Merletti, Claire M Healy, Kristina Kjaerheim, David I Conway, Tatiana MacFarlane, Peter Thomson, Xavier CastellsagueAriana Znaor, Amanda Black, Wen-Yi Huang, Vittorio Krogh, Antonia Trichopoulou, H Bas Bueno-de-Mesquita, Francoise Clavel-Chapelon, Elisabete Weiderpass, Johanna Ekström, Elio Riboli, Anne Tjonneland, Maria-Jose Sanchez, Ruth C Travis, Allan Hildesheim, Michael Pawlita, Aimee R Kreimer

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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: 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 & <1000) or ii) high seroreactivity (MFI≥1000). 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 3 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.

Original languageEnglish
Pages (from-to)683-689
Number of pages7
JournalCancer Epidemiology, Biomarkers and Prevention
Issue number4
Early online date26 Jan 2015
Publication statusPublished - Apr 2015

Bibliographical note

Date of Acceptance: 15/01/2015

Copyright © 2015, American Association for Cancer Research.

We would like to thank the following people for their contributions to the manuscript: David Castenson (Information Management Services, Calverton MD, USA); Dana Mates (Institute of Public Health, Bucharest, Romania); Vladimir Bencko (Charles University in Prague, Czech Republic); Victor Wünsch-Filho (School of Public Health, University of Sao Paulo, Sao Paulo, Brazil); Elena Matos(Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina); and Jose Eluf-Neto (Universidade de São Paulo, Sao Paulo, Brazil). We acknowledge contribution of Professor Gary J Macfarlane, Dr Ann-Marie Biggs, Professor Martin Tickle, Professor Phil Sloan and Professor Nalin Thakker with study conduct in UK centers.


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