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 Castellsague; Ariana 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

doi:10.1158/1055-9965.EPI-14-1217

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 Castellsague

Ariana 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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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: 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 language	English
Pages (from-to)	683-689
Number of pages	7
Journal	Cancer Epidemiology, Biomarkers and Prevention
Volume	24
Issue number	4
Early online date	26 Jan 2015
DOIs	https://doi.org/10.1158/1055-9965.EPI-14-1217
Publication status	Published - Apr 2015

Bibliographical note

Date of Acceptance: 15/01/2015

Copyright © 2015, American Association for Cancer Research.

Acknowledgements
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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Submitted_HPV16 E6 Epidemiology
This is the author's final draft of an article published in Cancer Epidemiology, Biomarkers & Prevention. The final published version is available online at http://cebp.aacrjournals.org/content/24/4/683
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Lang Kuhs, K. A., Anantharaman, D., Waterboer, T., Johansson, M., Brennan, P., Michel, A., Willhauck-Fleckenstein, M., Purdue, M. P., Holcatova, I., Ahrens, W., Lagiou, P., Polesel, J., Simonato, L., Merletti, F., Healy, C. M., Kjaerheim, K., Conway, D. I., MacFarlane, T., Thomson, P., ... Kreimer, A. R. (2015). Human Papillomavirus 16 E6 Antibodies in Individuals Without Diagnosed Cancer: A Pooled Analysis. Cancer Epidemiology, Biomarkers and Prevention, 24(4), 683-689. https://doi.org/10.1158/1055-9965.EPI-14-1217

Lang Kuhs, KA, Anantharaman, D, Waterboer, T, Johansson, M, Brennan, P, Michel, A, Willhauck-Fleckenstein, M, Purdue, MP, Holcatova, I, Ahrens, W, Lagiou, P, Polesel, J, Simonato, L, Merletti, F, Healy, CM, Kjaerheim, K, Conway, DI, MacFarlane, T, Thomson, P, Castellsague, X, Znaor, A, Black, A, Huang, W-Y, Krogh, V, Trichopoulou, A, Bueno-de-Mesquita, HB, Clavel-Chapelon, F, Weiderpass, E, Ekström, J, Riboli, E, Tjonneland, A, Sanchez, M-J, Travis, RC, Hildesheim, A, Pawlita, M & Kreimer, AR 2015, 'Human Papillomavirus 16 E6 Antibodies in Individuals Without Diagnosed Cancer: A Pooled Analysis', Cancer Epidemiology, Biomarkers and Prevention, vol. 24, no. 4, pp. 683-689. https://doi.org/10.1158/1055-9965.EPI-14-1217

@article{80227d567b84417ea20856d50f8e0b84,

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: 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.",

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

note = "Date of Acceptance: 15/01/2015 Copyright {\textcopyright} 2015, American Association for Cancer Research. Acknowledgements 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 W{\"u}nsch-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 S{\~a}o 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. ",

year = "2015",

month = apr,

doi = "10.1158/1055-9965.EPI-14-1217",

language = "English",

volume = "24",

pages = "683--689",

journal = "Cancer Epidemiology, Biomarkers and Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research Inc.",

number = "4",

}

TY - JOUR

T1 - Human Papillomavirus 16 E6 Antibodies in Individuals Without Diagnosed Cancer

T2 - A Pooled Analysis

AU - Lang Kuhs, Krystle A

AU - Anantharaman, Devasena

AU - Waterboer, Tim

AU - Johansson, Mattias

AU - Brennan, Paul

AU - Michel, Angelika

AU - Willhauck-Fleckenstein, Martina

AU - Purdue, Mark P

AU - Holcatova, Ivana

AU - Ahrens, Wolfgang

AU - Lagiou, Pagona

AU - Polesel, Jerry

AU - Simonato, Lorenzo

AU - Merletti, Franco

AU - Healy, Claire M

AU - Kjaerheim, Kristina

AU - Conway, David I

AU - MacFarlane, Tatiana

AU - Thomson, Peter

AU - Castellsague, Xavier

AU - Znaor, Ariana

AU - Black, Amanda

AU - Huang, Wen-Yi

AU - Krogh, Vittorio

AU - Trichopoulou, Antonia

AU - Bueno-de-Mesquita, H Bas

AU - Clavel-Chapelon, Francoise

AU - Weiderpass, Elisabete

AU - Ekström, Johanna

AU - Riboli, Elio

AU - Tjonneland, Anne

AU - Sanchez, Maria-Jose

AU - Travis, Ruth C

AU - Hildesheim, Allan

AU - Pawlita, Michael

AU - Kreimer, Aimee R

N1 - Date of Acceptance: 15/01/2015 Copyright © 2015, American Association for Cancer Research. Acknowledgements 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.

PY - 2015/4

Y1 - 2015/4

N2 - 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.

AB - 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.

U2 - 10.1158/1055-9965.EPI-14-1217

DO - 10.1158/1055-9965.EPI-14-1217

M3 - Article

C2 - 25623733

SN - 1055-9965

VL - 24

SP - 683

EP - 689

JO - Cancer Epidemiology, Biomarkers and Prevention

JF - Cancer Epidemiology, Biomarkers and Prevention

IS - 4

ER -

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

Abstract

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