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 Holcátová; Wolfgang Ahrens; Pagona Lagiou; Jerry Polesel; Lorenzo Simonato; Franco Merletti; Claire M. Healy; Kristina Kjaerheim; David I. Conway; Tatiana V. Macfarlane; Peter Thomson; Xavier Castellsagué; Ariana Znaor; Amanda Black; Wen Yi Huang; Vittorio Krogh; Antonia Trichopoulou; H. B.A.S. Bueno-De-Mesquita; Françoise Clavel-Chapelon; Elisabete Weiderpass; Johanna Ekström; Elio Riboli; Anne Tjønneland; María José Sánchez; Ruth C. Travis; Allan Hildesheim; Michael Pawlita; Aimée 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 Holcátová, Wolfgang Ahrens, Pagona Lagiou, Jerry Polesel, Lorenzo Simonato, Franco Merletti, Claire M. Healy, Kristina Kjaerheim, David I. Conway, Tatiana V. Macfarlane, Peter Thomson, Xavier CastellsaguéAriana Znaor, Amanda Black, Wen Yi Huang, Vittorio Krogh, Antonia Trichopoulou, H. B.A.S. Bueno-De-Mesquita, Françoise Clavel-Chapelon, Elisabete Weiderpass, Johanna Ekström, Elio Riboli, Anne Tjønneland, María José Sánchez, Ruth C. Travis, Allan Hildesheim, Michael Pawlita, Aimée R. Kreimer

Research output: Contribution to journal › Article › peer-review

54 Scopus citations

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 againstHPV16 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 observedwithmoderateHPV16 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 diagnosedHPV-drivencancer,especiallythosewithseropositivityagainst other HPV16 proteins, may harbor a biologically relevant HPV16 infection. Cancer Epidemiol Biomarkers Prev; 24(4); 683-9.

Original language	English
Pages (from-to)	683-689
Number of pages	7
Journal	Cancer Epidemiology Biomarkers and Prevention
Volume	24
Issue number	4
DOIs	https://doi.org/10.1158/1055-9965.EPI-14-1217
State	Published - Apr 1 2015

Bibliographical note

Publisher Copyright:
© 2015 AACR.

Funding

Funders	Funder number
Cancerfonden
National Childhood Cancer Registry – National Cancer Institute
World Cancer Research Fund International
National Childhood Cancer Registry – National Cancer Institute	ZIACP010209
Seventh Framework Programme	282562

ASJC Scopus subject areas

Epidemiology
Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1158/1055-9965.EPI-14-1217

Cite this

Lang Kuhs, K. A., Anantharaman, D., Waterboer, T., Johansson, M., Brennan, P., Michel, A., Willhauck-Fleckenstein, M., Purdue, M. P., Holcátová, I., Ahrens, W., Lagiou, P., Polesel, J., Simonato, L., Merletti, F., Healy, C. M., Kjaerheim, K., Conway, D. I., Macfarlane, T. V., 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

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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 againstHPV16 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 observedwithmoderateHPV16 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 diagnosedHPV-drivencancer,especiallythosewithseropositivityagainst other HPV16 proteins, may harbor a biologically relevant HPV16 infection. Cancer Epidemiol Biomarkers Prev; 24(4); 683-9.",

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 Holc{\'a}tov{\'a} 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 Macfarlane, {Tatiana V.} and Peter Thomson and Xavier Castellsagu{\'e} and Ariana Znaor and Amanda Black and Huang, {Wen Yi} and Vittorio Krogh and Antonia Trichopoulou and Bueno-De-Mesquita, {H. B.A.S.} and Fran{\c c}oise Clavel-Chapelon and Elisabete Weiderpass and Johanna Ekstr{\"o}m and Elio Riboli and Anne Tj{\o}nneland and S{\'a}nchez, {Mar{\'i}a Jos{\'e}} and Travis, {Ruth C.} and Allan Hildesheim and Michael Pawlita and Kreimer, {Aim{\'e}e R.}",

note = "Publisher Copyright: {\textcopyright} 2015 AACR.",

year = "2015",

month = apr,

day = "1",

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

language = "English",

volume = "24",

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Lang Kuhs, KA, Anantharaman, D, Waterboer, T, Johansson, M, Brennan, P, Michel, A, Willhauck-Fleckenstein, M, Purdue, MP, Holcátová, I, Ahrens, W, Lagiou, P, Polesel, J, Simonato, L, Merletti, F, Healy, CM, Kjaerheim, K, Conway, DI, Macfarlane, TV, Thomson, P, Castellsagué, X, Znaor, A, Black, A, Huang, WY, Krogh, V, Trichopoulou, A, Bueno-De-Mesquita, HBAS, Clavel-Chapelon, F, Weiderpass, E, Ekström, J, Riboli, E, Tjønneland, A, Sánchez, MJ, 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

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 - Holcátová, 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 V.

AU - Thomson, Peter

AU - Castellsagué, Xavier

AU - Znaor, Ariana

AU - Black, Amanda

AU - Huang, Wen Yi

AU - Krogh, Vittorio

AU - Trichopoulou, Antonia

AU - Bueno-De-Mesquita, H. B.A.S.

AU - Clavel-Chapelon, Françoise

AU - Weiderpass, Elisabete

AU - Ekström, Johanna

AU - Riboli, Elio

AU - Tjønneland, Anne

AU - Sánchez, María José

AU - Travis, Ruth C.

AU - Hildesheim, Allan

AU - Pawlita, Michael

AU - Kreimer, Aimée R.

PY - 2015/4/1

Y1 - 2015/4/1

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: 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 againstHPV16 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 observedwithmoderateHPV16 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 diagnosedHPV-drivencancer,especiallythosewithseropositivityagainst other HPV16 proteins, may harbor a biologically relevant HPV16 infection. Cancer Epidemiol Biomarkers Prev; 24(4); 683-9.

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: 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 againstHPV16 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 observedwithmoderateHPV16 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 diagnosedHPV-drivencancer,especiallythosewithseropositivityagainst other HPV16 proteins, may harbor a biologically relevant HPV16 infection. Cancer Epidemiol Biomarkers Prev; 24(4); 683-9.

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Human papillomavirus 16 E6 antibodies in individuals without diagnosed cancer: A pooled analysis

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

UN SDGs

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