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 As
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
N1 - This work was supported by the Intramural Research Program of the National
Cancer Institute (to A.R. Kreimer).
The EPIC study has been supported by the Europe Against Cancer Program of
the European Commission (SANCO); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum,
German Federal Ministry of Education and Research;
Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of
Health, Spanish Regional Governments of Andalucia, Asturias, Basque Country,
Murcia, and Navarra; Catalan Institute of Oncology, Spain; the ISCIII of the
Spanish Ministry of Health (RETICC DR06/0020); Cancer Research UK; Medical
Research Council, United Kingdom; Greek Ministry of Health; Stavros Niarchos
Foundation; Hellenic Health Foundation; Italian Association for Research on
Cancer (AIRC); Italian National Research Council, Fondazione-Istituto Banco
Napoli, Italy; Associazione Italiana per la Ricerca sul Cancro-AIRC-Milan;
Compagnia di San Paolo; Dutch Ministry of Public Health, Welfare, and Sports;
World Cancer Research Fund; Swedish Cancer Society; Swedish Scientific
Council; Regional Government of V€asterbotten, Sweden; NordForsk (Centre
of excellence programme HELGA), Norway; French League against Cancer
(LNCC), France; National Institute for Health and Medical Research (INSERM),
France; Mutuelle Generale de l'Education Nationale (MGEN), France; 3M Co,
France; Gustave Roussy Institute (IGR), France; and General Councils of France
(to P. Brennan).
The ARCAGE study was supported by the grant from European Commission's
5th Framework Program (contract QLK1-2001-00182). This project was
partly funded by the Health General Directorate of the French Social Affairs and
Health Ministry. The serology testing was supported in part by a grant from the
European Commission's 7th Framework Program (contract FP7-HEALTH-
2011–282562; to P. Brennan).
PLCO was supported by the Intramural Research Program of the Division of
Cancer Epidemiology and Genetics and by contracts from the Division of
Cancer Prevention, National Cancer Institute, NIH, DHHS.
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: 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.
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 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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Antibodies, Viral
KW - Carcinoma, Squamous Cell
KW - Case-Control Studies
KW - Cohort Studies
KW - Enzyme-Linked Immunosorbent Assay
KW - Female
KW - Human papillomavirus 16
KW - Humans
KW - Male
KW - Middle Aged
KW - Oncogene Proteins, Viral
KW - Oropharyngeal Neoplasms
KW - Papillomavirus Infections
KW - Repressor Proteins
KW - Risk Factors
KW - Young Adult
KW - Journal Article
KW - Research Support, N.I.H., Intramural
KW - Research Support, Non-U.S. Gov't
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 -
