No causal association identified for human papillomavirus infections in lung cancer.
Human papillomavirus (HPV) infections have been implicated in lung carcinogenesis, but causal associations remain uncertain. We evaluated a potential causal role for HPV infections in lung cancer through an analysis involving serology, tumor DNA, RNA, and p16 protein expression. Association between type-specific HPV antibodies and risk of lung cancer was examined among 3,083 cases and 4,328 controls in two case-control studies (retrospective) and one nested case-control study (prospective design). Three hundred and thirty-four available tumors were subjected to pathologic evaluation and subsequent HPV genotyping following stringent conditions to detect all high-risk and two low-risk HPV types. All HPV DNA-positive tumors were further tested for the expression of p16 protein and type-specific HPV mRNA. On the basis of the consistency of the results, although HPV11 and HPV31 E6 antibodies were associated with lung cancer risk in the retrospective study, no association was observed in the prospective design. Presence of type-specific antibodies correlated poorly with the presence of the corresponding HPV DNA in the tumor. Although nearly 10% of the lung tumors were positive for any HPV DNA (7% for HPV16 DNA), none expressed the viral oncogenes. No association was observed between HPV antibodies or DNA and lung cancer survival. In conclusion, we found no supportive evidence for the hypothesized causal association between HPV infections and lung cancer.
Authors' Affiliations: Genetic Epidemiology Group;
Devasena
D
Anantharaman
Infections and Cancer Biology Group;
Tarik
T
Gheit
Infection and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg;
Tim
T
Waterboer
Infection and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg;
Gordana
G
Halec
Molecular Pathology Group, International Agency for Research on Cancer, Lyon;
Christine
C
Carreira
Authors' Affiliations: Genetic Epidemiology Group; Digestive Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran;
Behnoush
B
Abedi-Ardekani
Infections and Cancer Biology Group;
Sandrine
S
McKay-Chopin
Department of Epidemiology and Prevention, Russian Cancer Research Center, Moscow, Russia;
David
D
Zaridze
Department of Epidemiology and Prevention, Russian Cancer Research Center, Moscow, Russia;
Anush
A
Mukeria
Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Lodz;
Neonila
N
Szeszenia-Dabrowska
M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland;
Jolanta
J
Lissowska
Institute of Public Health, Bucharest, Romania;
Dana
D
Mates
Department of Preventive Medicine, Palacky University, Olomouc;
Vladimir
V
Janout
Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno;
Lenka
L
Foretova
Institute of Hygiene and Epidemiology, 1 Faculty of Medicine, Charles University in Prague, Prague, Czech Republic;
Vladimir
V
Bencko
National Institute of Environmental Health, Budapest, Hungary;
Peter
P
Rudnai
Regional Authority of Public Health, Banská Bystrica, Slovakia;
Eleonora
E
Fabianova
Danish Cancer Society Research Center, Copenhagen, Denmark;
Anne
A
Tjønneland
Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford;
Ruth C
RC
Travis
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany;
Heiner
H
Boeing
Public Health Directorate, Asturias, Spain;
J Ramón
JR
Quirós
Department of Radiation Sciences, Oncology, Umeå University, Umeå;
Mikael
M
Johansson
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy;
Vittorio
V
Krogh
The School of Public health, Imperial College London, London, United Kingdom; National Institute for Public Health and the Environment (RIVM), Bilthoven; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands;
H Bas
HB
Bueno-de-Mesquita
First Department of Critical Care Medicine & Pulmonary Services, University of Athens Medical School, Evangelismos Hospital; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece;
Anastasia
A
Kotanidou
INSERM, Centre for research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team; University Paris Sud; IGR, Villejuif, France;
Françoise
F
Clavel-Chapelon
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Community Medicine, Faculty of Health Sciences, The Artic University of Norway, Tromsø; Department of Research, Cancer Registry of Norway, Oslo, Norway; and Samfundet Folkhälsan, Helsinki, Finland.
Elisabete
E
Weiderpass
Authors' Affiliations: Genetic Epidemiology Group;
Mattias
M
Johansson
Infection and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg;
Michael
M
Pawlita
Authors' Affiliations: Genetic Epidemiology Group;
Ghislaine
G
Scelo
Infections and Cancer Biology Group;
Massimo
M
Tommasino
Authors' Affiliations: Genetic Epidemiology Group; gep@iarc.fr.
Paul
P
Brennan
D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000276:immunology; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D052140:Human papillomavirus 11 / Q000276:immunology; D052162:Human papillomavirus 16 / Q000276:immunology; D052161:Human papillomavirus 18 / Q000276:immunology; D052163:Human papillomavirus 6 / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications* / Q000401:mortality / Q000821:virology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000276:immunology; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000209:etiology* / Q000235:genetics / Q000821:virology; D011446:Prospective Studies; D012367:RNA, Viral / Q000096:biosynthesis; D012189:Retrospective Studies
D000914:Antibodies, Viral; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; C469553:E6 protein, Human papillomavirus type 11; C572886:E6 protein, Human papillomavirus type 31; D009363:Neoplasm Proteins; D009856:Oncogene Proteins, Viral; D012367:RNA, Viral