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Cancer Res. 2014 Jul 1;74(13):3525-34. doi: 10.1158/0008-5472.CAN-13-3548. Epub 2014 Apr 23.

No causal association identified for human papillomavirus infections in lung cancer.

Author information

1
Authors' Affiliations: Genetic Epidemiology Group;
2
Infections and Cancer Biology Group;
3
Infection and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg;
4
Molecular Pathology Group, International Agency for Research on Cancer, Lyon;
5
Authors' Affiliations: Genetic Epidemiology Group; Digestive Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran;
6
Department of Epidemiology and Prevention, Russian Cancer Research Center, Moscow, Russia;
7
Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Lodz;
8
M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland;
9
Institute of Public Health, Bucharest, Romania;
10
Department of Preventive Medicine, Palacky University, Olomouc;
11
Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno;
12
Institute of Hygiene and Epidemiology, 1 Faculty of Medicine, Charles University in Prague, Prague, Czech Republic;
13
National Institute of Environmental Health, Budapest, Hungary;
14
Regional Authority of Public Health, Banská Bystrica, Slovakia;
15
Danish Cancer Society Research Center, Copenhagen, Denmark;
16
Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford;
17
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany;
18
Public Health Directorate, Asturias, Spain;
19
Department of Radiation Sciences, Oncology, Umeå University, Umeå;
20
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy;
21
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;
22
First Department of Critical Care Medicine & Pulmonary Services, University of Athens Medical School, Evangelismos Hospital; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece;
23
INSERM, Centre for research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team; University Paris Sud; IGR, Villejuif, France;
24
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.
25
Authors' Affiliations: Genetic Epidemiology Group; gep@iarc.fr.

Abstract

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.

PMID:
24760422
DOI:
10.1158/0008-5472.CAN-13-3548
[Indexed for MEDLINE]
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