Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 135, Issue 2, Pages 453-466Publisher
WILEY
DOI: 10.1002/ijc.28666
Keywords
cohort study; cervical cancer; smoking; Human Papillomavirus serology; EPIC
Categories
Funding
- Merck/SPMSD
- MSD/Merck
- Merck Co., Inc
- SPMSD
- Instituto de Salud Carlos III (Spanish Government) [FIS PI08/1308, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095, RD12/0036/0056, RD12/0036/0018, CIBERESP]
- Agencia de Gestio d'Ajuts Universitaris i de Recerca-Generalitat de Catalunya (Catalonian Government) [AGAUR 2005SGR00695, 2009SGR939, 2009SGR126]
- European Commission (DG-SANCO)
- International Agency for Research on Cancer
- Health Research Fund (FIS) of the Spanish Ministry of Health [Exp P10710130]
- Regional Government of Andalucia
- Regional Government of Asturias
- Regional Government of Basque Country
- Regional Government of Murcia
- Regional Governments of Navarra
- Catalan Institute of Oncology [6236]
- La Caixa (Spain) [BM 06-130, RTICC-RD06/10091]
- Danish Cancer Society (Denmark)
- Ligue contre le Cancer
- Mutuelle Generale de l'Education Nationale
- Institut National de la Sante et de la Recherche Medicale (INSERM) (France)
- Deutsche Krebshilfe
- Deutsches Krebsforschungszentrum
- Hellenic Health Foundation (Greece)
- Italian Association for Research on Cancer (AIRC)
- National Research Council (Italy)
- Dutch Ministry of Public Health
- Welfare and Sports
- Netherlands Cancer Registry (NKR)
- LK Research Funds
- Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland)
- World Cancer Research Fund (WCRF)
- Regional Government of Skane and Vasterbotten (Sweden)
- Cancer Research UK, Medical Research Council (United Kingdom)
- Norwegian Research Council, Norwegian Cancer Society, University of Tromso (Norway)
- Institut Gustave Roussy
- Federal Ministry of Education and Research (Germany)
- Statistics Netherlands (The Netherlands)
- Swedish Cancer Society
- Swedish Scientific Council
- Cancer Research UK [16491, 14136] Funding Source: researchfish
- Medical Research Council [G1000143, G0401527] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10114] Funding Source: researchfish
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A total of 308,036 women were selected from the European Prospective Investigation into Cancer and Nutrition (EPIC) study to evaluate the association between tobacco smoking and the risk of cervical intraepithelial neoplasia of grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). At baseline, participants completed a questionnaire and provided blood samples. During a mean follow-up time of 9 years, 261 ICC cases and 804 CIN3/CIS cases were reported. In a nested case-control study, the baseline sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11, 16, 18, 31, 33, 35, 45, 52, 58, and antibodies against Chlamydia trachomatis (CT), and Human Herpes Virus 2 (HHV-2). Cervical samples were not available for HPV-DNA analysis in this study. Multivariate analyses were used to estimate associations between smoking and risk of CIN3/CIS and ICC in the cohort and the case-control studies. In the cohort analyses smoking status, duration and intensity showed a two-fold increased risk of CIN3/CIS and ICC, while time since quitting was associated with a two-fold reduced risk. In the nested case-control study, consistent associations were observed after adjustment for HPV, CT and HHV-2 serostatus, in both HPV seronegative and seropositive women. Results from this large prospective study confirm the role of tobacco smoking as an important risk factor for both CIN3/CIS and ICC, even after taking into account HPV exposure as determined by HPV serology. The strong beneficial effect of quitting smoking is an important finding that will further support public health policies for smoking cessation. What's new? Tobacco smoking is a cited cause of cervical cancer, but whether it causes cervical malignancy independent of human papillomavirus (HPV) infection is unclear. Here, strong associations were found between most measures of tobacco smoking and the risk of cervical intraepithelial neoplasia of grade 3/carcinoma in situ and invasive cervical cancer, after taking into account past exposure to HPV infection. Quitting smoking was associated with a 2-fold risk reduction. The findings confirm the role of tobacco smoking in cervical carcinogenesis and show that quitting the habit has important benefits for cancer protection.
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