期刊
PLOS ONE
卷 11, 期 1, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0147029
关键词
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资金
- Instituto de Salud Carlos III (Spanish Government) [FIS PI08/1308, PI13/00053, 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, 2014SGR1077, 2014SGR2016]
- European Commission (DG-SANCO)
- International Agency for Research on Cancer
- Health Research Fund (FIS) of the Spanish Ministry of Health [P10710130]
- Regional Governments of Andalucia, Asturias, Basque Country, Murcia [6236]
- Navarra and the Catalan Institute of Oncology, La Caixa (Spain) [BM 06-130, RTICC-RD06/10091]
- Danish Cancer Society (Denmark)
- Ligue contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France)
- Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany)
- Hellenic Health Foundation (Greece)
- Italian Association for Research on Cancer (AIRC) and National Research Council (Italy)
- Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR)
- LK Research Funds
- Dutch Prevention Funds
- Dutch ZON (Zorg Onderzoek Nederland)
- World Cancer Research Fund (WCRF)
- Statistics Netherlands (The Netherlands)
- Swedish Cancer Society, Swedish Scientific Council and 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)
- 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
Background In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). Methods and Findings We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the 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 and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of fullterm pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for >= 15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95% CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7). Conclusions Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.
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