Roura, EstherTravier, NoémieWaterboer, Timde Sanjosé, SilviaBosch, F XavierPawlita, MichaelPala, ValeriaWeiderpass, ElisabeteMargall, NúriaDillner, JoakimGram, Inger TTjønneland, AnneMunk, ChristianPalli, DomenicoKhaw, Kay-TeeOvervad, KimClavel-Chapelon, FrançoiseMesrine, SylvieFournier, AgnèsFortner, Renée TOse, JenniferSteffen, AnnikaTrichopoulou, AntoniaLagiou, PagonaOrfanos, PhilipposMasala, GiovannaTumino, RosarioSacerdote, CarlottaPolidoro, SilviaMattiello, AmaliaLund, EilivPeeters, Petra HBueno-de-Mesquita, H B AsQuirós, J RamónSanchez-Perez, Maria-JoseNavarro, CarmenBarricarte, AurelioLarrañaga, NereaEkström, JohannaLindquist, DavidIdahl, AnnikaTravis, Ruth CMerritt, Melissa AGunter, Marc JRinaldi, SabinaTommasino, MassimoFranceschi, SilviaRiboli, ElioCastellsagué, Xavier2016-06-232016-06-232016-01-25Roura E, Travier N, Waterboer T, de Sanjosé S, Bosch FX, Pawlita M, et al. The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort. PLoS ONE 2016; 11(1):e0147029http://hdl.handle.net/10668/2223Journal Article;Corrección en: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0151427BACKGROUND 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 full-term 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.enEstudios de Casos y ControlesNeoplasia Intraepitelial CervicalAnticonceptivosFemeninoHumanosPapillomaviridaeParidadEmbarazoEstudios retrospectivosNeoplasias del cuello uterinoMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control StudiesMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma in Situ::Cervical Intraepithelial NeoplasiaMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Reproductive Control Agents::Contraceptive AgentsMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Organisms::Viruses::DNA Viruses::PapillomaviridaeMedical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::ParityMedical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::PregnancyMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective StudiesMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Female::Uterine Neoplasms::Uterine Cervical Neoplasmsresearch article26808155open access10.1371/journal.pone.01470291932-6203PMC4726518