The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort.

<h4>Background</h4>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 fac...

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Main Authors: Esther Roura, Noémie Travier, Tim Waterboer, Silvia de Sanjosé, F Xavier Bosch, Michael Pawlita, Valeria Pala, Elisabete Weiderpass, Núria Margall, Joakim Dillner, Inger T Gram, Anne Tjønneland, Christian Munk, Domenico Palli, Kay-Tee Khaw, Kim Overvad, Françoise Clavel-Chapelon, Sylvie Mesrine, Agnès Fournier, Renée T Fortner, Jennifer Ose, Annika Steffen, Antonia Trichopoulou, Pagona Lagiou, Philippos Orfanos, Giovanna Masala, Rosario Tumino, Carlotta Sacerdote, Silvia Polidoro, Amalia Mattiello, Eiliv Lund, Petra H Peeters, H B as Bueno-de-Mesquita, J Ramón Quirós, María-José Sánchez, Carmen Navarro, Aurelio Barricarte, Nerea Larrañaga, Johanna Ekström, David Lindquist, Annika Idahl, Ruth C Travis, Melissa A Merritt, Marc J Gunter, Sabina Rinaldi, Massimo Tommasino, Silvia Franceschi, Elio Riboli, Xavier Castellsagué
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0147029
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author Esther Roura
Noémie Travier
Tim Waterboer
Silvia de Sanjosé
F Xavier Bosch
Michael Pawlita
Valeria Pala
Elisabete Weiderpass
Núria Margall
Joakim Dillner
Inger T Gram
Anne Tjønneland
Christian Munk
Domenico Palli
Kay-Tee Khaw
Kim Overvad
Françoise Clavel-Chapelon
Sylvie Mesrine
Agnès Fournier
Renée T Fortner
Jennifer Ose
Annika Steffen
Antonia Trichopoulou
Pagona Lagiou
Philippos Orfanos
Giovanna Masala
Rosario Tumino
Carlotta Sacerdote
Silvia Polidoro
Amalia Mattiello
Eiliv Lund
Petra H Peeters
H B as Bueno-de-Mesquita
J Ramón Quirós
María-José Sánchez
Carmen Navarro
Aurelio Barricarte
Nerea Larrañaga
Johanna Ekström
David Lindquist
Annika Idahl
Ruth C Travis
Melissa A Merritt
Marc J Gunter
Sabina Rinaldi
Massimo Tommasino
Silvia Franceschi
Elio Riboli
Xavier Castellsagué
author_facet Esther Roura
Noémie Travier
Tim Waterboer
Silvia de Sanjosé
F Xavier Bosch
Michael Pawlita
Valeria Pala
Elisabete Weiderpass
Núria Margall
Joakim Dillner
Inger T Gram
Anne Tjønneland
Christian Munk
Domenico Palli
Kay-Tee Khaw
Kim Overvad
Françoise Clavel-Chapelon
Sylvie Mesrine
Agnès Fournier
Renée T Fortner
Jennifer Ose
Annika Steffen
Antonia Trichopoulou
Pagona Lagiou
Philippos Orfanos
Giovanna Masala
Rosario Tumino
Carlotta Sacerdote
Silvia Polidoro
Amalia Mattiello
Eiliv Lund
Petra H Peeters
H B as Bueno-de-Mesquita
J Ramón Quirós
María-José Sánchez
Carmen Navarro
Aurelio Barricarte
Nerea Larrañaga
Johanna Ekström
David Lindquist
Annika Idahl
Ruth C Travis
Melissa A Merritt
Marc J Gunter
Sabina Rinaldi
Massimo Tommasino
Silvia Franceschi
Elio Riboli
Xavier Castellsagué
author_sort Esther Roura
collection DOAJ
description <h4>Background</h4>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).<h4>Methods and findings</h4>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).<h4>Conclusions</h4>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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spelling doaj-art-10061e76bbed42be9cfcaf1fd60f8c2b2025-08-20T03:10:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01111e014702910.1371/journal.pone.0147029The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort.Esther RouraNoémie TravierTim WaterboerSilvia de SanjoséF Xavier BoschMichael PawlitaValeria PalaElisabete WeiderpassNúria MargallJoakim DillnerInger T GramAnne TjønnelandChristian MunkDomenico PalliKay-Tee KhawKim OvervadFrançoise Clavel-ChapelonSylvie MesrineAgnès FournierRenée T FortnerJennifer OseAnnika SteffenAntonia TrichopoulouPagona LagiouPhilippos OrfanosGiovanna MasalaRosario TuminoCarlotta SacerdoteSilvia PolidoroAmalia MattielloEiliv LundPetra H PeetersH B as Bueno-de-MesquitaJ Ramón QuirósMaría-José SánchezCarmen NavarroAurelio BarricarteNerea LarrañagaJohanna EkströmDavid LindquistAnnika IdahlRuth C TravisMelissa A MerrittMarc J GunterSabina RinaldiMassimo TommasinoSilvia FranceschiElio RiboliXavier Castellsagué<h4>Background</h4>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).<h4>Methods and findings</h4>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).<h4>Conclusions</h4>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.https://doi.org/10.1371/journal.pone.0147029
spellingShingle Esther Roura
Noémie Travier
Tim Waterboer
Silvia de Sanjosé
F Xavier Bosch
Michael Pawlita
Valeria Pala
Elisabete Weiderpass
Núria Margall
Joakim Dillner
Inger T Gram
Anne Tjønneland
Christian Munk
Domenico Palli
Kay-Tee Khaw
Kim Overvad
Françoise Clavel-Chapelon
Sylvie Mesrine
Agnès Fournier
Renée T Fortner
Jennifer Ose
Annika Steffen
Antonia Trichopoulou
Pagona Lagiou
Philippos Orfanos
Giovanna Masala
Rosario Tumino
Carlotta Sacerdote
Silvia Polidoro
Amalia Mattiello
Eiliv Lund
Petra H Peeters
H B as Bueno-de-Mesquita
J Ramón Quirós
María-José Sánchez
Carmen Navarro
Aurelio Barricarte
Nerea Larrañaga
Johanna Ekström
David Lindquist
Annika Idahl
Ruth C Travis
Melissa A Merritt
Marc J Gunter
Sabina Rinaldi
Massimo Tommasino
Silvia Franceschi
Elio Riboli
Xavier Castellsagué
The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort.
PLoS ONE
title The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort.
title_full The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort.
title_fullStr The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort.
title_full_unstemmed The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort.
title_short The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort.
title_sort influence of hormonal factors on the risk of developing cervical cancer and pre cancer results from the epic cohort
url https://doi.org/10.1371/journal.pone.0147029
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