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

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

doi:10.1371/journal.pone.0147029

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

Roura E, Travier N, Waterboer T, de Sanjosé S, Bosch FX, Pawlita M, Pala V, Weiderpass E, Margall N, Dillner J, Gram IT, Tjønneland A, Munk C, Palli D, Khaw KT, Overvad K, Clavel-Chapelon F, Mesrine S, Fournier A, Fortner RT, Ose J, Steffen A, Trichopoulou A, Lagiou P, Orfanos P, Masala G, Tumino R, Sacerdote C, Polidoro S, Mattiello A, Lund E, Peeters PH, Bueno-de-Mesquita HB, Quirós JR, Sánchez MJ, Navarro C, Barricarte A, Larrañaga N, Ekström J, Lindquist D, Idahl A, Travis RC, Merritt MA, Gunter MJ, Rinaldi S, Tommasino M, Franceschi S, Riboli E, Castellsagué X

Published January 25, 2016 PLoS One, 11(1), e0147029

DOI 10.1371/journal.pone.0147029 PMID 26808155 PMC PMC4726518

Abstract

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 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.

Topics

General Gynecology › Gynecologic Oncology › Cervical Cancer · Contraception › Oral Contraceptives › Cancer Risk

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

E Roura, N Travier, Timothy Waterboer, T Waterboer, S Sanjosé, Mike Pawlita, M Pawlita, V Pala, E Weiderpass, N Margall, J Dillner, I Gram, A Tjønneland, C Munk, D Palli, K Khaw, K Overvad, F Clavel-Chapelon, S Mesrine, A Fournier, R Fortner, Jen Ose, Jenny Ose, J Ose, A Steffen, A Trichopoulou, P Lagiou, P Orfanos, G Masala, R Tumino, C Sacerdote, S Polidoro, A Mattiello, E Lund, P Peeters, M Sánchez, C Navarro, A Barricarte, N Larrañaga, J Ekström, Dave Lindquist, D Lindquist, A Idahl, R Travis, M Merritt, M Gunter, S Rinaldi, M Tommasino, S Franceschi, E Riboli, X Castellsagué

PMID 26808155 26808155 DOI 10.1371/journal.pone.0147029 10.1371/journal.pone.0147029 Roura et al. 2016, Roura 2016

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

Abstract

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