TY - JOUR
T1 - The influence of hormonal factors on the risk of developing cervical cancer and pre-cancer
T2 - Results from the EPIC cohort
AU - Roura, Esther
AU - Travier, Noémie
AU - Waterboer, Tim
AU - de Sanjosé, Silvia
AU - Xavier Bosch, F.
AU - Pawlita, Michael
AU - Pala, Valeria
AU - Weiderpass, Elisabete
AU - Margall, Núria
AU - Dillner, Joakim
AU - Gram, Inger T.
AU - Tjønneland, Anne
AU - Munk, Christian
AU - Palli, Domenico
AU - Khaw, Kay Tee
AU - Overvad, Kim
AU - Clavel-Chapelon, Françoise
AU - Mesrine, Sylvie
AU - Fournier, Agnès
AU - Fortner, Renée T.
AU - Ose, Jennifer
AU - Steffen, Annika
AU - Trichopoulou, Antonia
AU - Lagiou, Pagona
AU - Orfanos, Philippos
AU - Masala, Giovanna
AU - Tumino, Rosario
AU - Sacerdote, Carlotta
AU - Polidoro, Silvia
AU - Mattiello, Amalia
AU - Lund, Eiliv
AU - Peeters, Petra H.
AU - Bueno-De-Mesquita, H. B.
AU - Ramón Quirós, J.
AU - Sánchez, María José
AU - Navarro, Carmen
AU - Barricarte, Aurelio
AU - Larrañaga, Nerea
AU - Ekström, Johanna
AU - Lindquist, David
AU - Idahl, Annika
AU - Travis, Ruth C.
AU - Merritt, Melissa A.
AU - Gunter, Marc J.
AU - Rinaldi, Sabina
AU - Tommasino, Massimo
AU - Franceschi, Silvia
AU - Riboli, Elio
AU - Castellsagué, Xavier
N1 - Publisher Copyright:
Copyright: © 2016 Roura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/1
Y1 - 2016/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85016121604
U2 - 10.1371/journal.pone.0147029
DO - 10.1371/journal.pone.0147029
M3 - Article
SN - 1932-6203
VL - 11
JO - PLoS ONE
JF - PLoS ONE
IS - 1
M1 - e0147029
ER -
SDG 3 Salute e benessere