Advanced

Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: Evidence from the EPIC cohort

Castellsague, Xavier; Pawlita, Michael; Roura, Esther; Margall, Nuria; Waterboer, Tim; Xavier Bosch, F.; de Sanjose, Silvia; Alberto Gonzalez, Carlos; Dillner, Joakim and Gram, Inger T., et al. (2014) In International Journal of Cancer 135(2). p.440-452
Abstract
To evaluate prospectively the association between serological markers of selected infections, including HPV, and risk of developing cervical cancer (CC) and precancer, we performed a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study that included 184 cases of invasive CC (ICC), 425 cases of cervical intraepithelial neoplasia (CIN) grade 3 or carcinoma in situ (CIS), and 1,218 matched control women. At enrollment participants completed lifestyle questionnaires and provided sera. Subjects were followed-up for a median of 9 years. Immunoassays were used to detect serum antibodies to Human Herpes Virus 2 (HHV-2), Chlamydia trachomatis (CT), Chlamydia pneumoniae, L1 proteins of... (More)
To evaluate prospectively the association between serological markers of selected infections, including HPV, and risk of developing cervical cancer (CC) and precancer, we performed a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study that included 184 cases of invasive CC (ICC), 425 cases of cervical intraepithelial neoplasia (CIN) grade 3 or carcinoma in situ (CIS), and 1,218 matched control women. At enrollment participants completed lifestyle questionnaires and provided sera. Subjects were followed-up for a median of 9 years. Immunoassays were used to detect serum antibodies to Human Herpes Virus 2 (HHV-2), Chlamydia trachomatis (CT), Chlamydia pneumoniae, L1 proteins of mucosal and cutaneous HPV types, E6/E7 proteins of HPV16/18, as well as to four polyomaviruses. Adjusted odds ratios (OR) [and 95% confidence intervals (CI)] for CIN3/CIS and ICC risk were respectively: 1.6 (1.2-2.0) and 1.8 (1.1-2.7) for L1 seropositivity to any mucosal HPV type, 1.0 (0.4-2.4) and 7.4 (2.8-19.7) for E6 seropositivity to HPV16/18, 1.3 (0.9-1.9) and 2.3 (1.3-4.1) for CT seropositivity, and 1.4 (1.0-2.0) and 1.5 (0.9-2.6) for HHV-2 seropositivity. The highest OR for ICC was observed for HPV16 E6 seropositivity [OR=10.2 (3.3-31.1)]. Increasing number of sexually transmitted infections (STIs) was associated with increasing risk. Non-STIs were not associated with CC risk. In conclusion, this large prospective study confirms the important role of HPV and a possible contribution of CT and HHV-2 in cervical carcinogenesis. It further identifies HPV16 E6 seropositivity as the strongest marker to predict ICC well before disease development. What's New? Limited data are available from prospective studies concerning the role of past exposure to human papillomavirus (HPV) and other infections in cervical carcinogenesis. This study assessed associations between cervical cancer and pre-cancer and serological markers of exposure to mucosal and cutaneous HPVs, Chlamydia trachomatis (CT), Chlamydia pneumonia, human herpes virus-2 (HHV-2), and polyomaviruses using a nested case-control design within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Associations were found for mucosal HPVs, CT, and HHV-2. A greater number of sexually transmitted diseases further raised the risk of cervical cancer. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cohort study, cervical cancer, HPV, Chlamydia trachomatis, Chlamydia, pneumoniae, human polyomaviruses, HHV-2, EPIC, STI, serology
in
International Journal of Cancer
volume
135
issue
2
pages
440 - 452
publisher
John Wiley & Sons
external identifiers
  • wos:000335460400022
  • scopus:84900037314
ISSN
0020-7136
DOI
10.1002/ijc.28665
language
English
LU publication?
yes
id
b73be3d5-1b09-451e-a990-ed5d27102bc6 (old id 4558713)
date added to LUP
2014-08-01 07:40:39
date last changed
2017-10-22 03:06:54
@article{b73be3d5-1b09-451e-a990-ed5d27102bc6,
  abstract     = {To evaluate prospectively the association between serological markers of selected infections, including HPV, and risk of developing cervical cancer (CC) and precancer, we performed a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study that included 184 cases of invasive CC (ICC), 425 cases of cervical intraepithelial neoplasia (CIN) grade 3 or carcinoma in situ (CIS), and 1,218 matched control women. At enrollment participants completed lifestyle questionnaires and provided sera. Subjects were followed-up for a median of 9 years. Immunoassays were used to detect serum antibodies to Human Herpes Virus 2 (HHV-2), Chlamydia trachomatis (CT), Chlamydia pneumoniae, L1 proteins of mucosal and cutaneous HPV types, E6/E7 proteins of HPV16/18, as well as to four polyomaviruses. Adjusted odds ratios (OR) [and 95% confidence intervals (CI)] for CIN3/CIS and ICC risk were respectively: 1.6 (1.2-2.0) and 1.8 (1.1-2.7) for L1 seropositivity to any mucosal HPV type, 1.0 (0.4-2.4) and 7.4 (2.8-19.7) for E6 seropositivity to HPV16/18, 1.3 (0.9-1.9) and 2.3 (1.3-4.1) for CT seropositivity, and 1.4 (1.0-2.0) and 1.5 (0.9-2.6) for HHV-2 seropositivity. The highest OR for ICC was observed for HPV16 E6 seropositivity [OR=10.2 (3.3-31.1)]. Increasing number of sexually transmitted infections (STIs) was associated with increasing risk. Non-STIs were not associated with CC risk. In conclusion, this large prospective study confirms the important role of HPV and a possible contribution of CT and HHV-2 in cervical carcinogenesis. It further identifies HPV16 E6 seropositivity as the strongest marker to predict ICC well before disease development. What's New? Limited data are available from prospective studies concerning the role of past exposure to human papillomavirus (HPV) and other infections in cervical carcinogenesis. This study assessed associations between cervical cancer and pre-cancer and serological markers of exposure to mucosal and cutaneous HPVs, Chlamydia trachomatis (CT), Chlamydia pneumonia, human herpes virus-2 (HHV-2), and polyomaviruses using a nested case-control design within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Associations were found for mucosal HPVs, CT, and HHV-2. A greater number of sexually transmitted diseases further raised the risk of cervical cancer.},
  author       = {Castellsague, Xavier and Pawlita, Michael and Roura, Esther and Margall, Nuria and Waterboer, Tim and Xavier Bosch, F. and de Sanjose, Silvia and Alberto Gonzalez, Carlos and Dillner, Joakim and Gram, Inger T. and Tjonneland, Anne and Munk, Christian and Pala, Valeria and Palli, Domenico and Khaw, Kay-Tee and Barnabas, Ruanne V. and Overvad, Kim and Clavel-Chapelon, Francoise and Boutron-Ruault, Marie-Christine and Fagherazzi, Guy and Kaaks, Rudolf and Lukanova, Annekatrin and Steffen, Annika and Trichopoulou, Antonia and Trichopoulos, Dimitrios and Klinaki, Eleni and Tumino, Rosario and Sacerdote, Carlotta and Mattiello, Amalia and Bueno-de-Mesquita, H. B. (as) and Peeters, Petra H. and Lund, Eiliv and Weiderpass, Elisabete and Ramon Quiros, J. and Sanchez, Maria-Jose and Navarro, Carmen and Barricarte, Aurelio and Larranaga, Nerea and Ekström, Johanna and Hortlund, Maria and Lindquist, David and Wareham, Nick and Travis, Ruth C. and Rinaldi, Sabina and Tommasino, Massimo and Franceschi, Silvia and Riboli, Elio},
  issn         = {0020-7136},
  keyword      = {cohort study,cervical cancer,HPV,Chlamydia trachomatis,Chlamydia,pneumoniae,human polyomaviruses,HHV-2,EPIC,STI,serology},
  language     = {eng},
  number       = {2},
  pages        = {440--452},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: Evidence from the EPIC cohort},
  url          = {http://dx.doi.org/10.1002/ijc.28665},
  volume       = {135},
  year         = {2014},
}