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Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: Evidence from the EPIC cohort
Author(s) -
Castellsagué Xavier,
Pawlita Michael,
Roura Esther,
Margall Núria,
Waterboer Tim,
Bosch F. Xavier,
Sanjosé Silvia,
Gonzalez Carlos Alberto,
Dillner Joakim,
Gram Inger T.,
Tjønneland Anne,
Munk Christian,
Pala Valeria,
Palli Domenico,
Khaw KayTee,
Barnabas Ruanne V.,
Overvad Kim,
ClavelChapelon Françoise,
BoutronRuault MarieChristine,
Fagherazzi Guy,
Kaaks Rudolf,
Lukanova Annekatrin,
Steffen Annika,
Trichopoulou Antonia,
Trichopoulos Dimitrios,
Klinaki Eleni,
Tumino Rosario,
Sacerdote Carlotta,
Mattiello Amalia,
BuenodeMesquita H. Bas,
Peeters Petra H.,
Lund Eiliv,
Weiderpass Elisabete,
Quirós J. Ramón,
Sánchez MaríaJosé,
Navarro Carmen,
Barricarte Aurelio,
Larrañaga Nerea,
Ekström Johanna,
Hortlund Maria,
Lindquist David,
Wareham Nick,
Travis Ruth C.,
Rinaldi Sabina,
Tommasino Massimo,
Franceschi Silvia,
Riboli Elio
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28665
Subject(s) - medicine , chlamydia trachomatis , chlamydia , odds ratio , serology , prospective cohort study , cervical cancer , cervical intraepithelial neoplasia , carcinoma in situ , cancer , european prospective investigation into cancer and nutrition , confidence interval , intraepithelial neoplasia , gastroenterology , gynecology , antibody , immunology , prostate cancer
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.