title: Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: evidence from the EPIC cohort.
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.
authors: Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors: Xavier
authors: X
authors: Castellsagué
authors: Michael
authors: M
authors: Pawlita
authors: Esther
authors: E
authors: Roura
authors: Núria
authors: N
authors: Margall
authors: Tim
authors: T
authors: Waterboer
authors: F Xavier
authors: FX
authors: Bosch
authors: Silvia
authors: S
authors: de Sanjosé
authors: Carlos Alberto
authors: CA
authors: Gonzalez
authors: Joakim
authors: J
authors: Dillner
authors: Inger T
authors: IT
authors: Gram
authors: Anne
authors: A
authors: Tjønneland
authors: Christian
authors: C
authors: Munk
authors: Valeria
authors: V
authors: Pala
authors: Domenico
authors: D
authors: Palli
authors: Kay-Tee
authors: KT
authors: Khaw
authors: Ruanne V
authors: RV
authors: Barnabas
authors: Kim
authors: K
authors: Overvad
authors: Françoise
authors: F
authors: Clavel-Chapelon
authors: Marie-Christine
authors: MC
authors: Boutron-Ruault
authors: Guy
authors: G
authors: Fagherazzi
authors: Rudolf
authors: R
authors: Kaaks
authors: Annekatrin
authors: A
authors: Lukanova
authors: Annika
authors: A
authors: Steffen
authors: Antonia
authors: A
authors: Trichopoulou
authors: Dimitrios
authors: D
authors: Trichopoulos
authors: Eleni
authors: E
authors: Klinaki
authors: Rosario
authors: R
authors: Tumino
authors: Carlotta
authors: C
authors: Sacerdote
authors: Amalia
authors: A
authors: Mattiello
authors: H B As
authors: HB
authors: Bueno-de-Mesquita
authors: Petra H
authors: PH
authors: Peeters
authors: Eiliv
authors: E
authors: Lund
authors: Elisabete
authors: E
authors: Weiderpass
authors: J Ramón
authors: JR
authors: Quirós
authors: María-José
authors: MJ
authors: Sánchez
authors: Carmen
authors: C
authors: Navarro
authors: Aurelio
authors: A
authors: Barricarte
authors: Nerea
authors: N
authors: Larrañaga
authors: Johanna
authors: J
authors: Ekström
authors: Maria
authors: M
authors: Hortlund
authors: David
authors: D
authors: Lindquist
authors: Nick
authors: N
authors: Wareham
authors: Ruth C
authors: RC
authors: Travis
authors: Sabina
authors: S
authors: Rinaldi
authors: Massimo
authors: M
authors: Tommasino
authors: Silvia
authors: S
authors: Franceschi
authors: Elio
authors: E
authors: Riboli
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D016022:Case-Control Studies; D002690:Chlamydia Infections / Q000097:blood / Q000150:complications / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D006558:Herpes Genitalis / Q000097:blood / Q000150:complications / Q000453:epidemiology; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000097:blood / Q000150:complications / Q000453:epidemiology; D016036:Seroepidemiologic Studies; D012749:Sexually Transmitted Diseases / Q000097:blood / Q000150:complications* / Q000453:epidemiology; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000382:microbiology*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000097:blood / Q000382:microbiology
chemical_list: D014408:Biomarkers, Tumor
keywords: Chlamydia pneumoniae; Chlamydia trachomatis; EPIC; HHV-2; HPV; STI; cervical cancer; cohort study; human polyomaviruses; serology