Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: Evidence from the EPIC cohort
2014 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 2, 440-452 p.Article in journal (Refereed) Published
To evaluate prospectively the association between serological markers of selected infections, including HPV, and risk of developing cervical cancer (CC) and pre-cancer, 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.
Place, publisher, year, edition, pages
Wiley-Blackwell, 2014. Vol. 135, no 2, 440-452 p.
cohort study, cervical cancer, HPV, Chlamydia trachomatis, Chlamydia pneumoniae, human polyomaviruses, HHV-2; EPIC, STI, serology
Cancer and Oncology
IdentifiersURN: urn:nbn:se:umu:diva-84250DOI: 10.1002/ijc.28665ISI: 000335460400022PubMedID: 24338606OAI: oai:DiVA.org:umu-84250DiVA: diva2:681170