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J Clin Oncol. 2015 Mar 10;33(8):877-84. doi: 10.1200/JCO.2014.57.8435. Epub 2015 Feb 9.

Human papillomavirus antibodies and future risk of anogenital cancer: a nested case-control study in the European prospective investigation into cancer and nutrition study.

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Aimée R. Kreimer, Krystle A. Lang Kuhs, and Allan Hildesheim, National Cancer Institute, National Institutes of Health, Bethesda, MD; Pagona Lagiou and Dimitrios Trichopoulos, Harvard School of Public Health, Boston, MA; Paul Brennan, Gary Clifford, Silvia Franceschi, and Mattias Johansson, International Agency for Research on Cancer, Lyon; Françoise Clavel-Chapelon, Marie-Christine Boutron-Ruault, and Sylvie Mesrine, Institut National de la Santé et de la Recherche Médicale, Centre for Research in Epidemiology and Population Health; Université Paris Sud; and Institut Gustave Roussy, Villejuif, France; Tim Waterboer, Angelika Michel, Martina Willhauck-Fleckenstein, Renée Turzanski Fortner, Rudolf Kaaks, and Michael Pawlita, German Cancer Research Center, Heidelberg; Heiner Boeing and Annika Steffen, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Elio Riboli, Amanda J. Cross, H. Bas Bueno-de-Mesquita, and Paolo Vineis, School of Public Health, Imperial College, London; Kay-Tee Khaw and Nicholas Wareham, University of Cambridge, Cambridge; Ruth C. Travis, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; Xavier Castellsagué, Institut Català d'Oncologia, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Consorcio de Investigación Biomédica en Red Epidemiología y Salud Pública (CIBERESP), L'Hospitalet de Llobregat; Nerea Larrañaga, María-José Sánchez, Carmen Navarro, and Aurelio Barricarte, Consorcio de Investigación Biomédica en Red Epidemiología y Salud Pública, Madrid; María-José Sánchez, Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria, Hospitales Universitarios de Granada/Universidad de Granada, Granada; Carmen Navarro, Murcia Regional Health Council and Universidad de Murcia, Murcia; Aurelio Barricarte, Navarre Public Health Institute, Pamplona; J. Ramón Quirós, Public Health Directorate, Asturias; Nerea Larrañaga, Basque Regional Healt



Human papillomavirus (HPV) type 16 (HPV16) causes cancer at several anatomic sites. In the European Prospective Investigation Into Cancer and Nutrition study, HPV16 E6 seropositivity was present more than 10 years before oropharyngeal cancer diagnosis and was nearly absent in controls. The current study sought to evaluate the extent to which HPV16 E6 antibodies are present before diagnosis of anogenital cancers within the same cohort.


Four hundred incident anogenital cancers (273 cervical, 24 anal, 67 vulvar, 12 vaginal, and 24 penile cancers) with prediagnostic blood samples (collected on average 3 and 8 years before diagnosis for cervix and noncervix cancers, respectively) and 718 matched controls were included. Plasma was analyzed for antibodies against HPV16 E6 and multiple other HPV proteins and genotypes and evaluated in relation to risk using unconditional logistic regression.


HPV16 E6 seropositivity was present in 29.2% of individuals (seven of 24 individuals) who later developed anal cancer compared with 0.6% of controls (four of 718 controls) who remained cancer free (odds ratio [OR], 75.9; 95% CI, 17.9 to 321). HPV16 E6 seropositivity was less common for cancers of the cervix (3.3%), vagina (8.3%), vulva (1.5%), and penis (8.3%). No associations were seen for non-type 16 HPV E6 antibodies, apart from anti-HPV58 E6 and anal cancer (OR, 6.8; 95% CI, 1.4 to 33.1). HPV16 E6 seropositivity tended to increase in blood samples drawn closer in time to cancer diagnosis.


HPV16 E6 seropositivity is relatively common before diagnosis of anal cancer but rare for other HPV-related anogenital cancers.

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