Timing of HPV16-E6 antibody seroconversion before OPSCC: findings from the HPVC3 consortium

作者：A.R. Kreimer, Aida Ferreiro-Iglesias, Mari Nygård, Noemi Bender, L. Schroeder, Allan Hildesheim, Hilary A. Robbins, Michael Pawlita, Hilde Langseth, Nicolas F. Schlecht, Lesley F. Tinker, Ilir Agalliu, Sylvia Smoller, Eivind Ness‐Jensen, Kristian Hveem, Gypsyamber DʼSouza, Kala Visvanathan, Brad May, Giske Ursin, Elisabete Weiderpass, Graham G. Giles, Roger L. Milne, Qingping Cai, W J Blot, Wei Zheng, Stephanie J. Weinstein, Demetrius Albanes, N. Brenner, Judith Hoffman–Bolton, Rudolf Kaaks, Aurelio Barricarte, Anne Tjønneland, Carlotta Sacerdote, Antonia Trichopoulou, Roel Vermeulen, Wen‐Yi Huang, Neal D. Freedman, Paul E. Brennan, Tim Waterboer, Mattias Johansson · 发表于：Annals of Oncology · 年份：2019 · DOI：10.1093/annonc/mdz138 · 被引用次数：93 · 研究领域：Head and Neck Cancer Studies、Cervical Cancer and HPV Research、Salivary Gland Tumors Diagnosis and Treatment

BACKGROUND: Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. PATIENTS AND METHODS: We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). RESULTS: HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1-155.4) in whites and 17.2-fold (95% CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5 years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and <10 years (N = 301 cases) (p-trend < 0.001). Of the 47 HPV16-E6 seropositive cases with ser...