Biomarkers of human papillomavirus (HPV) infection and risk of two increasing cancers

 描述(申请人提供)：人乳头瘤病毒(HPV)感染的生物标志物和两种癌症风险增加摘要口咽癌和肛门癌最近在每年一次的《提交给国家的癌症状况报告》中被强调，因为这两种癌症在美国男性和女性中都在增加。我们的建议集中在这两种癌症上。我们来自欧洲营养与癌症前瞻性调查(EPIC)队列的试点数据表明，在大部分口咽癌患者(35%)中，循环中的HPV16E6抗体在确诊前10年就已经存在，而在对照组中很少见(0.6%)。随后，我们在29%的肛门癌中发现了HPV16E6抗体，在另一组对照中(0.6%)，HPV16E6抗体也是极其罕见的。这些结果值得注意，因为它们表明HPV驱动的肿瘤过程在诊断这两种癌症的许多年前就存在，并提高了HPV16E6抗体可用作高度特异的生物标志物预测癌症发生的可能性。我们已经建立了一个队列联盟，以评估HPV16E6抗体反应在诊断前的敏感性、特异性和真实潜伏期，以及所有检测呈阳性的头颈癌患者的生存结果。通过汇集来自美国和北欧的10个预期队列，这两个人群目前被认为是口咽癌的主要原因，我们计划利用诊断前的血液样本进行分析，识别252例新的口咽癌和180例肛门癌。我们还将收集100例口咽癌和50例肛门癌的肿瘤组织，以评估HPV感染的血清学和肿瘤生物标志物的相关性。

 DESCRIPTION (provided by applicant): Biomarkers of human papillomavirus (HPV) infection and risk of two increasing cancers Summary Oropharyngeal cancer and anal cancer have been recently highlighted in the annual `Report to the Nation on the Status of Cancer' as ebing the two cancers in the US that are increasing among both men and women. Our proposal focuses on these two cancers. Our pilot data from the European Prospective Investigation into Nutrition and Cancer (EPIC) cohort indicate that circulating HPV16 E6 antibodies are present over 10 years before diagnosis in a large proportion of people who develop oropharyngeal cancer (35%), whilst being rare among controls (0.6%). We have subsequently identified HPV16 E6 antibodies in 29% of anal cancers and, again, being extremely rare among a separate group of controls (0.6%). These results are noteworthy as they indicate that a HPV-driven neoplastic process is present many years prior to diagnosis for both of these cancers, and raises the possibility that HPV16 E6 antibodies can be used as a highly specific biomarker to predict cancer onset. We have already established a cohort consortium in order to evaluate the sensitivity, specificity, and true latent period of HPV16 E6 antibody response before diagnosis, as well as survival outcome among all head and neck cancers for those who test positive. By bringing together 10 prospective cohorts from the US and Northern Europe, two populations where HPV infection now being recognized as the predominant cause of oropharynx cancer, we plan to identify 252 new oropharyngeal cancers and 180 anal cancer cases with pre-diagnostic blood samples available for analysis. We will also collect tumor tissue from 100 oropharynx cancer cases and 50 anal cases to evaluate the correlation between serology and tumor biomarkers of HPV infection.