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

 描述（由申请人提供）：人乳头瘤病毒（HPV）感染的生物标志物和两种增加的癌症风险摘要口咽癌和肛门癌最近在年度“国家癌症状况报告”中被强调为美国男性和女性中增加的两种癌症。我们的建议主要针对这两种癌症。我们来自欧洲营养与癌症前瞻性调查（EPIC）队列的初步数据表明，在诊断前10年内，大部分患有口咽癌的人（35%）中存在循环HPV 16 E6抗体，而对照组中则很少见（0.6%）。随后，我们在29%的肛门癌中发现了HPV 16 E6抗体，并且在另一组对照组中（0.6%）非常罕见。这些结果值得注意，因为它们表明HPV驱动的肿瘤过程在这两种癌症的诊断前多年就存在，并提高了HPV 16 E6抗体可用作高度特异性生物标志物来预测癌症发作的可能性。我们已经建立了一个队列联盟，以评估诊断前HPV 16 E6抗体反应的敏感性，特异性和真实潜伏期，以及所有头颈部癌症中检测阳性者的生存结局。通过汇集来自美国和北方的10个前瞻性队列，这两个人群HPV感染现在被认为是口咽癌的主要原因，我们计划确定252例新的口咽癌和180例肛门癌病例，并提供诊断前血液样本进行分析。我们还将收集100例口咽癌病例和50例肛门病例的肿瘤组织，以评估HPV感染的血清学和肿瘤生物标志物之间的相关性。

 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.