Interaction of EBV and HPV in the Development of Cervical Dysplasia in HIV+ Women

EBV 和 HPV 的相互作用在 HIV 女性宫颈发育不良的发展中

• 批准号: 7780076
• 负责人: MICHAEL E HAGENSEE
• 金额: $ 37.65万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-21 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7780076
• 关键词: Anal canal; Anogenital Human Papilloma Virus Infection; Anogenital cancer; Anus; Archives; Cancer Etiology; Cancerous; Cervical; Cervical dysplasia; Clinical; Data; Detection; Development; Diagnosis; Disease; Dysplasia; Epidemiology; Funding; Goals; HIV; Human Herpesvirus 4; Human Papillomavirus; Individual; Infection; Lead; Lesion; Location; Malignant Neoplasms; Malignant neoplasm of anus; Malignant neoplasm of cervix uteri; Neoplastic Cell Transformation; Oncogenic; Oncogenic Viruses; Pap smear; Pathology; Process; Recovery; Reporting; Research; Risk; Role; Sampling; Secure; Time; Tissue-Specific Gene Expression; Tissues; United States National Institutes of Health; Virus; Woman; cohort; disorder prevention; high risk; public health relevance; spatial relationship

DESCRIPTION (provided by applicant): Human papillomavirus (HPV) infection of anogenital tissues has been implicated as a requisite step in the progression to neoplastic transformation. The role of HPV in cervical cancer has been well elucidated; however, most infections with HPV do not lead to cervical pathology. This leads to the hypothesis that co- factor(s) are present that assist in this process. One of these co-factors that have been elucidated is co- infection with the oncogenic virus, Epstein-Barr (EBV) as HIV+ women co-shedding both HPV and EBV have a 2-4 fold increased risk of cervical pathology. HPV has also been implicated in other anogenital cancers especially anal disease. Both HIV+ and HIV-negative women with cervical disease are also at high risk for developing anal dysplasia and anal cancers related to HPV. The infection rates of the anal canal in HIV+ women are actually higher than cervical but the rates of anal cancer are lower. This implies an even stronger role for co-factor(s) in this process. It has been previously reported that EBV can be detected in anal samples. Preliminary data demonstrates similar detection rates (33%) from archived samples from HIV+ individuals. In addition, anal samples are now being collected from the ongoing longitudinal cohorts of HIV+ and HIV-negative women from New Orleans. Thus, it is hypothesized that EBV is shed from the anus and serves as a co- factor for HPV-related anal disease. If EBV has a similar role in the development of anal cancer as it does in cervical cancer than it follows that: (1) EBV and high oncogenic risk HPV will be present in more anal samples at the time of diagnosis of anal dysplasia than in normal anal tissues (epidemiological relationship), (2) EBV and HPV will be detected in anal samples prior to the development of anal lesions (temporal relationship) and (3) EBV and HPV will be located in diseased anal tissues (spatial relationship). The goal of this competitive revision (NOT-OD-09-058: NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications) is to extend the ongoing study into an examination of the role of EBV in HPV-related anal dysplasia and cancer utilizing the existing clinical cohorts. In addition, anal tissue that will be obtained for pathological diagnosis due to an abnormal anal Pap smear will be examined for the location of EBV and HPV in relation to the anal disease as well as differential gene expression. It is felt that this 2 year proposal will quickly establish a role for EBV in anal dysplasia as well as begin to elucidate the mechanism of interaction between these two oncogenic viruses. These data can then be utilize to secure longer term funding to further explore these interactions at both the clinical (prevention of disease) as well as cellular (mechanism of interaction) level.

描述(由申请人提供)：人类乳头瘤病毒(HPV)感染肛门组织已被认为是肿瘤转化过程中的必要步骤。HPV在宫颈癌中的作用已被很好地阐明；然而，大多数HPV感染不会导致宫颈病理。这导致了一种假设，即辅助因素(S)存在于这一过程中。已阐明的这些共同因素之一是与致癌病毒Epstein-Barr(EBV)的共同感染，因为同时感染HPV和EBV的HIV+女性患宫颈病变的风险增加2-4倍。HPV还与其他肛门生殖道癌，特别是肛门疾病有关。患有宫颈疾病的艾滋病毒阳性和艾滋病毒阴性妇女也有患上与HPV相关的肛门发育不良和肛门癌的高风险。HIV+女性的肛管感染率实际上高于宫颈，但肛门癌的发病率较低。这意味着辅助性因素(S)在这一过程中扮演着更重要的角色。此前有报道称，在肛门样本中可以检测到EBV。初步数据显示，从艾滋病毒携带者的存档样本中获得类似的检测率(33%)。此外，目前正在从新奥尔良HIV+和HIV阴性妇女的纵向队列中收集肛门样本。因此，假设EBV是从肛门排出的，是HPV相关肛门疾病的辅助因素。如果EBV在肛门癌的发生发展中起到与宫颈癌相似的作用，则如下：(1)在确诊为肛门异型增生时，EBV和高致癌风险的HPV将出现在比正常肛门组织中更多的肛门样本中(流行病学关系)，(2)EBV和HPV将在肛门病变发生之前在肛门样本中检测到(时间关系)，(3)EBV和HPV将位于病变的肛门组织中(空间关系)。这项竞争性修订(NOT-OD-09-058：NIH宣布恢复法案资金可用于竞争性修订申请)的目标是利用现有的临床队列将正在进行的研究扩展到EBV在HPV相关性肛门发育不良和癌症中的作用。此外，将对因异常肛门巴氏涂片而获得的用于病理诊断的肛门组织进行EBV和HPV的定位检查，以确定与肛门疾病有关的位置以及差异基因表达。人们认为，这项为期两年的计划将迅速确立EBV在肛门发育不良中的作用，并开始阐明这两种致癌病毒之间的相互作用机制。然后可以利用这些数据来获得长期资金，以便在临床(疾病预防)和细胞(相互作用机制)水平上进一步探索这些相互作用。