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: 7616766
• 负责人: MICHAEL E HAGENSEE
• 金额: $ 37.05万
• 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/7616766
• 关键词: Anti-Retroviral Agents; Archives; Biopsy; Biopsy Specimen; CD8B1 gene; Cancer Etiology; Cancerous; Cells; Cervical; Cervical dysplasia; Cervix Uteri; Data; Development; Disease; Dysplasia; Epidemiology; Epithelial Cells; Growth; HIV; HPV-High Risk; High Risk Woman; Human; Human Herpesvirus 4; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Immune; Immunity; Infection; Lead; Lesion; Liquid substance; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Methods; Nature; Oncogenic; Oncogenic Viruses; Oncornaviruses; Pilot Projects; Population; Process; Relative (related person); Risk; Risk Factors; Role; Sampling; Sexually Transmitted Diseases; Space Perception; Squamous intraepithelial lesion; Staining method; Stains; T-Lymphocyte; Testing; Tissue Stains; Tissues; Viral; Virus; Woman; cofactor; cohort; cytokine; high risk; improved; insight; prevent; spatial relationship; Anti-Retroviral Agents; Archives; Biopsy; Biopsy Specimen; CD8B1 gene; Cancer Etiology; Cancerous; Cells; Cervical; Cervical dysplasia; Cervix Uteri; Data; Development; Disease; Dysplasia; Epidemiology; Epithelial Cells; Growth; HIV; HPV-High Risk; High Risk Woman; Human; Human Herpesvirus 4; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Immune; Immunity; Infection; Lead; Lesion; Liquid substance; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Methods; Nature; Oncogenic; Oncogenic Viruses; Oncornaviruses; Pilot Projects; Population; Process; Relative (related person); Risk; Risk Factors; Role; Sampling; Sexually Transmitted Diseases; Space Perception; Squamous intraepithelial lesion; Staining method; Stains; T-Lymphocyte; Testing; Tissue Stains; Tissues; Viral; Virus; Woman; cofactor; cohort; cytokine; high risk; improved; insight; prevent; 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. PUBLIC HEALTH RELEVANCE: Human papillomavirus is the cause of most cases of anal cancer; however, most women infected with this virus do not progress to pre-cancer or cancerous lesions implying the need for co-factors in this process. Accumulated evidence points to another cancer-causing virus, Epstein-Barr virus, (EBV), as the potential co- factor, particularly in those women also infected by the HIV virus. The proposed research will further explore the role of EBV in the development HPV-related anal cancer.

描述（由申请人提供）：人乳头瘤病毒（HPV）的肛门生殖组织感染已被视为向肿瘤转化发展的必要步骤。 HPV在宫颈癌中的作用已得到很好的阐明。但是，大多数HPV感染不会导致宫颈病理。这导致了一个假设，即存在协助这一过程的共同因素。这些已阐明的共同因素之一是与致癌病毒（HIV+妇女共同）共同感染的致癌病毒（EBV）共同感染了HPV和EBV，其颈椎病理风险增加了2-4倍。 HPV也与其他肛门生殖器癌有关，尤其是肛门疾病。患有宫颈疾病的HIV+和HIV阴性妇女也对患有肛门发育不良和与HPV相关的肛门癌也有高风险。艾滋病毒+女性肛管的感染率实际上高于宫颈癌，但肛门癌的率较低。这意味着在此过程中，共同因素的作用更加强大。以前据报道，可以在肛门样品中检测到EBV。初步数据表明，来自HIV+个体的存档样品的相似检测率（33％）。此外，现在正在从新奥尔良的HIV+和HIV阴性妇女的纵向人群中收集肛门样本。因此，假设EBV是从肛门中脱离的，并作为HPV相关肛门疾病的共同因素。 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将位于患病的肛门组织中（空间关系）。这项竞争性修订的目的（NOT-OD-09-058：NIH宣布用于竞争性修订应用程序的恢复ACT资金的可用性）是将正在进行的研究扩展到对EBV在HPV相关的肛门异常增生和癌症中利用现有临床队列的癌症的检查。此外，将检查由于异常肛门涂片的病理诊断的肛门组织，将检查EBV和HPV与肛门病以及差异基因表达有关的位置。人们认为，这两年的提案将迅速在肛门发育不良中确立EBV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，以进一步探索临床（预防疾病）以及细胞（相互作用机制）水平的这些相互作用。 公共卫生相关性：人乳头瘤病毒是大多数肛门癌病例的原因；但是，大多数感染该病毒的妇女并没有发展为癌症或癌变病变，这意味着在此过程中需要副因素。积累的证据表明，另一种引起癌症的病毒Epstein-Barr病毒（EBV）是潜在的共同因素，特别是在那些也感染了HIV病毒的妇女中。拟议的研究将进一步探讨EBV在与HPV相关的肛门癌发展中的作用。