Project 2

项目2

基本信息

批准号：
8434770
负责人：
BETTY P. DENNIS
金额：
$ 12.19万
依托单位：
DILLARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-03-05 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8434770
关键词：
African American Antibodies Apoptosis Biopsy Cancer cell line Caucasians Caucasoid Race Cell Cycle Cell Cycle Regulation Cell physiology Cells Cervical Cervical dysplasia Cervix Uteri Clinic Clinical Cloning Collection Colposcopy Conization Data Development Diagnostic Disease Dysplasia Employee Strikes Enrollment Epithelial Cells Epithelium Event Gardasil Genes HIV HPV-High Risk High Risk Woman Human Herpesvirus 4 Human Papillomavirus Human papilloma virus infection Human papillomavirus 16 Human papillomavirus 6 Hysterectomy Immune response Immunosuppression In Vitro Incidence Individual Infection Inhibition of Apoptosis Lead Liquid substance Location Longitudinal Studies Loop electrosurgical excision procedure Louisiana Malignant Neoplasms Malignant neoplasm of cervix uteri Masks Medical center Microarray Analysis Minority Normal tissue morphology Oncogenic Oncogenic Viruses Pap smear Pathogenesis Pathway interactions Phase Population Prevention Procedures Process Research Residual state Reverse Transcriptase Polymerase Chain Reaction Risk Role Sampling Serological Serum Sexually Transmitted Diseases Squamous intraepithelial lesion Staining method Stains Testing Therapeutic Tissues Underrepresented Minority Underserved Population United States Vaccination Vaccines Viral Woman carcinogenesis cofactor cohort health disparity high risk improved minority health mortality prevent prophylactic screening spatial relationship vaccine efficacy

项目摘要

Human papillomavirus (HPV) infection is the most common viral sexually transmitted infection (STI), and infection with high-risk types of HPV has been implicated in the majority of anogenital malignancies. Worldwide, HPV-related cervical cancer is the second most common cause of malignancy in women. Over the past 40 years in the United States, cervical cancer incidence rates have been dramatically reduced, which is believed to be the result of Pap smear screening. Incidence rates are distinctly increased in minority, underserved populations. In the United States, African American women have 30% higher incidence of cervical cancer and a 2-fold increased risk of mortality as compared to Caucasian women. These findings are more striking in Louisiana, where African American women have almost a 50% increase in incidence and a 3-fold increase in mortality over their Caucasian counterparts. Even in the African-American population, where HPV infection rates are high, relatively few women progress to cervical abnormalities. This fact indicates that HPV infection is necessary but not sufficient for the development of cervical cancer. Thus, other cofactors must augment the oncogenic potential of HPV. The known oncogenic virus, Epstein-Barr virus (EBV), is shed from the cervix, making this a prime co-factor candidate for HPV-related cervical dysplasia. Preliminary data strongly suggest that EBV may be a co-factor to HPV in the pathogenesis of cervical dysplasia, irrespective of HIV status. It is hypothesized that HIV-negative women who shed both EBV and high-risk HPV from their cervix are at greater risk for cervical dysplasia than women who shed only high-risk HPV. From this hypothesis, it is predicted that (1) the rate of cervical dysplasia will be increased in those women co-shedding both EBV and HPV; (2) EBV and HPV cervical shedding will be detected prior to the development of cervical dysplasia; (3) EBV and HPV will be located in the same cervical epithelial cells or in close proximity; (4) analysis of co-infected cervical tissue will demonstrate loss of cell cycle control pathways and inhibition of apoptosis pathways; and (5) prophylactic HPV vaccination will prevent these events.

人乳头瘤病毒（HPV）感染是最常见的病毒性传播感染（STI），而具有高危HPV的感染已与大多数肛门生物恶性肿瘤有关。在全球范围内，与HPV相关的宫颈癌是女性恶性肿瘤的第二大最常见原因。在过去的40年中，在美国，宫颈癌的发病率已大大降低，这被认为是PAP涂片筛查的结果。发病率明显提高少数人服务不足的人口。在美国，与高加索妇女相比，非洲裔美国妇女的宫颈癌发病率更高30％，死亡风险增加了2倍。这些发现在路易斯安那州更加惊人，在那里，非裔美国妇女的发病率将近50％，死亡率比高加索同行的死亡率增加了3倍。即使在HPV感染率很高的非裔美国人人口中，相对较少的妇女发展为宫颈异常。这一事实表明，HPV感染是必要的，但对于宫颈癌的发展不足。因此，其他辅助因子必须增强HPV的致癌潜力。已知的致癌病毒Epstein-Barr病毒（EBV）是从子宫颈脱离的，使其成为HPV相关宫颈发育不良的主要辅助因子候选者。初步数据强烈表明，在宫颈发育不良的发病机理中，EBV可能是HPV的共同因素，而与HIV状态无关。假设HIV阴性与仅脱落高风险HPV的妇女相比，从子宫颈发出EBV和高风险HPV的女性对宫颈发育不良的风险更大。从这一假设中可以预测，（1）在EBV和HPV共同塑造的妇女中，宫颈发育不良率将增加；（2）在宫颈发育不良发展之前，将检测到EBV和HPV宫颈脱落；（3）EBV和HPV将位于相同的宫颈上皮细胞中或近距离近端；（4）分析共感染的宫颈组织将证明细胞周期控制途径的丧失和抑制凋亡途径；（5）预防性HPV疫苗接种将防止这些事件。