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Project 2

项目2

基本信息

批准号：
8102547
负责人：
BETTY P. DENNIS
金额：
$ 33.74万
依托单位：
DILLARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-16 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8102547
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 Residual state Reverse Transcriptase Polymerase Chain Reaction Risk Role Sampling Screening procedure 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 high risk improved mortality prevent prophylactic 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性传播感染（STI），高危型HPV感染与大多数肛门生殖器恶性肿瘤有关。在世界范围内，hpv相关的子宫颈癌是女性恶性肿瘤的第二大常见原因。在过去的40年里，在美国，宫颈癌的发病率已经大大降低，这被认为是子宫颈抹片检查的结果。发病率明显增加