Project 2

项目2

• 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
• 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

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），并且大多数肛门生殖器恶性肿瘤涉及高危型HPV感染。在世界范围内，HPV相关的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，美国的宫颈癌发病率大幅下降，这被认为是巴氏涂片筛查的结果。发病率明显增加， 少数民族，服务不足的人群。在美国，非裔美国妇女的宫颈癌发病率比白人妇女高30%，死亡风险增加2倍。这些发现在路易斯安那州更引人注目，非洲裔美国妇女的发病率几乎增加了50%，死亡率比白人妇女增加了3倍。即使在HPV感染率很高的非洲裔美国人中，也有相对较少的妇女进展到宫颈癌。 异常这一事实表明，HPV感染是必要的，但不足以发展宫颈癌。因此，其他辅因子必须增加HPV的致癌潜力。已知的致癌病毒Epstein-Barr病毒（EBV）从宫颈脱落，使其成为HPV相关宫颈发育不良的主要辅助因子候选者。初步数据强烈提示，EBV可能是HPV在宫颈发育不良发病机制中的辅助因子，而与HIV状态无关。据推测，艾滋病毒阴性 从子宫颈同时排出EBV和高危HPV的妇女比仅排出高危HPV的妇女发生子宫颈不典型增生的风险更大。根据这一假设，可以预测：（1）在那些同时脱落EBV和HPV的妇女中，宫颈不典型增生的发生率将增加;（2）在宫颈不典型增生发生之前，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非常接近;（4）对共感染的宫颈组织的分析将有助于发现HPV和EBV的共同脱落。 证明细胞周期控制途径的丧失和细胞凋亡途径的抑制;和（5）预防性HPV疫苗接种将预防这些事件。