EARLY EVENTS IN CLINICAL HUMAN PAPILLOMAVIRUS INFECTION

人乳头瘤病毒(HPV)自然史上的早期事件 感染和类型特异性免疫反应对病毒感染的影响 这些早期感染的结果尚不清楚。具体目标 这项提议的目的是描述一群大学学生中HPV感染的特征 并详细评估以下特异性免疫反应 感染。在连续3年的每一年里，大约550名妇女 在大学卫生诊所寻求常规妇科护理将是 用聚合酶链式反应筛查宫颈HPV感染。那些测试 积极(估计每年200人)将每6个月评估一次 2-4年，届时将提供临床和流行病学信息 收集的和宫颈样本，将通过聚合酶链式反应和 细胞学异常的巴氏涂片检查。对以下项目进行评估 同时感染淋病奈瑟菌、沙眼衣原体、 巨细胞病毒。每次就诊时都会做单纯疱疹。这个 用L1通用引物扩增的标本中HPV的存在将被 用通用探针和25型进行斑点杂交检测 特定的探头。当FCC检测到HPV DNA时。病毒载量将是 使用杂交捕获试验进行了定量。我们将尝试 使用核苷酸区分再感染和再激活或持久性 测序。血液和生殖器分泌物的系列样本将 收集以确定是否存在系统性和局部抗体 HPV-16、18、6和11型衣壳蛋白的病毒样酶联免疫吸附试验 重组病毒感染昆虫细胞产生的颗粒(VLP) 表达相应HPV的L1和1-2基因的杆状病毒。这个 将分析数据以实现以下具体目标：1) 人乳头瘤病毒的发病率和累积患病率的估计 队列妇女中的感染，2)免疫的详细特征 对HPV感染的反应，3)确定HPV基因型的作用， 病毒负担，病毒持久性。局部和系统免疫反应，以及 其他性传播疾病和其他因素的存在 (年龄、吸烟、口服避孕药)对鳞状细胞癌发展的影响 宫颈上皮内病变，以及4)确定是否感染 携带HPV的人对同一类型的再次感染具有免疫力。它是 预计对HPV感染早期事件的了解 将有助于制定预防和控制该病的策略 宫颈癌。

The early events in the natural history of human papillomavirus (HPV) infections and the influence of the type-specific immune response on the outcome of these early infections is not known. The specific objective of this proposal is to characterize HPV infections in a cohort of college women and to evaluate in detail the specific immune response following infection. For each of 3 consecutive years, approximately 550 women seeking routine gynecologic care at a University Health Clinic will be screened for the presence of cervical HPV infection by PCR. Those testing positive (estimated at 200 per year) will be evaluated every 6 months for 2-4 years at which time clinical and epidemiologic information will be collected and cervical specimens,will be examined for HPV DNA by PCR and for cytologic abnormalities by Papanicolaou smear. Evaluation for concurrent infection with Neisseria gonorrhea, Chlamydia trachomatis, cytomegalovirus. and herpes simplex will be performed at each visit. The presence of HPV in specimens amplified with L1 consensus primers will be detected by dot blot hybridization using a generic probe and 25 type specific probes. When HPV DNA is detected by FCC. viral load will be quantified using the hybrid capture assay. Attempts will be made to distinguish reinfection from reactivation or persistence using nucleotide sequencing. Serial samples of blood and genital secretions will be collected to determine the presence of systemic and local antibody to capsid proteins of HPV-16, 18, 6. and 11 by ELISA using virus-like particles (VLP) produced in Insect cells infected with recombinant baculoviruses expressing L1 and 1-2 genes of the respective HPVs. The data will be analyzed to achieve the following specific objectives: 1) estimation of the incidence and cumulative prevalence rates of HPV infection among cohort women, 2) detailed characterization of the immune response to HPV infection, 3) determination of the role of HPV genotype, viral burden, viral persistence. local and systemic immune response, and the presence of other sexually transmitted diseases and other factors (age, smoking, oral contraceptives) on development of squamous intraepithelial lesions of the cervix, and 4) establishing if infection with an HPV results in immunity to reinfection with the same type. It is anticipated that an understanding of the early events of HPV infections will be useful in devising strategies for prevention and control of cervical cancer.