EARLY EVENTS IN CLINICAL HUMAN PAPILLOMAVIRUS INFECTION

人乳头瘤病毒（HPV）感染的早期症状 感染和类型特异性免疫应答对 这些早期感染的结果尚不清楚。具体目标 这项提案的目的是描述大学生群体中HPV感染的特征， 并详细评估以下特异性免疫反应 感染 连续三年，每年约有550名妇女 在大学健康诊所寻求常规妇科护理将是 通过PCR筛查宫颈HPV感染的存在。这些测试 阳性（估计每年200例）将每6个月进行一次评估， 2-4年，届时临床和流行病学信息将 收集的宫颈标本，将通过PCR检测HPV DNA， 巴氏涂片检查细胞学异常。评价 同时感染淋病奈瑟菌、沙眼衣原体、 巨细胞病毒和单纯疱疹将在每次访视时进行。的 使用L1共有引物扩增的标本中是否存在HPV， 用通用探针和25种 特异性探针当HPV DNA被FCC检测到时。病毒载量将是 使用杂交捕获测定定量。 将试图 使用核苷酸区分再感染与再激活或持续感染 测序血液和生殖器分泌物的系列样本将被 收集以确定全身和局部抗体的存在， HPV-16，18，6的衣壳蛋白。和11通过ELISA使用病毒样 在用重组体感染的昆虫细胞中产生的VLP 表达各HPV的L1和1 - 2基因的杆状病毒。的 将对数据进行分析，以实现以下具体目标：1） 估计HPV的发病率和累积患病率 队列妇女中的感染，2）免疫系统的详细特征 对HPV感染的反应，3）确定HPV基因型的作用， 病毒负荷，病毒持久性。局部和全身免疫反应，以及 其他性传播疾病和其他因素的存在 (age、吸烟、口服避孕药）对鳞状上皮细胞癌的发展 宫颈上皮内病变，以及4）确定是否感染 HPV感染者对同一类型的再次感染具有免疫力。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 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.