EPIDEMIOLOGY OF HPV16/18 VARIANTS IN CERVICAL NEOPLASIA

HPV16/18 变种在宫颈肿瘤中的流行病学

• 批准号: 6377700
• 负责人: LONG FU XI
• 金额: $ 27.46万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-11 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6377700
• 关键词: cervix neoplasms; clinical research; epidemiology; female; human papillomavirus; human subject; nucleic acid sequence; polymerase chain reaction; virus DNA; virus classification; women's health

DESCRIPTION (Adapted from applicant's abstract): Human papillomaviruses (HPVs) are classified into "types," "subtypes," and variants." HPV16 and 18 are types known to be central to the pathogenesis of most invasive cervical cancers (ICC) and their precursor lesion, cervical intraepithelial neoplasia (CIN) grade 2-3. However, many women acquire and spontaneously resolve cervical infections with these HPV types. We hypothesize that certain HPV 1 6 and 18 variants differ in their biologic behavior and risk of cervical neoplasia. A number of small studies have examined associations between HPV 1 6 and 18 variants and risk of cervical neoplasia and many, but not all, suggest differences in biologic behaviors. Confirmation of these findings in large, more representative populations is essential. We propose to efficiently examine these issues by performing additional assays on a subset of samples collected during the ongoing NCI-sponsored, multi-center randomized clinical trial: ASCUS/LSIL Triage Study (ALTS). This study, which includes 5,086 women from four different regions of the country, is examining how to best manage women referred with a cytologic diagnosis of atypical squamous cells of uncertain significance (ASCUS) or low- grade squamous intraepithelial lesions (LSIL) of the cervix. The ALTS dataset is extremely rich with results from standardized collection and testing of clinical specimens, detailed questionnaires with information on potential confounders, and histologic and colposcopic diagnoses provided by expert panel review. By including data from only those women enrolled in the immediate colposcopy arm of ALTS, we will develop precise estimates of the association between HPV 1 6 and IS variants and cervical neoplasia (aims 1 and 2), and determine whether those variants that are associated with CIN 2-3 have increased DNA levels or specific nucleotide changes in the LCR and E6 regions of the genome (aim 4). Furthermore, using data from women enrolled in the immediate colposcopy and conservative management arms, we will provide the first observations on the relationship between HPV 1 6 variants and risk for recurrence after treatment for CIN 2-3 (aim 3). To address these aims, we will perform PCR-based assays for detection and typing of 7,290 samples, classify (by DNA sequencing) HPV variants present in samples from women infected with HPV16 (n=548) or 18 (n=222), and quantify (by a PCR-based kinetic thermocycling assay) the amount of HPV DNA present in the 1,915 HPV16-positive and 222 HPV18-positive samples. The proposed study is likely to make important contributions to our understanding of the role of HPV 16 and 18 variants in the pathogenesis of cervical cancer.

描述（改编自申请人的摘要）：人乳头瘤病毒（HPV） 被分类为“类型”，“亚型”和变体。“ HPV16和18是类型 已知是大多数侵入性宫颈癌（ICC）的发病机理的核心 及其前体病变，颈椎上皮肿瘤（CIN）2-3级。 但是，许多妇女获得并自发解决了宫颈感染 这些HPV类型。我们假设某些HPV 1 6和18变体不同 它们的生物行为和宫颈肿瘤的风险。许多小 研究检查了HPV 1 6和18变体之间的关联和 宫颈肿瘤和许多（但不是全部）都暗示了生物学的差异 行为。确认这些发现的大型，更有代表性 人口至关重要。我们建议通过 对在收集的样品子集中进行其他测定 正在进行的NCI赞助的多中心随机临床试验：ASCUS/LSIL 分诊研究（ALTS）。这项研究，其中包括来自四个不同不同的5,086名女性 该国地区正在研究如何最好地管理以 具有不确定意义的非典型鳞状细胞的细胞学诊断 （Ascus）或低级鳞状上皮内病变（LSIL）的子宫颈。 ALTS数据集非常丰富，并获得了标准化集合的结果 以及临床标本的测试，详细的问卷以及有关信息的信息 潜在的混杂因素以及组织学和阴道镜诊断 专家小组评论。通过仅包括来自那些入学的妇女的数据 ALTS的即时阴道镜检查部门，我们将制定对 HPV 1 6与变体和宫颈肿瘤之间的关联（目标1和 2），确定与CIN 2-3相关的那些变体是否具有 LCR和E6区域的DNA水平增加或特定的核苷酸变化 基因组（目标4）。此外，使用来自该女性的数据 立即进行阴道镜检查和保守管理部门，我们将提供 首先观察到HPV 1 6变体之间的关系和风险 CIN 2-3治疗后的复发（AIM 3）。为了解决这些目标，我们将 执行基于PCR的测定法以检测和键入7,290个样品，分类 （通过DNA测序）来自感染的女性的样品中的HPV变体 HPV16（n = 548）或18（n = 222），并量化（通过基于PCR的动力学热环节 测定）1,915 HPV16阳性和222中存在的HPV DNA量 HPV18阳性样品。拟议的研究很可能很重要 我们对HPV 16和18变体在中的作用的理解做出的贡献 宫颈癌的发病机理。