HUMAN PAPILLOMAVIRUS AND PROGNOSIS OF FEMALE ANOGENITAL CANCER

人乳头瘤病毒与女性肛门生殖器癌的预后

• 批准号: 6102323
• 负责人: STEPHEN M SCHWARTZ
• 金额: --
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-01 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6102323
• 关键词: apoptosis; cancer risk; carcinoma; disease /disorder classification; female; gene expression; genetic markers; histology; hormone receptor; human mortality; human papillomavirus; human subject; interview; neoplasm /cancer invasiveness; neoplasm /cancer relapse /recurrence; oncogenes; polymerase chain reaction; prognosis; rectum neoplasms; tumor suppressor genes; vagina neoplasms; viral carcinogenesis; virus DNA; vulva neoplasms

Although cervical cancer mortality has declined substantially in past decades, the prognosis for the average woman diagnosed with this malignancy has not improved. This may be due in part to the paucity of markers beyond those traditionally employed (e.g., stage, nodal status) that are predictive of prognosis and thus could be used to refine the selection of patients for optimal treatment. This project will test hypotheses regarding the association of selected tumor markers and patient characteristics with the prognosis of invasive cervical carcinoma and other female anogenital carcinomas (vulvar, vaginal, and anal). In particular, we will determine whether the risks of recurrence and/or survival of these neoplasms are related to l) detection of human papillomavirus (HPV) DNA in tumor tissue; 2) serum antibody response to HPV proteins, and 3) patient characteristics. In addition, for cervical carcinoma we will assess the relationship between prognosis and tumor expression of the following markers: p53 tumor suppressor gene and c-myc oncogene products, estrogen and/or progesterone receptors, and measures of tumor cell proliferation (Ki-67 proliferation associated antigen) and apoptosis (bcl-2 oncogene and TdT-mediated dUTP-biotin nick end labeling). These aims will be achieved through a series of tumor site-specific case- cohort studies among all female patients eligible for past and proposed population-based case-control studies of anogenital cancer funded through the Program Project Grant (PPG). From among cohorts of women diagnosed with each anogenital cancer between January 1, 1986 and December 31, 1996, we will 1) identify all deaths and recurrences occurring through 1997, and 2) select a random sample to serve as the comparison sub-cohort. For all cases and sub-cohort members, fixed paraffin-embedded malignant tumor tissue will be obtained, processed, and analyzed in slide-based immunoperoxidase (cervical carcinoma) and PCR studies (all anogenital carcinomas). Information on personal characteristics will be obtained from in-person interviews conducted as part of Project 3, or abstraction of medical records conducted within the scope of this proposal. Proportional hazards models will be used to estimate the relative risk of recurrence and death associated with the factors under study. The results of this investigation have the potential to provide physicians and patients with information that could be used to guide the choice of the most appropriate treatment for anogenital carcinoma among women.

尽管宫颈癌死亡率在过去大幅下降 几十年来，诊断为这种疾病的普通女性的预后 恶性程度并没有改善。这可能部分是由于缺乏 传统使用的标记之外的标记(例如，阶段、节点状态) 可以预测预后，因此可以用来精炼 选择患者进行最佳治疗。该项目将测试 关于选定的肿瘤标志物与患者相关性的假设 浸润性宫颈癌的预后特点及预后 其他女性肛门生殖道癌(外阴、阴道和肛门)。在……里面 特别是，我们将确定复发和/或 这些肿瘤的存活与L)对人类的检测有关 肿瘤组织中的人乳头瘤病毒DNA；2)血清抗体反应 HPV蛋白；3)患者特征。此外，对于宫颈 我们将评估预后与肿瘤的关系 P53、抑癌基因和c-myc的表达 癌基因产物、雌激素和/或孕激素受体以及 肿瘤细胞增殖(Ki-67增殖相关抗原)和 细胞凋亡(bcl2癌基因和TdT介导的dUTP-生物素缺口末端标记)。 这些目标将通过一系列针对肿瘤部位的病例来实现- 所有符合既往和建议治疗条件的女性患者的队列研究 以人群为基础的肛门癌病例对照研究 计划项目拨款(PPG)。从确诊的女性队列中 1986年1月1日至1996年12月31日期间的每一例肛门生殖器癌， 我们将1)确定1997年内发生的所有死亡和复发情况，以及 2)随机抽取一组样本作为比较子队列。为所有人 病例和亚队列成员，固定石蜡包埋恶性肿瘤 将以载玻片为基础获取、处理和分析组织 免疫过氧化物酶(宫颈癌)和聚合酶链式反应(所有肛门 癌症)。有关个人特征的信息将从 作为项目3的一部分进行的面谈，或摘要 在本提案范围内进行的医疗记录。成比例 风险模型将被用来估计复发的相对风险 以及与研究中的因素相关的死亡。这样做的结果 调查有可能为医生和患者提供 可以用来指导选择最合适的信息 女性肛门癌的治疗。