HUMAN PAPILLOMAVIRUS AND PROGNOSIS OF FEMALE ANOGENITAL CANCER

虽然子宫颈癌死亡率在过去已大幅下降， 几十年来，被诊断患有这种疾病的普通女性的预后 恶性肿瘤没有改善。这可能部分是由于缺乏 传统上使用的标记之外的标记（例如，阶段，节点状态） 可以预测预后，因此可以用来改善 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 浸润性宫颈癌的临床特征与预后的关系， 其他女性肛门生殖器癌（外阴、阴道和肛门）。在 特别是，我们将确定是否复发的风险和/或 这些肿瘤存活率与l）人类 肿瘤组织中的乳头状瘤病毒（HPV）DNA; 2）血清抗体反应， HPV蛋白，和3）患者特征。此外，对于宫颈 我们将评估预后与肿瘤的关系 以下标志物的表达：p53肿瘤抑制基因和c-myc 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 凋亡（bcl-2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肿瘤部位特异性病例来实现， 在所有符合既往和拟定研究条件的女性患者中开展的队列研究 基于人群的肛门生殖器癌病例对照研究， 计划项目补助金（PPG）从被诊断为 在1986年1月1日至1996年12月31日期间， 我们将1）确定1997年发生的所有死亡和复发， 2)选择随机样本作为比较子队列。为所有 例和子队列成员，固定石蜡包埋恶性肿瘤 将在基于切片的组织中获取、处理和分析 免疫过氧化物酶（宫颈癌）和PCR研究（所有肛门生殖器 癌）。有关个人特征的资料，可从 作为项目3的一部分进行的面对面访谈，或 在本提案范围内进行的医疗记录。比例 风险模型将用于估计复发的相对风险 和死亡与所研究的因素有关。 的结果 调查有可能为医生和患者提供 可用于指导选择最适当的 治疗女性肛门生殖器癌。

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.