BIOMEDICAL COMPUTING SUPPORT FOR THE DIVISION OF CANCER EPIDEMIOLOGY AND GENETIC

癌症流行病学和遗传学领域的生物医学计算支持

• 批准号: 7946108
• 负责人: JANIS A BEACH
• 金额: $ 70万
• 依托单位: INFORMATION MANAGEMENT SERVICES, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-31 至 2010-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7946108
• 关键词: BIOMEDICAL; COMPUTING; SUPPORT; DIVISION; CANCER

Infections with oncogenic types of HPV cause virtually all cases of cervical cancer worldwide. Prophylactic vaccination against HPV 16 and 18, two of the most important HPV types, could protect against a large majority of the cases of cervical cancer globally. Vaccines based on the L1 structural protein of HPV that self-assemble into conformationally-correct virion-like particles (virus-like particles or VLPs) have been shown to be generally safe, immunogenic and effective at preventing precancerous lesions of the cervix associated with HPV-16/18. A community-based Phase 3 randomized controlled trial of an HPV16/18 VLP vaccine is underway in Costa Rica. Costa Rica was chosen for the Phase 3 trial because of our extensive successful scientific collaborations there, the continued high risk of cervical cancer, the universal medical system providing national linkage, and the likelihood of very high participation over the many needed years of close clinical follow-up. Randomization and 3-dose vaccination of 7,466 women enrolled into the HPV-16/18 Vaccine Trial in Costa Rica has been successfully completed. Women have been followed actively on an annual or semi-annual basis since enrollment. Women are now completing their first four years of follow-up in the trial and are being asked to enroll in the extended (up to 10 years) follow-up phase of the study. As women complete four years of active follow-up, cross-over vaccination will be offered to trial participants, as recommended by the trial Data and Safety Monitoring Board (DSMB) and once approved by the Institutional Review Boards (IRBs) overseeing the trial. To date, the trial remains masked. Exploratory analyses are planned and the primary analysis of the prophylactic effect of this vaccine is expected at the end of the first 4-years of follow-up or when sufficient numbers of events occur to warrant evaluation. Evaluation of the therapeutic benefit of this vaccine has been completed. Results from the analysis indicate that the vaccine does not have any effect on clearance of HPV infections, when administered to women who already have an established infection. Thus, the vaccine should not be used to treat established HPV infections or their associated lesions. In support of the vaccine trials, a variety of methodologic and ancillary projects are underway or planned, that will maximize the yield of the main effort. This includes evaluation of immunological correlates of protection, including viral neutralization, total type-specific antibodies, and measures of antibody avidity. Immunological correlates of protection among naturally infected women are being examined and studies are underway to better understand why vaccinated women might be protected against HPV types not included in the vaccine formulation. Several analyses are underway or planned to evaluate the natural history of HPV infection at cervical and other sites and of cervical neoplasia in vaccinated and unvaccinated women.

致癌类型的HPV感染几乎引起了全世界所有宫颈癌的病例。针对HPV 16和18的预防性疫苗接种，这是两种最重要的HPV类型，可以预防全球绝大多数宫颈癌病例。基于HPV的L1结构蛋白的疫苗自我组装成构象校正的病毒体样颗粒（病毒样颗粒或VLP）已被证明通常是安全的，免疫原性的，有效的，可预防与HPV-16/18相关的子宫颈预防性病变。 HPV16/18 VLP疫苗的基于社区的3期随机对照试验正在哥斯达黎加。哥斯达黎加之所以被选为第三阶段试验，是因为我们在那里进行了广泛的成功科学合作，持续的宫颈癌的高风险，普遍医疗系统提供了国家联系，并且在许多经过多年的临床临床随访中，很有可能很高参与。在哥斯达黎加的HPV-16/18疫苗试验中招收的7,466名妇女的随机疫苗接种和3剂量疫苗已成功完成。自入学以来，妇女已每年或半年级积极遵循。妇女现在正在完成试验的前四年随访，并被要求参加该研究的延长（最多10年）的随访阶段。妇女完成四年的积极随访，按照试验数据和安全监测委员会（DSMB）的建议，将向审判参与者提供交叉疫苗接种，并曾经由监督试验的机构审查委员会（IRB）批准。迄今为止，审判仍然被掩盖。计划进行探索性分析，并预计该疫苗的预防作用的主要分析预计在随访的前4年结束时，或者发生足够数量的事件值得评估时。该疫苗的治疗益处的评估已经完成。分析的结果表明，当疫苗对已经具有已建立感染的女性施用时，疫苗对HPV感染的清除没有任何影响。因此，不应使用疫苗来治疗已建立的HPV感染或其相关病变。为了支持疫苗试验，正在进行或计划的各种方法论和辅助项目，这将最大程度地提高主要努力的产量。这包括评估保护的免疫学相关性，包括病毒中和，总类型特异性抗体以及抗体亲和力的度量。正在研究自然感染妇女的免疫学相关性，并正在进行研究，以更好地了解为什么可以保护接种疫苗的妇女免受疫苗配方中未包括的HPV类型。正在进行几项分析或计划评估宫颈和其他部位的HPV感染的自然史以及疫苗接种和未接种疫苗的妇女中的宫颈肿瘤。