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感染几乎导致全世界所有宫颈癌病例。预防性接种HPV 16和18（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，其自组装成构象正确的病毒体样颗粒（病毒样颗粒或VLP），已经显示出通常是安全的、免疫原性的，并且有效预防与HPV-16/18相关的宫颈癌前病变。哥斯达黎加正在进行一项以社区为基础的HPV 16/18 VLP疫苗的3期随机对照试验。选择哥斯达黎加进行3期试验是因为我们在那里进行了广泛成功的科学合作，宫颈癌的持续高风险，提供国家联系的全民医疗系统，以及在需要多年密切临床随访的情况下参与率很高的可能性。哥斯达黎加HPV-16/18疫苗试验的7 466名妇女的随机化和3剂疫苗接种已成功完成。自入组以来，每年或每半年对妇女进行一次积极随访。女性现在正在完成他们在试验中的前四年随访，并被要求参加研究的延长（长达10年）随访阶段。当女性完成四年的积极随访时，将根据试验数据和安全监测委员会（DSMB）的建议，并在监督试验的机构审查委员会（IRB）批准后，向试验参与者提供交叉疫苗接种。到目前为止，审判仍然是秘密进行的。计划进行探索性分析，预计在前4年随访结束时或发生足够数量的事件以保证评价时，对该疫苗的预防作用进行主要分析。该疫苗的治疗获益评价已完成。分析结果表明，当对已经感染的妇女接种疫苗时，疫苗对HPV感染的清除没有任何影响。因此，该疫苗不应用于治疗已确定的HPV感染或其相关病变。为了支持疫苗试验，正在进行或计划进行各种方法学和辅助项目，以最大限度地提高主要工作的产量。这包括评价保护的免疫学相关性，包括病毒中和、总类型特异性抗体和抗体亲合力的测量。自然感染妇女的免疫保护相关性正在研究中，研究正在进行中，以更好地了解为什么接种疫苗的妇女可能会受到保护，免受疫苗配方中不包括的HPV类型的影响。正在进行或计划进行几项分析，以评估接种疫苗和未接种疫苗的妇女宫颈和其他部位HPV感染的自然史以及宫颈肿瘤的自然史。