BIOMEDICAL COMPUTING SUPPORT FOR THE DIVISION OF CANCER EPIDEMIOLOGY AND GENETIC

感染致癌类型的HPV几乎导致了全世界所有的宫颈癌病例。预防性接种HPV16和HPV18型是最重要的两种HPV类型，可以预防全球绝大多数宫颈癌病例。基于HPV的L1结构蛋白的疫苗自组装成构象正确的病毒颗粒(病毒样颗粒或VLP)已被证明总体上是安全的、具有免疫原性的，在预防与HPV-16/18相关的宫颈癌前病变方面有效。一项基于社区的HPV16/18VLP疫苗的第三阶段随机对照试验正在哥斯达黎加进行。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的科学合作，宫颈癌的风险仍然很高，提供国家联系的全民医疗系统，以及在所需的多年密切临床随访中参与的可能性非常高。在哥斯达黎加参加HPV-16/18疫苗试验的7466名妇女的随机和三剂疫苗接种工作已经顺利完成。自注册以来，每年或每半年积极跟踪妇女一次。女性现在正在完成她们在试验中的头四年跟踪调查，并被要求参加这项研究的延长(最多10年)后续阶段。随着妇女完成四年的积极跟踪，将按照试验数据和安全监测委员会(DSMB)的建议并一旦获得监督试验的机构审查委员会(IRBs)的批准，向试验参与者提供交叉疫苗接种。到目前为止，审判仍然是蒙在鼓里的。计划进行探索性分析，预计在头4年随访结束时或在发生足够数量的事件需要进行评估时，对该疫苗的预防效果进行初步分析。对该疫苗的治疗效益的评估已经完成。分析结果表明，当疫苗接种于已确诊感染的妇女时，对清除HPV感染没有任何影响。因此，疫苗不应用于治疗已确诊的HPV感染或与其相关的病变。为了支持疫苗试验，正在进行或计划进行各种方法和辅助项目，以最大限度地提高主要工作的产量。这包括评估保护性的免疫学相关性，包括病毒中和、总类型特异性抗体和抗体亲和力的测量。正在审查自然感染妇女中保护的免疫学相关性，并正在进行研究，以更好地了解为什么接种疫苗的妇女可能会受到保护，使其免受疫苗配方中未包括的HPV类型的影响。正在进行或计划进行一些分析，以评估宫颈和其他部位的HPV感染以及接种疫苗和未接种疫苗的妇女宫颈肿瘤的自然病史。

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.