Post-Vacc. HPV Genotype Distr. Among HIV+ and HIV- Young Women in S. Africa

描述（由申请人提供）：一个有指导的，以患者为导向的研究项目，旨在为候选人提供严格的培训和经验，研究人乳头瘤病毒（HPV）疫苗引入的病毒学效应。新疫苗对HPV 16型和18型的影响尚不确定。虽然所有宫颈癌都是由HPV引起的，但16型和18型（即疫苗类型）仅占病例的65-70%。另外13-16种HPV类型导致其余30-35%的病例。这项拟议的研究将评估HPV 16/18疫苗对其他致癌HPV类型的影响。 该研究的主要假设是，疫苗和非疫苗HPV类型的流行率将因接种16型和18型疫苗而发生变化。如果得到证实，这将表明非疫苗HPV类型的宫颈癌发病率将在接种疫苗后发生变化。考虑到宫颈癌的惊人全球负担，了解这种新的预防性干预措施如何影响疾病是一个关键的公共卫生问题。拟议的研究将作为欧洲资助的一个更大的南非项目的一个子研究进行。拟议项目的三个具体目标是：1）评估四价HPV疫苗对研究人群中非疫苗HR-HPV分布的影响，2）确定并比较南非HIV感染和未感染HIV的性活跃年轻女性中接种疫苗前后HR-HPV的分布，3）分析研究人群宫颈不典型增生与HPV DNA检测结果的关系。 拟议项目的基本设计是一项纵向队列研究，其中性活跃的年轻女性将接受HPV DNA检测，接种疫苗，然后每隔六个月重新检测HPV。我们的研究人群中的HIV阳性亚组将受到特别关注，因为这种广泛流行的共病可能影响HPV分布和疫苗应答。所有研究受试者的巴氏涂片将在研究入组和退出时进行，以确定HPV感染与宫颈疾病的相关性。 候选人的职业目标包括成为发展中国家传染病预防的独立调查员。执行拟议的项目将准备候选人实现这一目标。 公共卫生相关性：了解针对某些类型的致癌HPV的疫苗接种如何影响许多其他类型的致癌HPV的分布对于预测疫苗接种对减少宫颈癌的影响至关重要。在下一代HPV疫苗的开发过程中，从拟议项目中获得的知识将直接解决这样一个问题：“针对哪种HPV类型的疫苗接种将挽救大多数妇女的生命？".

DESCRIPTION (provided by applicant): A mentored, patient-oriented, research project is proposed to provide the candidate with rigorous training and experience in studying the virologic effects of human papillomavirus (HPV) vaccine introduction. The impact of the new vaccines against HPV types 16 and 18 is uncertain. Although all cervical cancer is caused by HPVs, types 16 and 18 (i.e. the vaccine types) account for only 65-70% of cases. An additional 13-16 HPV types cause the remaining 30-35% of cases. The proposed study will assess the impact of the HPV 16/18 vaccine on the other oncogenic HPV types. The primary hypothesis of the study is that the prevalence of vaccine and non-vaccine HPV types will change as a result of vaccination against types 16 and 18. If confirmed, this would indicate that the incidence of cervical cancer from non-vaccine HPV types will change in the wake of vaccination. Considering the staggering global burden of cervical cancer, understanding how this new preventive intervention impacts the disease is a critical public health concern. The proposed study will be carried out as a sub-study within a larger European-funded project in South Africa. The three specific aims of the proposed project are: 1) To assess the impact of the quadrivalent HPV vaccine on the distribution of non-vaccine HR-HPV in the study population, 2) To determine and compare the pre- and post-vaccination distribution of HR-HPV among HIV-infected and HIV-uninfected sexually active young women in South Africa, and 3) To analyze the association of cervical dysplasia with the results of HPV DNA analysis in the study population. The fundamental design of the proposed project is a longitudinal cohort study in which sexually active young women will be tested for HPV DNA, vaccinated, and then re-tested for HPV at six month intervals. The HIV positive subgroup within our study population will receive special focus as this widely prevalent co-morbidity may effect HPV distribution and vaccine response. Pap smears of all study participants will be performed upon study enrolment and exit to enable correlation of HPV infection with cervical disease. The candidate's career goals include becoming an established, independent investigator of infectious disease prevention in the developing world. Executing the proposed project will prepare the candidate to accomplish this goal. PUBLIC HEALTH RELEVANCE: Project Narrative/Relevance Understanding how vaccination against some types of cancer-causing HPVs affects the distribution of the many other types of cancer-causing HPVs is essential to anticipating the impact of vaccination on reducing cervical cancer. During the development of the next generation of HPV vaccines, knowledge gained from the proposed project will directly address the question, "Vaccination against which HPV types will save the most women's lives?".