HPV vaccination efficacy for cervical cancer prevention in young women with perinatal HIV infection

项目摘要 全世界有200多万儿童和年轻人在围产期感染了艾滋病毒，这些儿童 有许多不良健康后果的风险，包括宫颈和其他人乳头瘤病毒的高风险 （HPV）相关的癌症。不幸的是，儿科艾滋病毒/艾滋病队列研究，一个丰富的观察来源， 关于围产期艾滋病毒感染儿童的数据，最近发现令人不安的证据表明， HPV疫苗在围产期HIV感染儿童中的应用鉴于感染艾滋病毒的妇女和女孩极易受到 宫颈癌，这一发现需要探讨。然而，由于这一群体中的年轻人仍然相对 年轻人评估接种疫苗对宫颈癌的影响的数据是困难的。 我们建议回答关于预防女孩和年轻妇女宫颈癌的关键临床问题， 围产期艾滋病毒感染，结合这一观察数据与一个良好的验证个人水平的模拟 子宫颈癌的模型。我们将根据接种次数、年龄和艾滋病毒来估计疫苗的效力 来自儿科HIV/AIDS队列研究数据的疫苗接种时疾病严重程度。我们将校准模拟 在队列研究中建立疫苗有效性模型，并评估估计因果效应所需的假设， 该模型最后，我们将预测新的疫苗接种策略的影响，如早期接种年龄 和额外剂量，对围产期感染艾滋病毒的年轻妇女宫颈癌发病率的影响，以确定 改变HPV疫苗接种的建议是否可以降低该组的宫颈癌风险。 我们的工作将实施和扩展尖端的方法，以模拟随机试验，使用观察 数据并将其与仿真模型联合收割机相结合，以快速生成高质量的证据， 决策的该项目的成果将改善年轻妇女的健康和生活质量， 围产期艾滋病毒感染在美国和世界各地，并证明了一种新的实施 当随机试验和观察性研究的数据不足以 提供基于证据的决策。

PROJECT SUMMARY Over 2 million children and young adults worldwide were perinatally infected with HIV, and these children are at risk of many adverse health outcomes, including a high risk of cervical and other human papillomavirus (HPV)-associated cancers. Unfortunately, the Pediatric HIV/AIDS Cohort Study, a rich source of observational data on children with perinatal HIV infection, recently found troubling evidence that suggests low efficacy of the HPV vaccine in children with perinatal HIV infection. Given the high vulnerability of women and girls with HIV to cervical cancer, this finding needs to be explored. However, since the youth in this cohort are still relatively young assessing the impact of vaccination on cervical cancer in the data is difficult. We propose to answer key clinical questions about cervical cancer prevention in girls and young women with perinatal HIV infection by combining this observational data with a well-validated individual-level simulation model of cervical cancer. We will estimate the vaccine efficacy based on number of doses, age, and HIV disease severity at vaccination from the Pediatric HIV/AIDS Cohort Study data. We will calibrate the simulation model to vaccine efficacy in the cohort study, and assess assumptions required to estimate causal effects from this model. Finally, we will project the impact of novel vaccination strategies, such as earlier age at initiation and additional doses, on cervical cancer incidence in young women with perinatal HIV infection to determine whether altering the recommendations for HPV vaccination can reduce cervical cancer risk in this group. Our work will implement and extend cutting-edge approaches to emulate randomized trials using observational data and combine this with simulation models to provide rapid generation of high-quality evidence to inform decision-making. The results of this project will improve the health and quality of life of young women with perinatal HIV-infection in the United States and worldwide and demonstrate the implementation of a novel method for estimating causal effects when randomized trials and observational studies have insufficient data to provide evidence-based decision-making.