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

项目总结 全世界有200多万儿童和年轻人在围产期感染艾滋病毒，这些儿童 面临许多不良健康后果的风险，包括宫颈和其他人类乳头瘤病毒的高风险 (HPV)相关癌症。不幸的是，儿科艾滋病毒/艾滋病队列研究，一个丰富的观察性来源 关于围产期感染艾滋病毒儿童的数据，最近发现的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感染 宫颈癌，这一发现需要探索。然而，由于这一群体中的年轻人仍然相对 杨在数据中很难评估接种疫苗对宫颈癌的影响。 我们建议回答有关女孩和年轻妇女宫颈癌预防的关键临床问题 将这一观察数据与经过充分验证的个体水平模拟相结合，研究围产期艾滋病毒感染 宫颈癌模型。我们将根据疫苗的剂量、年龄和HIV来评估疫苗的效力 来自儿科艾滋病毒/艾滋病队列研究数据的接种疫苗时的疾病严重程度。我们将对模拟结果进行校准 队列研究中疫苗效力的模型，并评估估计因果效应所需的假设 这个型号。最后，我们将预测新的疫苗接种策略的影响，例如提早入会年龄。 和额外剂量，对围产期感染艾滋病毒的年轻女性宫颈癌发病率的确定 改变HPV疫苗接种建议是否可以降低这一群体患宫颈癌的风险。 我们的工作将实施和扩展尖端方法，以使用观察性方法模拟随机试验 数据，并将其与模拟模型相结合，以提供快速生成高质量的证据 决策。该项目的成果将改善年轻女性的健康和生活质量 美国和世界范围内围产期艾滋病毒感染情况并展示了一种新的 当随机试验和观察性研究没有足够的数据时估计因果效应的方法 提供以证据为基础的决策。

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.