Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Department of Infectious Disease Epidemiology, Imperial College London, London, UK.
J Int AIDS Soc. 2018 Jun;21(6):e25110. doi: 10.1002/jia2.25110.
Observational studies suggest HIV and human papillomavirus (HPV) infections may have multiple interactions. We reviewed the strength of the evidence for the influence of HIV on HPV acquisition and clearance, and the influence of HPV on HIV acquisition.
We performed meta-analytic systematic reviews of longitudinal studies of HPV incidence and clearance rate by HIV status (review 1) and of HIV incidence by HPV status (review 2). We pooled relative risk (RR) estimates across studies using random-effect models. I statistics and subgroup analyses were used to quantify heterogeneity across estimates and explore the influence of participant and study characteristics including study quality. Publication bias was examined quantitatively with funnel plots and subgroup analysis, as well as qualitatively.
In review 1, 37 publications (25 independent studies) were included in the meta-analysis. HPV incidence (pooled RR = 1.55, 95% CI: 1.29 to 1.88; heterosexual males: pooled RR = 1.95, 95% CI: 1.62, 2.34; females: pooled RR = 1.63, 95% CI: 1.26 to 2.11; men who have sex with men: pooled RR = 1.36, 95% CI: 1.01 to 1.82) and high-risk HPV incidence (pooled RR = 2.20, 95% CI: 1.90 to 2.54) was approximately doubled among people living with HIV (PLHIV) whereas HPV clearance rate (pooled RR = 0.53, 95% CI: 0.42 to 0.67) was approximately halved. In review 2, 14 publications (11 independent studies) were included in the meta-analysis. HIV incidence was almost doubled (pooled RR = 1.91, 95% CI 1.38 to 2.65) in the presence of prevalent HPV infection. There was more evidence of publication bias in review 2, and somewhat greater risk of confounding in studies included in review 1. There was some evidence that adjustment for key confounders strengthened the associations for review 2. Misclassification bias by HIV/HPV exposure status could also have biased estimates toward the null.
These results provide evidence for synergistic HIV and HPV interactions of clinical and public health relevance. HPV vaccination may directly benefit PLHIV, and help control both HPV and HIV at the population level in high prevalence settings. Our estimates of association are useful for mathematical modelling. Although observational studies can never perfectly control for residual confounding, the evidence presented here lends further support for the presence of biological interactions between HIV and HPV that have a strong plausibility.
观察性研究表明，HIV 和人乳头瘤病毒（HPV）感染可能存在多种相互作用。我们回顾了 HIV 对 HPV 感染和清除的影响，以及 HPV 对 HIV 感染的影响的证据强度。
我们对 HIV 状态下 HPV 发病率和清除率的纵向研究（综述 1）和 HPV 状态下 HIV 发病率的研究（综述 2）进行了荟萃分析系统综述。我们使用随机效应模型对研究中的相对风险（RR）估计值进行了汇总。I 统计量和亚组分析用于量化估计值之间的异质性，并探索参与者和研究特征（包括研究质量）的影响。使用漏斗图和亚组分析以及定性方法定量检查发表偏倚。
在综述 1 中，纳入了 37 篇文献（25 项独立研究）进行荟萃分析。HPV 发病率（汇总 RR=1.55，95%CI：1.29 至 1.88；异性恋男性：汇总 RR=1.95，95%CI：1.62，2.34；女性：汇总 RR=1.63，95%CI：1.26 至 2.11；男男性行为者：汇总 RR=1.36，95%CI：1.01 至 1.82）和高危 HPV 发病率（汇总 RR=2.20，95%CI：1.90 至 2.54）在 HIV 感染者（PLHIV）中增加了近一倍，而 HPV 清除率（汇总 RR=0.53，95%CI：0.42 至 0.67）则减少了近一半。在综述 2 中，纳入了 14 篇文献（11 项独立研究）进行荟萃分析。在存在 HPV 感染的情况下，HIV 发病率几乎增加了一倍（汇总 RR=1.91，95%CI 1.38 至 2.65）。综述 2 中存在更多的发表偏倚证据，而综述 1 中纳入的研究存在更大的混杂风险。有证据表明，调整关键混杂因素可增强综述 2 的相关性。HIV/HPV 暴露状态的分类偏倚也可能使估计值偏向零。
这些结果为具有临床和公共卫生相关性的 HIV 和 HPV 协同相互作用提供了证据。HPV 疫苗接种可能直接使 PLHIV 受益，并有助于在高流行地区控制 HPV 和 HIV。我们的关联估计值可用于数学建模。尽管观察性研究永远无法完全控制残留混杂，但这里提供的证据进一步支持了 HIV 和 HPV 之间存在具有很强合理性的生物学相互作用。
