Real-world impact and effectiveness assessment of the quadrivalent HPV vaccine: a systematic review of study designs and data sources

Vaccine effectiveness and impact studies are typically observational, generating evidence after vaccine launch in a real-world setting. For human papillomavirus (HPV) vaccination studies, the variety of data sources and methods used is pronounced. Careful selection of study design, data capture and analytical methods can mitigate potential bias in such studies.
We systematically reviewed the different study designs, methods, and data sources in published evidence (1/2007–3/2020), which assessed the quadrivalent HPV vaccine effectiveness and impact on cervical/cervicovaginal, anal, and oral HPV infections, anogenital warts, lesions in anus, cervix, oropharynx, penis, vagina or vulva, and recurrent respiratory papillomatosis.
The rapid growth in access to real-world data allows global monitoring of effects of different public health interventions, including HPV vaccination programs. But the use of data which are not collected or organized to support research also underscore a need to develop robust methodology that provides insight of vaccine effects and consequences of different health policy decisions. To achieve the WHO elimination goal, we foresee a growing need to evaluate HPV vaccination programs globally. A critical appraisal summary of methodology used will provide timely guidance to researchers who want to initiate research activities in various settings.

疫苗有效性与影响研究通常属于观察性研究，在疫苗上市后的真实世界环境中生成相关证据。针对人乳头瘤病毒（Human Papillomavirus, HPV）疫苗接种研究而言，其所采用的数据源与研究方法类型多样。审慎选择研究设计、数据采集与分析方案，可有效减轻此类研究中潜在的偏倚风险。
本研究对2007年1月至2020年3月期间已发表的相关证据进行了系统综述，涵盖了评估四价HPV疫苗有效性，及其对宫颈/宫颈阴道、肛门与口腔HPV感染、肛门生殖器疣、肛门、宫颈、口咽、阴茎、阴道或外阴部位病变，以及复发性呼吸道乳头状瘤病的影响所采用的各类研究设计、方法与数据源。
真实世界数据获取渠道的快速拓展，使得全球范围内能够对包括HPV疫苗接种项目在内的各类公共卫生干预措施的效果开展监测。但由于此类数据并非为支持科研而专门采集或整理，因此亟需开发稳健的研究方法学，以明晰疫苗效应与不同卫生政策决策所产生的后果。为实现世界卫生组织（World Health Organization, WHO）的消除目标，我们预计全球范围内针对HPV疫苗接种项目开展评估的需求将持续增长。对所采用的方法学进行批判性评价综述，将为有意在各类场景中启动相关研究的科研人员提供及时的指导。