BackgroundDespite the human papillomavirus (HPV) vaccine being a safe, effective cancer prevention method, its uptake is suboptimal in the United States (U.S.). Previous research has found a variety of intervention strategies (environmental and behavioral) to increase its uptake. The purpose of the study is to systematically review the literature on interventions that promote HPV vaccination from 2015 to 2020.MethodsWe updated a systematic review of interventions to promote HPV vaccine uptake globally. We ran keyword searches in six bibliographic databases. Target audience, design, level of intervention, components and outcomes were abstracted from the full-text articles in Excel databases.ResultsOf the 79 articles, most were conducted in the U.S. (72.2%) and in clinical (40.5%) or school settings (32.9%), and were directed at a single level (76.3%) of the socio-ecological model. Related to the intervention type, most were informational (n= 25, 31.6%) or patient-targeted decision support (n= 23, 29.1%). About 24% were multi-level interventions, with 16 (88.9%) combining two levels. Twenty-seven (33.8%) reported using theory in intervention development. Of those reporting HPV vaccine outcomes, post-intervention vaccine initiation ranged from 5% to 99.2%, while series completion ranged from 6.8% to 93.0%. Facilitators to implementation were the use of patient navigators and user-friendly resources, while barriers included costs, time to implement and difficulties of integrating interventions into the organizational workflow.ConclusionsThere is a strong need to expand the implementation of HPV-vaccine promotion interventions beyond education alone and at a single level of intervention. Development and evaluation of effective strategies and multi-level interventions may increase the uptake of the HPV vaccine among adolescents and young adults.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12889-023-15876-5.