The American Academy of Paediatrics (AAP) divides adolescence into early (12-14 years), middle (15-17 years), and late (18-21 years) stages. School-based HPV educational interventions are largely directed at parents of early adolescents at the time of vaccination. As the average age of first sexual intercourse in high income countries is 15-17 years old, a second educational intervention for middle adolescents could have a strong impact on HPV prevention, providing an opportunity for self-consenting to HPV vaccination in many countries. This paper appraises literature exploring the impact of school-based educational interventions in 15-17 year olds, on HPV vaccination uptake and/or perceptions/knowledge of HPV and its associated cancers. Randomised controlled trials (RCTs) and quasi-experimental designs (QEDs) (2007-2019) were included if they delivered a school-based educational intervention for 15-17 year olds, and the outcome measures included HPV vaccination uptake, knowledge of HPV and associated cancers or perception/attitude regarding self-protection against HPV. Fifteen studies met the inclusion criteria and were assessed for quality using the Quality Assessment Tool for Quantitative Studies. All studies demonstrated a statistically significant improvement in at least one major outcome measure post-intervention, despite the wide range in design of interventions, though only three studies actually measured changes to HPV vaccination uptake. Stakeholder engagement was absent in most intervention designs and many were not grounded in evidenced theory. Content was largely focused on female cervical cancer, rarely discussing oropharyngeal cancer, the most pre-dominant HPV-associated cancer in men. An optimal mixed gender intervention remains to be established for middle adolescents.Copyright © 2020 American Health Foundation. All rights reserved.