Abstract Background Despite the evidence supporting the value of vaccination, Cervical Cancer (CC) and HPV-related diseases still represents a public health challenge, requiring international efforts to address all barriers that can reduce vaccine acceptance and equitable uptake. In this context, implementing interventions aimed at enhancing knowledge levels within target populations emerges as a crucial approach to improve vaccination coverage. Thus, this study conducted within the PERCH project (PartnERship to Contrast HPV), aimed to explore all educational interventions/communication strategies adopted at the international level to improve HPV vaccine uptake. Methods A systematic literature review was conducted by querying three databases from July 1, 2006 (the time of the first HPV vaccine licensure) to January 30, 2024. It included studies focused on educational interventions/communication strategies adopted by healthcare providers (HCPs) targeting the World Health Organization (WHO)-recommended population for HPV vaccination, as well as parents, caregivers, teachers, and other influential individuals involved in vaccination decision-making. Results Overall, 16 studies were considered, with 68.7% (11/16) focusing on educational initiatives and 50% (8/16) on communication strategies. Regarding the target population, 19% (3/16) involved parents/caregivers, 25% (4/16) included both parents and adolescents, and the remaining 56% (9/16) targeted adolescents/young adults. Videos were the most commonly used channel for both types of interventions (54%), followed by informative materials (31%), person-to-person solicitation (17%), social media (15%) and slide presentations (23%). Conclusions Understanding the strengths and weaknesses in HPV knowledge and communication is crucial for developing effective, tailored strategies to disseminate reliable information and promote evidence-based knowledge, thereby implementing high-value healthcare. Key messages • Effective communication of vaccination’s value to stakeholders is essential for informing health policies, guiding best practices, and countering misinformation. • Further research is needed to develop interventions that effectively increase HPV vaccine acceptance, aligning with the WHO’s goals to eliminate CC and HPV-related diseases.