Contributions to the literatureOur review synthesizes factors influencing the successful implementation of HPV vaccination programs in SSA in order to improve roll-out and coverage.Our review provides an overview and contextualizes the barriers and facilitators of HPV vaccination implementation in 12 countries in SSA. These span the health care system ranging from personal experiences to economic, social, and political factors.Lessons learnt from past experiences of HPV vaccination in SSA as identified by our review, can contribute to more effective national HPV vaccination programs targeted at eliminating CC and implementing the WHO 90/70/90 triple intervention strategy. BackgroundHuman Papilloma Virus (HPV) is the most common sexually transmitted infection worldwide. Globally, both men and women have a 50% risk of being infected at least once in their life. HPV prevalence is among the highest in sub-Saharan Africa (SSA), at an average of 24%. HPV causes different types of cancers, including cervical cancer (CC), which is the leading cause of cancer deaths among women in SSA. HPV-vaccination has been proven to be effective in reducing HPV induced cancers. SSA countries are delayed in reaching the WHO's target of fully vaccinating 90% of girls within the age of 15 by 2030. Our systematic review aims to identify barriers and facilitators of HPV-vaccination in SSA to inform national implementation strategies in the region.MethodsThis is a mixed method systematic review based on the PRISMA statement and The Joanna Briggs Institute Reviewers' Manual. Search strategies were adapted to each selected database: PubMed/MEDLINE, Livivo, Google Scholar, Science Direct, and African Journals Online for papers published in English, Italian, German, French and Spanish between 1 December 2011 and 31 December 2021. Zotero and Rayyan were the software used for data management. The appraisal was conducted by three independent reviewers.ResultsA total of 20 articles were selected for appraisal from an initial 536 articles. Barriers included: limited health system capacities, socio-economic status, stigma, fear and costs of vaccines, negative experience with vaccinations, COVID-19 pandemic, lack of correct information, health education (HE) and consent. Additionally, we found that boys are scarcely considered for HPV-vaccination by parents and stakeholders. Facilitators included: information and knowledge, policy implementation, positive experience with vaccinations, HE, stakeholders' engagement, women's empowerment, community engagement, seasonality, and target-oriented vaccination campaigns.ConclusionsThis review synthesizes barriers and facilitators of HPV-vaccinations in SSA. Addressing these can contribute to the implementation of more effective HPV immunization programs targeted at eliminating CC in line with the WHO 90/70/90 strategy.Registration and fundingProtocol ID: CRD42022338609 registered in the International Prospective Register of Systematic Reviews (PROSPERO). Partial funds: German Centre for Infection research (DZIF) project NAMASTE: 8,008,803,819.