ABSTRACT/SUMMARY Cervical cancer is the leading cause of cancer death in Zambia, where HIV prevalence is also high (11.3%). HIV heightens the risk of developing and dying from cervical cancer. The human papillomavirus (HPV) vaccine is a WHO-endorsed, evidence-based tool that can prevent 90% of cervical cancers, and is recommended for girls ages 9-14. However, HPV vaccine coverage is low (16%) in low- and middle- income countries (LMICs), and our team's on-the-ground experience suggests HPV vaccination is even lower in Zambia, particularly among girls with HIV, who are most at risk of poor cancer outcomes. Currently, HPV vaccination is delivered via school-based campaigns, which are viewed as efficient for broad coverage but also exclude the most vulnerable children—those out-of-school or who irregularly attend (e.g., orphans, poor). Adolescents living with HIV (ALHIV) are more likely to have these additional vulnerabilities. In addition, WHO recommends ALHIV receive a 3rd dose of the HPV vaccine, which is not given in traditional 2-dose school-based campaigns. To ensure that ALHIV have access to the WHO-recommended 3-doses, we propose to integrate HPV vaccination into routine care in adolescent HIV clinics. Adolescent HIV clinics in Zambia have regular contact with ALHIV and are trusted sources of health information for the community. Given the known challenges of providing cervical cancer prevention in LMICs, including Zambia (e.g., stigma, misinformation, staffing, supply chain), integrating HPV vaccination requires a multilevel approach, stakeholder engagement, and diversified implementation strategies. To achieve success, we will co-design a package of implementation strategies using a previously successful implementation research approach developed for cervical cancer prevention in LMICs: the Integrative Systems Praxis for Implementation Research (INSPIRE). INSPIRE is a novel, formal, and comprehensive framework to develop, implement, and evaluate implementation science efforts. Following key elements of INSPIRE, our specific aims are to: 1) Identify the unique multilevel contextual factors (barriers and facilitators) across HIV settings (rural, urban, peri-urban) that influence HPV vaccine uptake; 2) Use Implementation Mapping to translate stakeholder feedback and findings from Aim 1 into a package of implementation strategies to integrate HPV vaccine into HIV clinics; 3) Conduct a Hybrid Type 3 effectiveness-implementation trial to evaluate the package of multilevel implementation strategies for integrating HPV vaccine into HIV clinics. Our research team has significant expertise in HIV, HPV, cancer prevention, implementation science, and LMIC research. Wehave strong institutional backing, including$325,000 over the course of the study;strong support, technical expertise, and resources (e.g., vaccines) from the Zambian Ministry of Health; and political will for scale-up. If successful, this stakeholder-based implementation model could be t...