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Introduction: Harris County, Texas is the 3rd largest county in the United States, and home to a large ratio of racial/ethnic minorities and immigrants. It has one of the highest rates of cervical cancer, where nearly all cases are caused by human papillomavirus (HPV), with the incidence rate highest among African Americans and Hispanics/Latinos. A wealth of medical resources exist, yet HPV-related cancers have failed to improve over the past 10 years. Youth are particularly at risk for HPV infection and are more likely to not receive the HPV vaccine. The aim of this research was to better understand the factors influencing HPV vaccination among youth in Harris County and to develop an evidence-based approach to improve vaccine uptake. Methods: A socio-ecological framework was used to identify key stakeholders. Data was collected using a mixed methods approach between October 2014 and October 2015 in Harris County, Texas. One focus group and 31 focused interviews were conducted with parents of 5-18 year old children. Seven key informant interviews were conducted with school nurses; a political leader; and health professionals from adolescent health clinics, pediatric hospitals, health centers, community-based organizations (CBOs), and medical institutions. Three community advisory board (CAB) meetings were held with school nurses and board members; physicians; and health professionals from health departments, CBOs, and educational and advocacy organizations. Results: Parents Most parents lacked knowledge of HPV and the vaccine. Many felt the best way to receive education was from their providers. Others expressed interest in receiving education from schools, the media, seminars, and community involvement. Spanish-speaking parents emphasized the need for more linguistically appropriate literature. Some parents voiced discomfort with vaccinating 9-12 year olds, mainly due to safety concerns and vaccine efficacy. Physicians' recommendations were an influential factor in some parents' decision making regarding vaccination. Other key stakeholders Lack of education about HPV infection and the vaccine was cited as a major barrier to vaccination. CAB participants often felt misinformed by their providers, and stated some physicians lack time to hold discussions and fail to provide confident recommendations. Perceived negative side effects; cultural and religious beliefs; lack of reminders for the 2nd and 3rd doses; and labeling the vaccine as a cervical cancer and sexual vaccine were noted as other barriers. Health clinics felt some providers' recommendation approaches were a barrier. Mistrust of the healthcare system was reported as common in Hispanic/Latino communities, and lack of engagement in preventable activities was described as common in African American and immigrant communities. It was stressed that education targeting parents, use of the opt-out approach for provider recommendations, and promoting the vaccine as a cancer-prevention vaccine are essential to increasing HPV vaccine uptake. Conclusions: Comprehensive educational interventions at the provider-, school-, and community-level are needed to ensure that physicians, parents, patients, and educators receive accurate information. Provider trainings can equip physicians with the accurate knowledge needed to make confident recommendations; emphasize use of the opt-out approach for recommendations; and provide them with multilingual educational materials to share with parents and patients. Collaborative efforts with school board members and parent organizations/associations can encourage inclusion of HPV in the curriculum, and foster discussions among parents and educators. Community-based interventions should focus on innovative, culturally-appropriate ways to disseminate education messages in medically, underserved communities. Citation Format: Aba Coleman, Marva Mallory, Jane Montealegre, Peggy Smith, Ruth Buzi, Michael Scheurer, Maria Daheri, Maria Jibaja-Weiss, Matthew Anderson. Understanding the influential factors to human papillomavirus vaccination among youth in Harris County, Texas: A qualitative study. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr A46.