Abstract Background: Human Papillomavirus (HPV)-associated cancers disproportionately impact Latinos. While data for English-speaking (ES) and Spanish-speaking (SS) Latinos is usually aggregated, differences in acculturation, sociodemographic characteristics, and health behaviors make it important to understand the factors impacting HPV vaccination among these groups separately. This understanding is crucial to improving HPV vaccination disparities as COVID-19 vaccinations have exacerbated issues of vaccine hesitancy and medical mistrust. Methods: Self-administered online surveys examining HPV vaccine hesitancy in an urban, diverse community with low HPV vaccine uptake were completed by parents of adolescents (N=357) in English or Spanish. Bivariate logistic regression analyses were conducted to understand if medical mistrust, vaccine hesitancy, HPV knowledge, healthcare utilization and sociodemographic factors impact adolescent HPV vaccine uptake among ES and SS parents of Latino adolescents ages 12-17. Factors significant at p<.01 in the bivariate analyses were included in multivariable logistic regression models for each group. Results: 136 parents of adolescents aged 12-17 identified as Latino; 56% completed the survey in English and 44% in Spanish. Bivariate analyses found significant associations between decreased HPV vaccine uptake and male parent/caregiver sex, higher HPV vaccine hesitancy, higher HPV knowledge, male adolescent sex, not receiving the flu vaccine and not receiving a provider recommendation to vaccinate against HPV among ES parents. In SS parents, parents aged 41-50 (compared to <40) and higher medical mistrust were associated with higher HPV vaccination; while male adolescent gender, not receiving TDAP immunization, and not receiving a provider recommendation to vaccinate against HPV were associated with lower HPV vaccine uptake. Multivariable regression models found that adolescents of ES parents were less likely to have initiated the HPV vaccine series if the parent/caregiver was male (OR=0.07, 95% CI:0.03,1.28), had higher HPV knowledge (OR=0.53, 95% CI:0.29,0.96), and did not receive a provider recommendation to vaccinate against HPV (OR=0.12, 95% CI:0.003,0.55). SS parents with higher medical mistrust (OR=7.27, 95% CI:1.14,46.41) and those aged 41-50 compared to parents younger than 40 (OR=18.19, 95% CI:0.28,407.78) were more likely to have adolescents who initiated the HPV vaccine series, while those without a provider recommendation to vaccinate had lower odds of HPV vaccine uptake (OR=0.004, 95% CI:<0.01,0.11). Discussion: Aligned with the literature, provider recommendation to vaccinate against HPV significantly impacted vaccination behavior among ES and SS parents. Interventions should focus on improving provider recommendations and communications with Latino parents of adolescents. More research should explore the surprising associations between higher medical mistrust and higher odds of HPV vaccination among SS parents, and more HPV knowledge and lower odds of HPV vaccination among ES parents. Citation Format: Bibiana Martinez, Lourdes Baezconde-Garbanati, Jennifer Tsui. Factors impacting HPV vaccine initiation among English and Spanish speaking parents of Latino adolescents [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A127.