Abstract
Background/Objectives: Low HPV vaccine uptake persists in Saudi Arabia despite improving awareness. This study aimed to assess the level of awareness, knowledge, and uptake of the human papillomavirus (HPV) vaccine among female medical students in Saudi Arabia, and to identify key demographic, academic, and informational factors that predict vaccination behavior. It also sought to explore perceived barriers influencing vaccine acceptance within this population. Methods: A multi-center cross-sectional survey recruited 246 female medical students from five Saudi universities using convenience sampling. An anonymous, structured, and validated questionnaire assessed HPV/vaccine knowledge, attitudes, uptake, and perceived barriers. Data were analyzed using descriptive statistics, t-tests, ANOVA, correlation, and logistic regression. Results: Overall, 82.9% of participants had heard of HPV and 78.9% knew of the vaccine, but only 10.3% demonstrated high vaccine-specific knowledge. While 69.5% expressed willingness to be vaccinated, only 22.8% had received at least one dose. The most reported barriers were perceived lack of necessity (45.3%), abstinence from sexual activity (41.3%), and safety concerns (34.7%). Logistic regression indicated that higher academic year and higher vaccine-specific knowledge significantly predicted vaccine uptake (p < 0.001). Conclusions: Despite high general awareness, low vaccine-specific knowledge and cultural framing constrain HPV vaccine uptake among future prescribers. Universities should integrate cancer-prevention framing into curricula, strengthen female-to-female counseling, and provide on-campus vaccination opportunities. Addressing knowledge gaps and sociocultural barriers is critical to improving HPV vaccine coverage in Saudi Arabia.