Background: Human Papillomavirus (HPV) infection is the most prevalent viral infection affecting the reproductive tract, and it is a leading cause of cervical cancer—the fourth most common cancer among women globally. Vaccination against HPV serves as an effective preventive measure, particularly among young adults, who are at increased risk.

Objective: This study examined factors influencing HPV vaccine uptake among female undergraduate students at the University of Calabar, Nigeria

Methods: A non-experimental quantitative approach utilizing a descriptive cross-sectional survey design was adopted. The study included 213 female undergraduate students selected through a multi-staged sampling technique. Data were collected using a structured questionnaire administered face-to-face, ensuring ethical considerations such as informed consent and confidentiality. Data analysis was performed with SPSS version 23, and results were presented using percentages and Chi-Square test to explore associations.

Results: Findings revealed a low rate of HPV vaccine uptake among participants, with only 2.3% of the 213 students reporting they had received the vaccine. Lack of awareness emerged as a major barrier to uptake, with 58.2% of students indicating they had not heard of the HPV vaccine prior to the study. Additionally, fears of vaccine side effects (mean=3.17), religious beliefs (mean=2.95), and misconceptions associating vaccination with promiscuity (mean=1.73) contributed to hesitancy. Notably, students who were married (13.1% of participants) or had higher monthly incomes (10.8% earning above ₦100,000) showed higher uptake rates. Furthermore, students with higher knowledge levels about HPV demonstrated significantly higher rates of vaccine acceptance, as indicated by the significant association between knowledge levels and vaccine uptake (p=0.003). Conclusion: This study highlights the urgent need for tailored educational interventions to improve HPV vaccine awareness and address misconceptions among female undergraduates.