Factors associated with acceptance of vaccination against human papillomavirus in eThekwini district of South Africa

South Africa launched a school-based human papillomavirus (HPV) vaccination programme in 2014 and has achieved a national coverage of more than 80%. However, there is subnational variation in coverage, with eThekwini District in the province of KwaZulu-Natal having the lowest coverage at 40%. Knowledge of the factors associated with vaccine acceptance in this district would inform tailored strategies to improve coverage, which could be extrapolated to similar settings. We conducted this cross-sectional study to assess the factors associated with HPV vaccine acceptance in eThekwini District. Methods: We used stratified random sampling to select caregivers of children aged 9–14 years in the district. We interviewed participants in April–May 2023 and employed bivariate and multivariate logistic regression models to assess the factors associated with HPV vaccine acceptance. Results: Of 793 individuals contacted, 713 (89.9%) participated. Most were women (86.1%) and had a mean age of 42.6 ± 11.6 years and secondary or lower education (83.8%). Most participants knew about the HPV vaccination programme (86.0%) and accepted HPV vaccination (93.5%). The latter includes 42.9% who had already vaccinated their daughters and 50.6% who were willing to allow their daughters to be vaccinated. A negligible proportion was either undecided (2.1%) or unwilling (4.4%) to accept HPV vaccination. Awareness of the programme (adjusted odds ratio [aOR] 5.22; 95% confidence interval [95%CI] 2.01–13.56), confidence in vaccine safety (aOR 19.69; 95%CI 5.86–66.15), and endorsement by religious leaders (aOR 5.06; 95%CI 1.56–16.45) were independent predictors of vaccine acceptance. Conclusions: Our findings highlight the critical role of the provision of information and education about the benefits and safety of HPV vaccination.