Objective Human papillomavirus (HPV) self-sampling (Self-HPV) may be used as a primary cervical cancer screening method in a low resource setting. Our aim was to evaluate whether an educational intervention would improve women's knowledge and confidence in the Self-HPV method. Method Women aged between 25 and 65 years old, eligible for cervical cancer screening, were randomly chosen to receive standard information (control group) or standard information followed by educational intervention (interventional group). Standard information included explanations about what the test detects (HPV), the link between HPV and cervical cancer and how to perform HPV self-sampling. The educational intervention consisted of a culturally tailored video about HPV, cervical cancer, Self-HPV and its relevancy as a screening test. All participants completed a questionnaire that assessed sociodemographic data, women's knowledge about cervical cancer and acceptability of Self-HPV. Results A total of 302 women were enrolled in 4 health care centers in Yaoundé and the surrounding countryside. 301 women (149 in the “control group” and 152 in the “intervention group”) completed the full process and were included into the analysis. Participants who received the educational intervention had a significantly higher knowledge about HPV and cervical cancer than the control group (p<0.05), but no significant difference on Self-HPV acceptability and confidence in the method was noticed between the two groups. Conclusion Educational intervention promotes an increase in knowledge about HPV and cervical cancer. Further investigation should be conducted to determine if this intervention can be sustained beyond the short term and influences screening behavior. Trials Registration International Standard Randomised Controlled Trial Number (ISRCTN) Register ISRCTN78123709
