Background Human papillomavirus (HPV) infection is a common sexually transmitted disease, characterised by persistent infection with high-risk strains leading to malignant conditions such as cervical cancer. The HPV vaccine is a well-known primary preventive measure for HPV infections. Previous studies have shown that medical doctors’ vaccine recommendation is one of the key strategies in improving HPV vaccine uptake. In 2019, Zambia rolled out the free national HPV vaccination program targeting 14-year-old girls. However, the annual coverage for HPV vaccination is variable, with rates as low as 33% for 2021. Materials and Methods We conducted a cross-sectional study between September and December 2020 at the University Teaching Hospitals in Lusaka, Zambia. We used analysis of variance to assess the mean differences in the overall scores for knowledge, attitude and practices towards the HPV vaccine. In addition, we used structural equation modelling (SEM) to test the traditional education theory as medical doctors’ HPV vaccine knowledge, attitude, and practices cover several facets, and SEM can model latent variables. Results We enrolled 121 medical doctors, of whom 67 (44.6%) were male. The majority, 76 (62.8%), were registrars and 79 (65.3%) had more than ten years of clinical experience. The overall mean knowledge, attitude, and practice score of the HPV vaccine mean (SD) were 70.2 (15.1), 72.1 (18.5) and 77.1 (28.9), respectively. More than half of the medical doctors would advise anyone eligible to take the HPV vaccine 66 (54.6%). There was a positive correlation between attitude and practice towards the HPV vaccine (β = .03, P = .017). Conversely, there was no evidence of a correlation between overall HPV knowledge and attitude (β = .01, P = .670) and rank of the medical doctors (β = −7.87, P = .355). Conclusion Knowledge was high with good attitudes and practices among medical doctors, which are vital in vaccine recommendation and subsequent uptake.

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