BackgroundHuman papillomavirus (HPV) infection is strongly associated with cervical cancer with almost all cases being associated with the infection. Cervical cancer is the leading cause of cancer death among women in Zambia and the fourth leading cause of cancer death in women worldwide. However, there is limited data on the burden and associated factors of HPV in sub-Saharan Africa. This study aimed to determine the prevalence and correlates of HPV infection in the Southern province of Zambia.MethodsThis was a cross-sectional study conducted at Livingstone University Teaching Hospital (LUTH) among 4,612 women from different districts of the southern province being screened for HPV infection between September 2021 and August 2022. Demographic and clinical data were collected from an existing laboratory programmatic database. Multivariable logistic regression was used to estimate the factors associated with HPV infection.ResultsThe study participants had a median age of 39 years [interquartile range (IQR) 30, 47]. The prevalence of HPV infection was 35.56% (95%CI). At multivariable analysis, the factors associated with a positive HPV result were younger age (adjusted odds ratio (AOR) 0.98; 95% confidence interval (CI) 0.98-0.99; p. value 0.001), having provider collected sample (AOR 2.15; 95%CI 1.66 -2.79; p. value <0.001) and living with HIV (AOR 1.77; 95%CI 1.22 – 2.55; p. value <0.002).ConclusionThe prevalence of HPV in women in the southern province of Zambia is high, and likely influenced by age and HIV status. Additionally, the outcome of the HPV test is affected by the sample collection method. Therefore, there is a necessity to enhance HPV and cervical cancer screening, especially among people with HIV.