Background <p>Globally, Human Papillomavirus type 16 (HPV-16) is the predominant genotype associated with oropharyngeal cancers. However, little is known about the prevalence and type distribution of Oral Human Papillomavirus (OHPV) in people living with HIV (PLWHIV) in the East African region. The objective of this study was to document the prevalence and circulating genotypes of OHPV infection in a large cohort of PLWHIV attending an urban HIV clinic in Eastern Africa</p> Methods <p>This was a cross-sectional study among 1,715 participants of the Makerere University Joint AIDS Program clinic, located in Kampala, Uganda, in East Africa. A salivary sample was collected from which DNA was extracted and subjected to a Polymerase Chain Reaction (PCR) based typing. Data analysis was carried out among participants with complete data (<i>n</i> = 1,243) and relied on descriptive statistics (frequencies, percentages), bivariate testing and multivariate regression modeling, using a conventional <i>p</i> &lt; 0.05 statistical significance threshold.</p> Results <p>Participants had a mean age of 45 (SD = 10) years, and most (69%) were female. An exceptionally high OHPV prevalence of 67% was observed. The non-vaccine, high-risk genotype HPV-45 was the most prevalent type (16%), significantly exceeding the vaccine-targeted types HPV-type 18 (5%) and HPV-16 (2.3%). Most of the HPV-positive samples contained more than one HPV type.</p> Conclusion <p>This study highlights the high prevalence of OHPV among PLWHIV, with HPV-45 being the most frequently detected type, and smaller frequencies of vaccine-targeted HPV-16 and HPV-18. Our findings highlight the need for continued surveillance and typing of circulating OHPV strains, particularly among PLWHIV, to inform evidence-based preventive strategies.</p> Clinical trial number <p>Not applicable.</p>