Background: Human papillomavirus (HPV) infection is casually associated with oropharyngeal squamous cell carcinoma (OPSCC). International estimates suggest overall oral HPV prevalence is 7.5% (95% CI 9.7-8.4), with prevalence of oral HPV16/18 being 1.6% (95% CI 1.2-2.1). Prior Australian estimates suggest oral HPV prevalence is 2.3% (95% CI 0.6-3.9), with HPV16/18 being 1.3% (95% CI 0.0-2.6). Heck's disease is a benign condition caused by HPV types 13/32. The study aimed to estimate: (1) oral HPV prevalence among Indigenous Australians; (2) risk factors associated with high risk HPV types and; (3) risk factors associated with HPV types linked with Heck's disease. Methodas: Eligibility included identifying as Indigenous, residing in South Australia and being aged 18+ years. Saliva samples were collected, with microbial DNA for genotyping extracted. Socio-demographic parameters, health-related behaviours and sexual history data were collected. Analyses were stratified by sex, and by HPV types 13/32 (Heck's disease) and 16/18 (high risk for OPSCC). Findings: Data were obtained for 910 participants recruited between Feb 2018 and Jan 2019, age range 18-82 years, median age 37 years. Around one-third (35.3%, 95% CI 32.2-38.4) of saliva samples were positive for oral HPV (33.7% male, 36.1% female). The highest prevalence were HPV types 13/32 (22.7%; 19.0% male, 24.7% female) followed by HPV types 16/18 (3.3%; 2.9% male, 3.5% female). Associations with HPV types 13/32 included non-metropolitan residential status, low socioeconomic status, tonsillectomy, not having given oral sex, not having received oral sex or having sex with less than 4 people. Residing in a metropolitan location was associated with HPV types 16/18. Interpretation: Prevalence of oral HPV in a large sample of Indigenous Australians was high, with one-third testing positive. The most prevalent HPV types were those associated with Heck's disease. The prevalence of HPV types associated with OPSCC exceeded both Australian and international population-level estimates. Funding Statement: National Health and Medical Research Council APP1120215. Declaration of Interests: KC is co-PI of an investigator-initiated trial of primary HPV screening in Australia (‘Compass’) which is conducted and funded by the Victorian Cytology Service, a government-funded health promotion charity, which has received a funding contribution from Roche Molecular Systems, CA and Ventana Inc., USA, but neither KC nor her institution on her behalf have received funding from industry for this or any other project. All other authors declare no competing interests Ethical Approval Statement: Ethical approval was received from the University of Adelaide Human Research Ethics Committee and the Aboriginal Health Council of South Australia’s Human Research Ethics Committee. Participants signed informed consent forms.