Detection and natural history of HPV infection of oral cavity and tonsils – a systematic literature review

Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) is increasing, with HPV16 being the most prevalent type. Persistent oral HPV infections play a causal role in the pathogenesis of these cancers. The objective of this systematic review was to summarize current data on oral HPV prevalence in the general population and in people living with HIV (PLWH), possible effects of prophylactic vaccination and optimal sampling methods for the detection of HPV in the oral cavity. We searched Medline and Livivo for publications on oral HPV prevalence in cohorts > 1000 individuals (> 100 individuals for cohorts of PLWH) released between January 2012 and October 2024. In total, 51 original studies and meta-analyses were included in this review. Overall prevalence of oral HPV infection in general population/healthy individuals was between 0.67 and 11.89% (mean 5%) and was higher in males than in females. Prevalence of oral high-risk HPV ranged between 0.5 - 4.7%. The most prevalent HPV-type detected was HPV16. Risk factors for oral HPV infection comprised older age, male sex, the number of lifetime (oral) sex partners, smoking, drug abuse, oral health and concurrent genital HPV infection. Compared to the general population, higher oral HPV prevalence rates were detected in PLWH (2 - 40%, mean 20%). HIV infection has been established as an independent risk factor for oral HPV infection irrespective of gender or sexual orientation. Concerning prophylactic HPV vaccination of adolescents and young adults there is evidence from clinical and epidemiological studies showing prevention of oral HPV infection in vaccinated individuals. Oral HPV-DNA can be found in 1-12% of the general population, more frequently in men than in women. PLWH have an increased oral HPV prevalence compared to the general population. Since prophylactic HPV vaccination is associated with a significant reduction in vaccine-type oral HPV prevalence, high vaccination rates in children and adolescents are important to counteract the rising incidence rates of HPV-associated OPC in the future. Comprehensive research on oral HPV clearance and persistence and on optimal sampling methods is still pending.