Human papillomavirus-related oral lesions in people with HIV: A 20-year multinational cohort analysis

People with human immunodeficiency virus (PWH) are at increased risk of acquiring human papillomavirus (HPV) infection and subsequently developing HPV-related lesions. We aimed to determine the prevalence and strength of association between HPV-related oral lesions and HIV infection, using a large, real-world dataset.

This retrospective cohort used 20 years of de-identified electronic health records from TriNetX (109 organizations, 24 countries). Adults ≥18 years with HIV (ICD-10 B20, LOINC antibodies 7917-8/7918-6, RNA 25835-0) were compared age and sex matched people without HIV. We quantified prevalence and associations for HPV-related benign lesions (papilloma, verruca, epithelial hyperplasia, condyloma) and malignant oropharyngeal cancer (tonsil/base of tongue; ICD-O). Analyses excluded pre-study lesions, assessed oropharyngeal squamous cell carcinoma (OPSCC) after HIV diagnosis, and examined smoking effects within PWH.

In 253,847 PWH, condyloma (8.73 %) was most common, followed by verruca vulgaris (4.39 %), oral papilloma (2.63 %), epithelial hyperplasia (0.10 %), and HPV-OPSCC (0.26 %). All lesions were significantly more frequent than in people without HIV controls. OPSCC prevalence was 0.19 % in non-smokers, higher with smoking (0.26 %; odds ratio = 1.77). Elevated odds for OPSCC persisted in non-smokers, underscoring increased HPV-OPSCC disease risk in PWH regardless of tobacco exposure.

PWH face increased susceptibility to HPV-related oral lesions, particularly benign variants and OPSCC, with smoking further amplifying this risk. Despite the relatively low prevalence of OPSCC, there remains a critical need for targeted HIV care-including routine oral examinations, HPV vaccination, smoking cessation support, and advanced diagnostic approaches-to enable precise, evidence-based prevention strategies.