Characterizing Oral Microbiome and Periodontal Disease in Oral HPV-Positive (COMP-HPV) individuals with HIV: an observational longitudinal study protocol.

backgroundHuman papillomavirus (HPV) is a major cause of oropharyngeal and other cancers, occurs more frequently among people with HIV (PWH). Despite antiretroviral therapy, HPV-related cancer incidence remains elevated in this group. Oral dysbiosis in PWH may impair mucosal immunity, promoting HPV persistence and inflammation. Periodontal disease, frequently observed in PWH, further contributes to microbial imbalance and immune dysregulation, increasing susceptibility to oral HPV infection. This study investigates the relationship among oral microbiome composition, periodontal disease and oral HPV infection behavior in PWH, considering immunologic and social determinants of health.

methodsThe characterizing oral microbiome and periodontal disease in oral HPV-positive individuals (COMP-HPV), an observational longitudinal study will enroll 500 PWH and follow them up for two years. Oral rinse for HPV testing and periodontal assessment will be collected every six months; saliva for inflammatory markers, oral rinse for microbiome and oral cytobrush for immunological profiling will be collected annually. Immune profiling will include high-dimensional flow cytometry and 10X RNA-sequencing to characterize innate and adaptive immune subsets, with emphasis on HLA-DR–positive populations, enabling evaluation of oral immune modulation during HPV infection. The study has four specific aims such as to examine associations between oral microbiome composition (16S and metagenomics) and oral HPV infection, including prevalence, incidence, persistence, and clearance; to assess the impact of periodontal disease on oral HPV infection and investigate whether the oral microbiome mediates this relationship; to determine how oral microbiome composition influences immunological responses in HPV-positive PWH and to evaluate the role of social determinants on oral microbiome composition and HPV infection. Data from this longitudinal study will be used to understand the natural history of oral HPV infection, the interplay with periodontal disease, microbial alterations, and immunological changes, providing evidence to guide interventions for reducing HPV-associated disease in PWH. TRIAL REGISTRATION NUMBER: Not applicable. DISCUSSION: The COMP-HPV study aims to contribute to the body of research designed to investigate mechanisms underlying oral HPV infection among PWH to improve immune responses to reduce HPV infection and relevant carcinoma.