Cross Sectional Association of the Oral Microbiota and the Inflammasome with Oral HPV among HIV+ Adults

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PROJECT SUMMARY/ABSTRACT HPV-infection is the most common sexually transmitted disease (STI), and it accounts for 70% of oropharyngeal cancers. People living with HIV (PLWH) are disproportionately affected by HPV and are also at an increased risk of cancer development, even with suppressive antiretroviral therapy (ART), suggesting that ART may not fully recover oral HPV-specific immunity. Therefore, understanding other underlying factors that could facilitate the transmission and persistence of HPV in PLWH is crucial for the development of cancer prevention and surveillance strategies, and reduce the burden of HPV-associated malignancies in PLWH. The oral microbiota and inflammasome protein complex are essential factors for maintaining immune homeostasis factors, which are altered by HIV infection and have been observed in the pathogenesis of oropharyngeal cancer. Thus they represent novel targets for biomarker discovery and therapeutics. Our long-term goal is to investigate how these factors could contribute to immune dysregulation, and may affect the natural history of oral HPV infection in PLWH, in order to establish a set of early detection markers for HPV-related malignancies and personalized treatment interventions. We hypothesize that dysbiosis of the oral microbiome and inflammasome dysregulation can be risk factors for HPV-related complications and can contribute to the dampening the immune system promoting subsequent inflammation in PLWH. This cross-sectional study plans to recruit 200 virologically suppressed PLWH (men and women ≥21 and <49 years old) from a community-based organization, Puerto Rico (PR) CONCRA, that offers preventive and health services specialized in the treatment of the HIV and STI. PLWH who attends PR CONCRA constitute a unique high-risk group where the prevalence of both HIV and oral HPV infection is higher, allowing our team of experts in HIV, HPV, epidemiology, microbiology, oral health and bioinformatics to establish these relationships with high efficiency. The specific aims of this proposal are: (1) to characterize the oral microbiota in saliva and investigate its relationship with HPV status and HPV genotypes, and (2) to determine the association between the levels of inflammasome proteins (NLRP3, AIM2, and caspase- 1, IL-1β and cleaved IL-1β) and inflammation markers (IL-1β, IL-6, IL-8, TNF-α, IFN-γ) with oral HPV infection and HPV genotypes. After collection of saliva samples, participants will undergo oral health evaluations. Sociodemographic, behavioral, clinical characteristics, and risk factors will be collected through a questionnaire. Participants will be on stable, suppressive ART for at least 6 months to minimize inflammatory signals due to HIV active replication. We will characterize the oral microbiota by sequencing the 16S rDNA gene and HPV genotypes by PCR. Inflammasome proteins and inflammatory markers will be measured by Western Blot and multiplex ELISA respectively.