Short Chain Fatty Acids: Route for Facilitation of Oral HPV via Inflammasome Dysregulation in People Living with HIV

PROJECT SUMMARY/ABSTRACT The oral microbiota and inflammasome protein complex are essential factors for maintaining immune homeostasis, which are altered by an HIV infection and have been observed in the pathogenesis of oropharyngeal cancer. Short chain fatty acids (SCFA) in the oral cavity, such as butyrate, exacerbates

periodontal tissue damage, which can act as an oncometabolite and lead to the development of HPV-related oral and pharyngeal carcinogenesis. Furthermore, butyrate has been found to regulate the transcription of immune-related genes. Particularly, it upregulates local inflammation while downregulates the expression of

interferon-related genes and upregulates inflammasome-related markers, necessary for the innate immune response to a viral infection. Therefore, butyrate could play an essential role on immune dysfunction by dysregulating the inflammasome and facilitating oral HPV infection, increasing cancer risk in people living with

HIV (PLWH). Therefore, our overall objective is to quantify oral SCFA in PLWH with an without HPV infection with the central hypothesis that PLWH with oral HPV infection will have higher levels of butyrate, which will be associated with periodontal disease, dysbiosis of the oral microbiome, more inflammation and more

inflammasome dysregulation. This supplement plans to use samples from 50 virologically suppressed PLWH (25 HPV+ and 25 HPV-), aged ≥21 and