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

> **NIH NIH R21** · COMPREHENSIVE CANCER CENTER/ UNIV/PR · 2022 · $7,524

## Abstract

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<49 years old from the parent study. The specific aims of this proposal
is (i) to quantify the levels of microbial SCFA in saliva of PLWH and assess their relationship with infection and
HPV genotypes (high-risk vs. low-risk) and (ii) To determine the association between the levels of SCFA with
periodontal disease, oral microbiome dysbiosis, inflammasome dysregulation and levels of inflammation
markers. SCFA will be measured by liquid chromatography followed by mass spectrometry. We will leverage
HPV genotyping (PCR), oral microbiome data (16s rDNA profiling), inflammasome proteins levels (western blot)
and inflammatory markers (multiplex ELISA) from the parent study. This award will directly support Mr. Yabdiel
Ramos-Valerio in achieving expertise in microbiome research and data analysis, including large-scale
metagenomics data and statistical analysis and epidemiological research focused on HIV, HPV, and cancer. He
will also take courses and focused mentorship on expanding his knowledge and experience in designing,
implementing, and completing a clinical/translational research study. Finally, he will further develop the academic
skills that will ensure his successful, independent research career, including responsible conduct of research,
scientific writing, oral communication skills, grantsmanship, and collaborative interdisciplinary research. This
supplement will provide him with resources toward achieving his goal of being accepted in MD/PhD programs
and eventually become an independent research physician specializing in pathogen-driven cancers.

## Key facts

- **NIH application ID:** 10532974
- **Project number:** 3R21CA264606-01S1
- **Recipient organization:** COMPREHENSIVE CANCER CENTER/ UNIV/PR
- **Principal Investigator:** Josue Perez-Santiago
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $7,524
- **Award type:** 3
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10532974

## Citation

> US National Institutes of Health, RePORTER application 10532974, Short Chain Fatty Acids: Route for Facilitation of Oral HPV via Inflammasome Dysregulation in People Living with HIV (3R21CA264606-01S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10532974. Licensed CC0.

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