# Multi-Omics Predictors of Oral HPV Outcomes among PLWH

> **NIH NIH P20** · UNIVERSITY OF PUERTO RICO MED SCIENCES · 2024 · $278,797

## Abstract

PROJECT SUMMARY/ABSTRACT
Advances in antiretroviral therapy (ART) have not reduced the disproportional incidence and prevalence of oral
human papilloma virus (HPV) and oropharyngeal cancers in people living with HIV (PLWH), suggesting ART
alone may not fully restore mucosal immunity. This may be because HIV alters the oral microbiome, affecting
mucosal immunity, and biological aging, such as changes in DNA methylation and immune senescence, can
worsen HIV-associated immunosuppression. Reshaping the microbiome or reprogramming DNA methylation
patterns may be a safe way to identify, prevent, or treat HPV persistence; however, understanding how these
factors interact to promote cancer is a crucial gap in our existing knowledge. Our objective is to investigate
these two biological processes (oral microbiome, biological aging), combined with socioeconomic and behavioral
factors (sexual practices, lifestyle factors) to determine the impact of the natural history of HPV infection in
PLWH, and to construct a machine learning classifier using these factors that can predict HPV infection and
persistence. Our overarching hypothesis is that dysbiosis of the oral microbiome and older methylation aging
are risk factors for HPV-related complications and can dampen the mucosal immune response in PLWH.
Therefore, this proposed longitudinal study plans to collect saliva at two time points (baseline and after six
months) from 150 virologically suppressed PLWH (men and women, ≥21 years old) from Puerto Rico CoNCRA,
a community-based organization specialized in the prevention and treatment of HIV. PLWH who attend 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, cancer biology, oral health and bioinformatics to
establish these relationships with high efficiency. The specific aims of this proposal are: (1) to determine how
HPV incident infection and persistence affects the oral microbiome and oxidative stress in saliva in PLWH, (ii) to
characterize the oral methylome of PLWH with and without HPV and assess the impact of methylation aging in
the natural history of HPV infection, and (iii) to construct a diagnostic and prognostic classiﬁer based on biological
data (microbiome and methylation) and socio-behavioral characteristics capable of discriminating HPV infection
and persistence among PLWH. We will characterize the oral microbiota by 16S rDNA sequencing, HPV
genotypes by PCR, DNA methylation by Illumina Infinium Methylation BeadChip arrays and oxidative stress by
immuno spectrophotometry assays. Additionally, remaining saliva and voluntary blood collection will be used to
create a biorepository for future research. This study leverages resources from the UPRCCC and CePCHE
including (i) the UPRCCC Biobank for the biospecimen storage, (ii) the Biostatistics and Bioinformatics Core for
assistance in the analyses and storage of the data generated, and ...

## Key facts

- **NIH application ID:** 10931335
- **Project number:** 5P20GM148324-02
- **Recipient organization:** UNIVERSITY OF PUERTO RICO MED SCIENCES
- **Principal Investigator:** Josue Perez-Santiago
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $278,797
- **Award type:** 5
- **Project period:** 2023-09-19 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10931335

## Citation

> US National Institutes of Health, RePORTER application 10931335, Multi-Omics Predictors of Oral HPV Outcomes among PLWH (5P20GM148324-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10931335. Licensed CC0.

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