# The Microbiome as a risk factor for hr-HPV persistence and Cervical Cancer

> **NIH NIH U54** · UNIVERSITY OF PUERTO RICO MED SCIENCES · 2022 · $319,086

## Abstract

PROJECT SUMMARY
Cervical cancer (CC) is the fourth most common female malignancy worldwide. Mortality rates are three times
higher in Latin America and the Caribbean than in the United States, and Puerto Rico (PR) has the highest
age-adjusted incidence for cervical cancer in the US despite of vaccination. Persistent infection with high-risk
human papilloma virus (hr-HPV) types is a necessary, but not sufficient to cause cervical cancer. Other yet
unknown cofactors are required to promote hr-HPH persistence and progression to cancer, however these
pathways are not completely understood. Besides HPV infections, the key factors that promote cancer
progression likely reside in the cervical environment, notably its local microbiome. Preliminary evidence
suggests that increased bacterial diversity and reduction in Lactobacillus are associated with High grade
squamous intraepithelial lesion (HSIL), however, except for preliminary data from our group that studied
cervical yeast, we have not yet understood the importance of the fungal communities and other combined
metabolic and host factors on disease progression. Here we propose to comprehensively study virus-
microbiota-host interactions, using state of the art sequencing technologies and novel bioinformatic algorithms
to address a malignancy, that is characterized by health disparities in the US and globally. Our overarching
goal is to identify microbial inter-species interactions and host factors that control hr-HPV persistence
and cervical disease. We will leverage samples and data already collected from over 300 participants in a
cross-sectional pilot study cohort, and to additionally select 200 participants to follow up longitudinally.
In Aim 1, we will quantify the cervicovaginal bacterial and fungal community composition and metabolome
cross-sectionally, differentiating women with or without cervical dysplasia and presence or absence of high risk
(hr) HPV. In Aim 2 we will identify bacterial and fungal strains, functional gene pathways and metabolites that
over a longitudinal timeseries distinguish women without cervical disease (NILM - HPV negative and low-risk),
from high-risk HPV infected women who progress to high grade dysplasia. Having shotgun metagenomics data
from selected patients longitudinally is unique to be able to understand gene and functional changes of key
taxa to inform on their role in progression or regression. We hypothesize that there will be genomic bacterial
strains that differentiate women without lesions and with cervical disease and that multiple levels of omics data,
including the microbiome, the metabolome and the cytokine profiles may have higher predictive value than
HPV risk alone. This work will develop a strong platform for a long standing and central question regarding
cervical disease in Hispanics and will lay the foundation for elucidating the mechanisms by which
microbiomes affect HPV persistence and dysplasia.

## Key facts

- **NIH application ID:** 10556249
- **Project number:** 2U54MD007600-36
- **Recipient organization:** UNIVERSITY OF PUERTO RICO MED SCIENCES
- **Principal Investigator:** FILIPA GODOY-VITORINO
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $319,086
- **Award type:** 2
- **Project period:** 1997-09-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10556249

## Citation

> US National Institutes of Health, RePORTER application 10556249, The Microbiome as a risk factor for hr-HPV persistence and Cervical Cancer (2U54MD007600-36). Retrieved via AI Analytics 2026-06-03 from https://api.ai-analytics.org/grant/nih/10556249. Licensed CC0.

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