# The role of bacterial vaginosis-associated bacteria in papillomavirus persistence and cancers

> **NIH NIH R21** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2022 · $186,993

## Abstract

ABSTRACT
HPV is one of the most common sexually transmitted diseases worldwide and is the caustic factor for about
5% of all human cancers. Most cases of cervical cancer (>96%) and oropharyngeal cancer (70%) are
associated with HPV infections. Although current HPV vaccines have successfully decreased the prevalence of
HPV types covered in the vaccinated groups, the prevalence of HPV types not covered by vaccines is still high.
Currently, no curative treatments are available to millions of individuals with preexisting HPV infections. Our
proposed study aims to address the knowledge gap raised in PAR-20-061 in understanding “the role of co-
infection in cancer etiology and progression”. Emerging experimental and observational studies have
demonstrated that vaginal microbiota may play a critical role in HPV-associated disease progression to cancer.
We propose to test several novel hypotheses including vaginal bacteria and their metabolites as potential
drivers or suppressors of immune responses linked with progression/regression of cervical cancers in humans.
In healthy women, the vaginal microbial environment is dominated by lactobacillus species, polymicrobial
microbiome profiles (CST-I). Several non-lactobacillus species, including polymicrobial microbiome profiles
(CST-III and -IV), are associated with increased HPV infection/persistence and neoplasia formation.
Interestingly, individuals with a relatively small lactobacillus (CST-I) community in the vagina are commonly
colonized by non-lactobacillus bacteria (CST-III and -IV), which is characteristic of BV. Our preliminary in vivo
studies have demonstrated that non-lactobacillus bacteria Gardnerella vaginalis and Mobiluncus mulieris
(CST-IV) changed inflammatory pathways, thereby suggesting G. vaginalis and M. mulieris may promote
papillomavirus persistence in the genital tract. We hypothesize that papillomavirus co-infection with BV-
associated bacteria promotes viral persistence and genital mucosal dysplasia. To test our hypothesis, we will
use our novel mouse papillomavirus and vaginal bacterial infection models to 1) determine the changes of
endogenous vaginal microbiota that are associated with high vaginal dysplasia in both immunocompromised
and immunocompetent mice (Aim 1); 2) determine the interaction between BV-associated bacteria and
metabolites and papillomavirus associated tumor progression (Aim 2). This is the first such study in both the
microbiome and papillomavirus fields. Our findings will shed light on an understudied yet significant problem in
cervical cancer development that is relevant to humans.

## Key facts

- **NIH application ID:** 10432590
- **Project number:** 1R21CA271069-01
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Jiafen Hu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $186,993
- **Award type:** 1
- **Project period:** 2022-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10432590

## Citation

> US National Institutes of Health, RePORTER application 10432590, The role of bacterial vaginosis-associated bacteria in papillomavirus persistence and cancers (1R21CA271069-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10432590. Licensed CC0.

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