# Antibody bound bacteria during HPV infection and cervical dysplasia

> **NIH NIH R21** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $184,528

## Abstract

PROJECT SUMMARY
High-risk human papillomavirus (HR-HPV) is a known cause of >95% of cervical cancer and cervical
intraepithelial neoplasia (CIN). Prophylactic vaccines are available against the most carcinogenic types and are
highly effective, but the number of people receiving the vaccine is low, and vaccines are ineffective in women
who have already developed CIN. Initial infection of HPV results in low-grade CIN (CIN1) and is mostly cleared
by the immune system. However, failure of the immune system to clear HPV can lead to chronic infection and
risk of high-grade CIN (CIN2 or CIN3) or invasive cervical cancer. There is emerging evidence that the vaginal
microbiome plays an important role in this process however the mechanisms linking vaginal bacteria with host
responses to HPV infection and cervical neoplasia progression are underexplored.
Antibody binding to microbes can alter the structure and function of the microbiome, however this has not been
comprehensively characterized in the female reproductive tract. Our overall hypothesis is that the proportion,
abundance and/or functional profiles of antibody bound and unbound vaginal bacteria will differ between women
with and without HPV infection, as well as those with normal cervical pathology, low-grade cervical lesions, and
high-grade cervical lesions. Our overall goal is to define the associations between the proportion and
abundance of antibody bound and unbound bacteria and their functions in these comparison groups. In this
proposal we will utilize vaginal samples already collected from a comprehensive observational cohort (THRIVE
HPV) that is specifically recruiting women with an abnormal pap smear test and following them longitudinally for
2-3 years to determine HPV status and regression or progression of cervical dysplasia. We will sort bacterial
cells from vaginal swab samples at baseline enrollment into antibody bound and unbound fractions, then perform
metagenomics to determine the abundance, species/genera, and functions of bacteria that are associated with
antibody bound or unbound bacteria in each comparison group. A unique feature of this proposal is having
access to longitudinal samples from a diverse (>50% African American) cohort for this and future studies to
determine antibody bound and unbound bacterial stability over time, with comprehensive medical and
pathological information.
To the best of our knowledge, our work will be the first to define antibody bound and unbound vaginal
bacterial populations at the species/strain level in women with or without HPV infection or different
cervical pathologies. We anticipate this study will reveal antibody bound bacterial populations that are
associated with a healthy or diseased microenvironment that can be identified as high-risk profiles needing to
be monitored for treatment or targeted for novel immunological therapeutics.

## Key facts

- **NIH application ID:** 10867912
- **Project number:** 1R21CA289927-01
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Stephanie N. Langel
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $184,528
- **Award type:** 1
- **Project period:** 2024-08-08 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10867912

## Citation

> US National Institutes of Health, RePORTER application 10867912, Antibody bound bacteria during HPV infection and cervical dysplasia (1R21CA289927-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10867912. Licensed CC0.

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