# Investigating whether chlamydia trachomatis can increase the infectivity of HPV during genital tract infections

> **NIH NIH R21** · MARIAN UNIVERSITY · 2024 · $168,753

## Abstract

Project Summary
Although the estimated lifetime risk of human papillomavirus (HPV) infection can be as high as 75% in unvaccinated
women, the actual risk of developing cervical cancer is only ~0.68%. This indicates that exposure to HPV alone is
insufficient for the development of cervical cancer and that HPV infections likely require the presence of a biological or
cellular induced “co-factor” to help trigger oncogenesis. As the most common bacterial sexually transmitted pathogen and
because it too is a significant threat to the reproductive health of women, Chlamydia trachomatis (Ct) infections are
increasingly being linked to gynecological cancer development as epidemiological reports indicate that co-infections with
Ct and HPV are relatively common. Meta-analyses of the epidemiological data and the early investigations into the putative
role of Ct in gynecological cancers have implicated the cellular immune response to chlamydial infection as a potential co-
factor that can enhance the host’s susceptibility to HPV-induced cervical cancers. We and others have shown that the
immune response to Chlamydia infection results in genital tract pathology and our most recent report shows that TLR3
deficiency in HUMAN oviduct epithelial (hOE) cells alters the immune response to Ct infection, resulting in increased
chlamydial replication. We also recently reported that Chlamydia infection induces the syntheses of cellular factors that
disrupt cell-cell junctions in genital tract tissue and that TLR3 deficiency leads to increased monolayer permeability during
Chlamydia infection. Our data support other studies showing that Chlamydia infection can disrupt the protective epithelial
barrier function, and we also presented evidence that TLR3 plays a role in maintaining the integrity of the epithelial barrier
during genital tract Chlamydia infection. Therefore, we hypothesize that Chlamydia infection disrupts epithelial barrier
function (which is in part modulated by TLR3), and the barrier disruption will allow better access to the underlying basal
cell layers and thereby can increase the infectivity of HPV. In this proposal, we will test our hypothesis that Ct can serve
as a co-factor in HPV-infection-induced cervical cancer by: (1) examining whether Chlamydia infection or secreted
products of Chlamydia infection can enhance the attachment and entry of HPV into their target cells, (2) determining if
TLR3 signaling modulates the impact that Ct has on increasing HPV infectivity, and (3) ascertaining if genital tract
Chlamydia infection will make mice more susceptible to subsequent papillomavirus infections. Confirmation of our
hypothesis would reveal novel insight into Ct-HPV coinfection, the role of TLR3 in altering outcomes of coinfection, and
implicate TLR3 as a potential target for therapeutic interventions to prevent Ct-triggered oncogenesis in HPV-infected
patients.

## Key facts

- **NIH application ID:** 10807056
- **Project number:** 5R21AI175847-02
- **Recipient organization:** MARIAN UNIVERSITY
- **Principal Investigator:** WILBERT A DERBIGNY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $168,753
- **Award type:** 5
- **Project period:** 2023-03-10 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10807056

## Citation

> US National Institutes of Health, RePORTER application 10807056, Investigating whether chlamydia trachomatis can increase the infectivity of HPV during genital tract infections (5R21AI175847-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10807056. Licensed CC0.

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