# Estrogen reduces HPV transcription and oncogene expression to target disease

> **NIH NIH R03** · VIRGINIA COMMONWEALTH UNIVERSITY · 2021 · $147,488

## Abstract

Project Summary / Abstract
 Human papillomaviruses (HPVs) are the most common sexually transmitted infection
that affects nearly every sexually active individual at some point in their lives. A portion of these
infections can result in cancer, and worldwide, as many as 5% of cancers are caused by this
virus. There has been an increase in HPV-related head and neck cancer, and recently HPV has
bypassed smoking as the main cause of this disease. The HPV vaccine protects against future
infections but will not help anyone who already has HPV. As there are no treatments for this
virus, this is a much needed area of research. Promising targets for anti-HPV therapeutics
include viral replication and transcription. Here we present evidence that estrogen reduces HPV
transcription through interactions with the viral long control region (LCR). Novel regulatory
regions have also been discovered in the LCR that result in the loss of transcription. Reduced
LCR transcription via estrogen translates to a reduction in early viral genes, including the
oncogene E6. Lower levels of E6 allow for re-expression of the cellular tumor suppressor p53
and preliminary evidence suggests that this provides an HPV-specific loss in cell viability. The
proposal seeks to expand upon these results to determine if the estrogenic effects are cytostatic
or cytotoxic, and determine if these effects can be translated into an in vivo xenograft model.
Data generated from these studies will generate the necessary data for a future R01 application
to investigate the novel LCR regulatory regions, and possible sex related differences in the
response to estrogen treatment to elucidate why the incidence of HPV-associated HNSCC is
found at 3 fold higher levels in men than women, a currently understudied area. The ultimate
goals of this proposal and future studies generated from this data is to limit viral load, cure
infections, prevent downstream carcinogenesis, discover HPV-targeted cancer treatments, and
to translate these approaches to the clinic.

## Key facts

- **NIH application ID:** 10201571
- **Project number:** 5R03DE029548-02
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Molly L Bristol
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $147,488
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201571

## Citation

> US National Institutes of Health, RePORTER application 10201571, Estrogen reduces HPV transcription and oncogene expression to target disease (5R03DE029548-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10201571. Licensed CC0.

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