# Enlisting HPV integration events to illuminate drivers and target treatment in invasive cervical cancer

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2024 · $441,173

## Abstract

PROJECT SUMMARY
Invasive cervical cancer (ICC) kills nearly 311,000 women each year worldwide with an estimated 50%
increase in deaths by 2040. In the U.S., ICC ranks third for average years of life lost and
disproportionately affects minority groups and women of low socioeconomic status. Women with
advanced or recurrent ICC soon develop resistance to current chemotherapy options, and about 90%
die within 2 years. Our intent is to define clinically relevant and targetable ICC genes and pathways to
improve patients’ treatments and outcomes. Our central hypothesis is that HPV integration events—and
the changes they exert on the host genome and epigenome—confer a selective advantage to disease
progression and provide opportunities to pinpoint genes and pathways relevant to treating ICC. Using
The Cancer Genome Atlas (TCGA) ICC cohort (CESC), we developed a pipeline to identify integration
detected genes (IDGs) altered by HPV integration in some ICCs and by genomic and/or epigenomic
modifications in other ICCs. Elements of our pipeline focus on proximity to the integration site, clonal
representation of the integration event, patient- and disease-specific gene expression, association with
ICC survival, and frequency of alteration in ICC. For this proposal, we will expand our discovery pipeline
to a newly completed multi-omics ICC cohort, the HTMCP (HIV+ Tumor Molecular Characterization
Project), incorporating new technology and testing the functional contribution of IDGs to ICC and
chemoresponse. This in-depth characterization of a plethora of IDGs will help us identify novel
targets/pathways which is a critical step towards better therapy for women with ICC. To this end, we will
pursue the following Specific Aims: Identify and filter IDGs from HPV integration sites in HTMCP
samples using our established pipeline, long-read DNA and cDNA sequencing, and other genomic
studies (Aim 1), determine the functional contribution of IDGs to ICC and their therapeutic targeting
potential using siRNA-mediated KD and/or CRISPR-based gene editing in cervical cancer cell lines and
orthotopic xenograft models, (Aim 2), and determine the clinical relevance and biomarker potential of
IDGs (Aim 3).

## Key facts

- **NIH application ID:** 10861758
- **Project number:** 5R01CA262198-03
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Janet S. Rader
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $441,173
- **Award type:** 5
- **Project period:** 2022-07-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10861758

## Citation

> US National Institutes of Health, RePORTER application 10861758, Enlisting HPV integration events to illuminate drivers and target treatment in invasive cervical cancer (5R01CA262198-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10861758. Licensed CC0.

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