# Defining HPV integration sites of unknown significance in invasive cervical cancer

> **NIH NIH R21** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $401,115

## Abstract

PROJECT SUMMARY/ABSTRACT
Integration of the human papillomavirus (HPV) into the host genome is a dominant feature of
invasive cervical cancer (ICC). Genomic coordinates of integration sites have been identified in
many tumors, but little is known about the nature of the cis genomic changes at these sites or
how they might promote ICC. Harnessing data from The Cancer Genome Atlas (TCGA) along
with patient-matched long-read sequencing of HPV integration sites will define novel
genes/pathways affecting ICC outcome. Aim 1 will define HPV integration sites in the TCGA-
MCW cervical cancer cohort using newly developed HPV DNA capture for long-read sequencing.
Once identified, we will annotate each integration site using TCGA data sources that document
complex rearrangements, copy number variation, clonality, loss-of-heterozygosity, epigenetic
signature, gene expression, and chimerism. Characteristics of integration sites found by this in-
depth annotation will enable us to prioritize putative integration driver genes to be further studied
in Aim 2, when we will establish the biological relevance of a few genes influenced by our high-
priority HPV integration sites. Using a panel of available cervical cancer cell lines, we will then
characterize the functional consequences of manipulating those genes whose functions in
cervical cancer have yet to be determined. The proposed study is expected to identify
downstream molecular drivers of specific HPV integration sites, thus revealing novel ICC-specific
therapeutic vulnerabilities that may be targeted for treatment.

## Key facts

- **NIH application ID:** 10042465
- **Project number:** 1R21CA241013-01A1
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Janet S. Rader
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $401,115
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10042465

## Citation

> US National Institutes of Health, RePORTER application 10042465, Defining HPV integration sites of unknown significance in invasive cervical cancer (1R21CA241013-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10042465. Licensed CC0.

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