# Project 3-- Determining biological and viral factors associated with clinical progression of cervical dysplasia in HIV-infected women

> **NIH NIH U54** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $160,894

## Abstract

Abstract
 High-risk human papillomaviruses (HR HPVs) are the causative agent for cervical cancer, with more than
80% of cases clustered in low and middle income countries (LMIC), and a further concentration in African
countries like Kenya and Uganda. There are preventive vaccines against HPV, but less than 2% of the world’s
target population has received them. This leaves millions of women at risk for cervical cancer. We need to
understand how HR HPV affects its host cell, dysregulates its environment, and, in regions with high rates of co-
infection of HR HPV and HIV, synergizes with HIV to drive cancer development and progression in women.
 The greatest clinical risk factor for cervical cancer development is a persistent HR HPV infection. When
HR HPV infects the cervix, it changes the typical, sequential activation of cellular growth and differentiation
pathways both to support the HR HPV infection and to foster cancer development. In the presence of HIV, the
pathways and functions of HR HPV infected host cells are further disrupted, leading a more rapid progression to
cancer. We hypothesize that HR HPV infections manifest in predictable cellular gene expression changes that
are detectable in cervical samples, biopsy tissues, and peripheral blood. With HIV co-infection, we hypothesize
an additional, overlapping subset of augmented or unique gene expression changes are also detectable. As a
collective, these changes can serve as functional biomarkers to prospectively identify precancerous lesions and,
in the context of her HIV status, to stratify a woman’s future cervical cancer risk. Identifying and validating these
biomarkers is the goal of Specific Aim 1.
 In addition to cellular biomarkers that predict cancer risk, the type and variant of HR HPVs is an important
predictor of morbidity and mortality associated with a cervical cancer diagnosis. Currently, there is a lack of
foundational data on the genetic landscape of variants of HPV 16, the most common HR HPV type in invasive
cervical cancers in Kenya and Uganda. We hypothesize that specific HPV 16 variants add to this region’s cervical
cancer risk; generating detailed data on HPV 16 variants is the goal of Specific Aim 2.
Our specific aims are: (1) Determine differences in host gene expression that prospectively discriminate
among HIV+ and HIV- women the risk for cervical dysplasia and precancerous lesions. We will leverage the
synchronous collection of cervical swabs and tissue, blood, and a clinical exam by visual inspection to quantify
host gene expression changes linked to pathology. (2) Determine the HPV 16 variants found in HIV+ and HIV-
women. We will investigate HPV 16 variants and conduct whole genome sequencing to create a detailed picture
of HPV 16 genetic polymorphisms. Through investigations of HR HPV, its host cells, and HR HPV in the context
of HIV, we will determine the biologic and virologic signatures designating a HIV+ or HIV- woman at risk for
cervical cancer development...

## Key facts

- **NIH application ID:** 10477371
- **Project number:** 5U54CA254518-03
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Rachel Adria Katzenellenbogen
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $160,894
- **Award type:** 5
- **Project period:** 2020-09-07 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10477371

## Citation

> US National Institutes of Health, RePORTER application 10477371, Project 3-- Determining biological and viral factors associated with clinical progression of cervical dysplasia in HIV-infected women (5U54CA254518-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10477371. Licensed CC0.

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