# Comprehensive Cancer Center Support Grant

> **NIH NIH P30** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $211,731

## Abstract

PROJECT SUMMARY/ABSTRACT
Cervical cancer is the fourth most common and third most fatal cancer among women worldwide. Cervical cancer
is an AIDS-defining illness and the most common cancer among women living with HIV (WLWH) globally.
Overall, WLWH have a higher risk of HPV acquisition, lower risk of HPV clearance, higher incidence of high
grade lesions (HGSIL), reduced regression from HGSIL to normal, and higher incidence of cervical cancer
compared to women without HIV. However, little is known about the biological mechanism of cervical pre-cancer.
It is estimated that there are 250,000-1 million new cases of cervical pre-cancer each year in the U.S. requiring
treatment for these pre-cancerous lesions. Even with the WHO’s 90-70-90 cervical cancer elimination strategy,
where they expect to treat 90% of the pre-cancer women, the unwanted effects of invasive treatment should not
be overlooked. Not all pre-cancers progress to cancer and identifying biomarkers associated with progression
could help with treatment algorithms (specifically in HIV). One compelling hypothesis is that additional molecular
events besides human papillomavirus (HPV) are required for cervical pre-cancer development as well as
progression to high grade lesions and biological aging is a likely event at the molecular level. Several studies
suggest that HIV induces alterations of the host biology and in doing so these alterations can accelerate
biological aging. HIV-related aging potentially results in impairing the immune system so that it can no longer
control the risk for cancer. Immune cell profiles using methylation-derived neutrophil-to-lymphocyte (NLR) and
leukocyte-to-monocyte ratio (LMR) have been shown to be associated with risk of different cancers, including
HPV-driven oropharyngeal cancer; however, there are no reports of studies in pre-cancer, which is a pre-cursor
to cancers that will have impactful prevention strategies. In the proposed study, we will examine the association
of two biomarkers of aging (aging-related inflammation and DNA methylation) with cervical pre-cancer in WLWH
and compare with HIV-negative women in two races (Black and White). To achieve the goal, we will utilize tissues
from: a) “coexisting” normal and pre-cancer lesions from each individual and b) pre-cancer progression lesion
samples collected longitudinally from the same individual from two different time-points. This design allows
validation of results using two different study designs. We will focus on the different neoplastic tissues and utilize
cell isolation techniques and nucleotide processing technologies that allow comprehensive methylation assays
to derive two biomarkers of aging, immune-cell profile (Aim 1) and biological age (Aim 2), using state-of-the-art
computational algorithms. This innovative study will bridge the gap in translating molecular knowledge of cervical
pre-cancer progression and potentially provide insights into development of aging biomarkers. There is potenti...

## Key facts

- **NIH application ID:** 11065985
- **Project number:** 3P30CA013148-51S2
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Barry P Sleckman
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $211,731
- **Award type:** 3
- **Project period:** 1997-03-28 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11065985

## Citation

> US National Institutes of Health, RePORTER application 11065985, Comprehensive Cancer Center Support Grant (3P30CA013148-51S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11065985. Licensed CC0.

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