# The Impact of Biologic Aging on Immunity-Related Cervical Cancer Outcome Disparities Among Women Living with HIV in Zambia

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $760,825

## Abstract

Project Summary/Abstract
Cervical cancer disproportionately affects women of color from low-socioeconomic geographical locations.
Locations, such as sub-Saharan Africa, can also have a high incidence of Human Immunodeficiency Virus (HIV)
infection, and access to cervical cancer screening is generally limited for women living in these underserved
communities. Furthermore, People Living with Human Immunodeficiency Virus (PLWH) have evidence of
premature aging, which could contribute to cervical cancer progression and responses to chemoradiation therapy
(CRT). CRT is the standard of care for locally advanced cervical cancer, and older women (≥52 years of age)
treated with CRT have worse side effects than younger (<52 years) women, suggesting that advanced age may
influence clinical outcomes from CRT for cervical cancer. Many of the hallmarks of cancer, including
tumorigenesis, tumor maintenance, therapy resistance, and immune evasion, are regulated by epigenetic
changes in DNA (e.g., DNA methylation). DNA methylation levels are correlated with (1) chronological clocks,
which estimate the age of a sample/patient, or (2) biological clocks, a widely accepted measure of where an
individual is in their lifespan, regardless of chronological age, which can be reflective of disease morbidity and
mortality risk. Indeed, the biological age of PLWH (i.e., HIV-mediated epigenetic age) is advanced up to 20 years
beyond chronological age; however, studies examining epigenetic aging in PLWH have not evaluated premature
aging in PLWH with cervical cancer, nor the contribution, if any, of oncologic therapy on premature aging.
Preliminary data comparing women living with HIV(WHIV) vs. HIV-negative cervical cancer patients indicate that
biological aging, defined using patterns of methylation that accumulate on host DNA over time, was significantly
accelerated in WHIV vs. HIV-negative cervical cancer patients, and this accelerated aging was significantly
associated with mortality after cancer diagnosis. The proposed study will test the hypothesis that a biomarker of
aging can be identified and will correlate with systemic and tumor immunologic phenotype and function that can
be used, in the future, to select WHIV and cervical cancer for novel therapeutic regimens. In Aim 1, differences
in DNA methylation will be compared between WHIV vs. HIV-negative patients with cervical cancer. Aim 2 will
focus on measuring systemic and tumor immune cell phenotype, function, and repertoire that will be correlated
with biologic age at pre-CRT and 1 year post-CRT. Furthermore, Aim 3 will focus on determining an association
of longitudinal (pre-CRT and 1-year post-CRT), biologic age changes with clinical outcomes. Results from the
proposed work are expected to elucidate how oncologic treatment in the setting of immunosuppression due to
HIV infection impacts the aging process and, through detailed interrogation of immune cells, to link aging to
underlying biological features that may ex...

## Key facts

- **NIH application ID:** 10931755
- **Project number:** 5R01CA284623-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Anna Coghill
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $760,825
- **Award type:** 5
- **Project period:** 2023-09-19 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10931755

## Citation

> US National Institutes of Health, RePORTER application 10931755, The Impact of Biologic Aging on Immunity-Related Cervical Cancer Outcome Disparities Among Women Living with HIV in Zambia (5R01CA284623-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10931755. Licensed CC0.

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