# Stress keratin 17 and CD4/8 ratio as prognostic markers in HIV-related anogenital squamous cell precancers and cancers (Biospecimens/Biocohort)

> **NIH NIH P30** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $239,001

## Abstract

Stress keratin 17 and CD4/8 ratio as prognostic markers in HIV-related anogenital squamous cell
precancers and cancers
ABSTRACT
Scientific Rationale: Despite the decrease in mortality people living with HIV (PLWH) due to combination
antiretroviral therapy, anogenital human papillomavirus (HPV)-related squamous dysplasia and cancer are
more common among PLWH.1–9 There is a lack of prognostic markers to risk stratify anogenital squamous
dysplasia and cancer among PLWH. There is a critical need to identify prognostic markers (circulating
blood markers and/or epithelial markers) to predict disease development and progression particularly in
PLWH.
Hypothesis: Our central hypothesis is that K17 expression may correlate with circulating low CD4/CD8 T
cell ratio, reflective of a suppressive tumor microenvironment, in HIV-associated precancers and cancers of
the anogenital tract, and, therefore, predict prognosis.
Project Design: In Aim 1, we will test whether a biomarker we found upregulated in response to HPV
infection in preclinical models (keratin 17; K17) correlates with progression, regression and/or prognosis
among PLWH with anogenital precancers and cancers. We will use immunohistochemistry as well as
cutting edge spatial single cell multiplex imaging to profile the tumor microenvironment and spatial
relationships in AIDS and Cancer Specimen Resource (ACSR) tissue microarrays, and our own tissue
microarrays among anogenital dysplasia and cancers from HIV+ and HIV- patients. In Aim 2, we will
determine if circulating CD4/8 T cell ratio and/or other immune cell subsets predict clinical outcomes in
anogenital precancers and cancers.
Relevance: Our study will test two potential markers of prognosis of anogenital disease among PLWH and
better define the tumor microenvironment that allows for disease progression in these patients.
This is a collaborative P30 Administrative Supplement Application from Drs. Evie Carchman, Megan
Fitzpatrick, Huy Dinh, Nathan Sherer, Lisa Barroilhet, and Paul Lambert. Our multidisciplinary team
includes a junior gynecologic pathologist with experience in HPV molecular virology and dysplasia studies
among PLWH with HIV/AIDS (Co-Project leader: Fitzpatrick), a colorectal surgeon with expertise in the
treatment of various HPV-associated anogenital diseases and expertise in use of mouse anal cancer
preclinical models (Co-Project leader: Carchman), a tenured gynecologic oncologist with clinical and
research experience in detection and treatment of HPV-related gynecologic cancers (Barroilhet), a
computational biologists with track record in evaluating complex tumor immune microenvironments in
multiple cancer types, including HPV-related cancers (Dinh), a researcher with expertise in HIV (Sherer),
and a senior expert in HPV infection and HPV-related cancers whose lab has developed multiple preclinical
mouse models for anogenital cancer (Lambert).

## Key facts

- **NIH application ID:** 10620051
- **Project number:** 3P30CA014520-48S7
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** HOWARD H. BAILEY
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $239,001
- **Award type:** 3
- **Project period:** 2022-09-20 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10620051

## Citation

> US National Institutes of Health, RePORTER application 10620051, Stress keratin 17 and CD4/8 ratio as prognostic markers in HIV-related anogenital squamous cell precancers and cancers (Biospecimens/Biocohort) (3P30CA014520-48S7). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10620051. Licensed CC0.

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