# Improving Treatment Algorithms for Veterans with Oropharyngeal Cancer

> **NIH VA IK2** · MICHAEL E DEBAKEY VA MEDICAL CENTER · 2022 · —

## Abstract

Oropharyngeal cancer is rapidly increasing in incidence in the veteran population, fueled
largely by exposure to the human papilloma virus (HPV). Although survival for oropharyngeal
squamous cell carcinoma associated with the human papilloma virus (HPV+OPSCC) is excellent
in the general population, it remains dismal in the veteran population, with nearly 1 in 2 patients
dying of their disease within 5 years of diagnosis. This disproportionally poor survival is thought
to be driven in part by tumors which are less responsive to chemo-radiation treatment regimens.
Preliminary data from our group and others suggests this decreased treatment response may be
in part driven by tobacco exposure, which is extremely prevalent among Veterans with
HPV+OPSCC. The hypothesized mechanism of action is a tobacco induced, immunosuppressive
environment which inhibits the normal anti-tumor activity of lymphocytes and other immune cells
during cancer treatment.
 In the current proposal, we will first characterize and quantify the relative effect of tobacco
exposure on survival in Veterans with HPV+OPSCC (Aim 1). This is critical in light of the newly
implemented 8th Edition of the AJCC Staging Manual which dramatically down-stages OPSCC
based on HPV status (HPV associated vs non-HPV associated), but does not consider the
potentially critical impact of tobacco exposure on survival. Given the widespread, and extensive
tobacco exposure we and others have demonstrated in Veterans with OPSCC, this represents an
important clinical and translational first step in potentially improving survival for Veterans with this
disease.
 We will then characterize the Th1 T-lymphocyte and myeloid derived suppressor cell
(MDSC) components of the tumor immune microenvironment (TIME) in HPV+OPSCC tumors as
a function of tobacco exposure (Aim 2). This will allow us to provide support for our mechanistic
hypothesis and to define the relationship between tobacco exposure and changes in the TIME of
HPV+OPSCC. Finally, we will compare the TIME characteristics of HPV+OPSCC tumors which
fail to respond to conventional chemo-radiation treatment regimens to the TIME of HPV+OPSCC
tumors which do respond to treatment, in order to define an immune signature associated with
treatment resistance in this disease site (Aim 3). Together, these experiments will allow us to: 1)
define a clinically relevant effect size for tobacco exposure vis a vis HPV+OPSCC survival and 2)
begin to define a mechanistic link between tobacco exposure and TIME dependent treatment
response. Successful completion of the proposed research will allow us to more appropriately
prognosticate survival in Veterans with HPV+OPSCC, identify patients which may be candidates
for treatment escalation using immunomodulatory agents (i.e. checkpoint inhibitors) and patients
which should not be enrolled in clinical trials aimed at de-escalation of chemo-radiation regimens
in order to decrease normal tissue toxicity.
 In parallel with the propo...

## Key facts

- **NIH application ID:** 10425236
- **Project number:** 5IK2CX001953-03
- **Recipient organization:** MICHAEL E DEBAKEY VA MEDICAL CENTER
- **Principal Investigator:** VLAD C SANDULACHE
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10425236

## Citation

> US National Institutes of Health, RePORTER application 10425236, Improving Treatment Algorithms for Veterans with Oropharyngeal Cancer (5IK2CX001953-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10425236. Licensed CC0.

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