# Immunogenetic determinants of HPV-related head and neck cancer in Veterans

> **NIH VA I01** · MICHAEL E DEBAKEY VA MEDICAL CENTER · 2020 · —

## Abstract

While numbers of tobacco-associated head and neck squamous cell carcinoma (HNSCC) sharply declined
during the latter half of the 20th century, incidence of human papillomavirus (HPV)-associated HNSCC
specifically oropharyngeal cancer (OPC), which like cervical cancer is currently thought to be predominantly an
HPV-related cancer, has sharply increased. The number of persons exposed to HPV is far greater than the
number who ultimately develop HPV-related cancers, thus heritable genetic factors as well as the interplay
between genetic and environmental factors likely modulate observed inter-individual differences in risk.
However, the specific immune-related genetic variants helping to modulate individual susceptibility are largely
unknown. We hypothesize that variation in immune-related genes likely plays a role in the host susceptibility to
development of OPC in the VA population. We further hypothesize that integrative bioinformatic analysis can
be used to identify gene variants associated with increased risk of OPC, particularly in those with confirmed
HPV infection. Although immune genes are expected to play a large role in virally-associated OPC, they may
also play a role in risk of non-oropharynx head and neck squamous cell cancer (non-OPC HNSCC) which is
overwhelmingly associated with smoking and alcohol abuse because both OPC and non-OPC HNSCC
increase 1) chronic inflammation, a pro-carcinogenic state, and 2) are associated with immune evasion
associated with oncogenesis which both impact cancer risk partially by mediating immune gene signaling.
In the first Aim we will use validated methods to phenotype four distinct study cohorts within the MVP: OPC
both overall and among those with HPV infection (HPVOPC), non-OPC HNSCC, and matched cancer-free
controls. In order to identify confirmed HPV-related OPC (HPVOPC), we will obtain p16 immunohistochemistry
data from pathology reports via chart review. We will include in our source population to select both cases and
controls all participants in MVP with genetic array data. We will define (1) demographics (e.g., age, gender,
race/ethnicity from CDW) and (2) clinical comorbidities and environmental and behavioral risk behaviors (e.g.,
BMI, diabetes, smoking, and alcohol use from CDW and MVP surveys). Four randomly selected controls with
a VA visit in the same year the case was first identified (index date) will be frequency matched by age,
race/ethnicity, gender, geographic region, year of first VA use in study period, and first VA enrollment during
study period for each cancer group.
In the second Aim we will perform parallel integrative genetic analysis of the association between
polymorphisms in multiple pre-selected immune genes and all OPC, HPVOPC (subset that are pathology-
confirmed HPV positive by p16 immunohistochemistry), and non-OPC HNSCC. We will identify shared and/or
unique risk variants across HPVOPC, OPC overall and non-OPC HNSCC. We will also assess for gene-gene
and gene-environ...

## Key facts

- **NIH application ID:** 9940681
- **Project number:** 5I01BX004420-02
- **Recipient organization:** MICHAEL E DEBAKEY VA MEDICAL CENTER
- **Principal Investigator:** Donna Lorraine White
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9940681

## Citation

> US National Institutes of Health, RePORTER application 9940681, Immunogenetic determinants of HPV-related head and neck cancer in Veterans (5I01BX004420-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9940681. Licensed CC0.

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