# Computational tumor phenotyping to interrogate treatment resistance and immune dysregulation in head and neck cancer

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $496,567

## Abstract

ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is the 7th most prevalent cancer globally,
resulting in 930,000 new cases and 467,000 deaths annually. Alongside tobacco and alcohol use, human
papillomavirus (HPV) infection contributes to HNSCC development. Regardless of their clinical stage or location,
these tumors exhibit significant heterogeneity in gene expression and treatment response. While immunotherapy
has revolutionized treatment approaches for many cancers, its impact on HNSCC remains limited. This suggests
aspects of HNSCC tumor immunology – including the role HPV plays in immune dysregulation – are not well
understood. Thus, the objective of this research is to develop, validate, and implement advanced computational
tumor phenotyping techniques to characterize HNSCC at multiple levels of biological organization. Our approach
involves high-throughput analysis of quantitative features from both radiology images (i.e., radiomics) and digital
pathology images (i.e., pathomics) to generate a multiscale depiction of the HNSCC phenotype. We hypothesize
that tumor-specific radiopathomic expression patterns of HNSCC are connected to fundamental biological and
immunomolecular processes driving therapeutic resistance. In Aim 1, the prognostic value of radiomics will be
evaluated in both HPV+ and HPV− HNSCC patients treated with radiotherapy as part of a previously conducted
prospective clinical trial (NCT01908504). Changes in radiomic expression after initial 20 Gy will be quantified via
data assimilation of PET/CT imaging and stochastic models of tumor dynamics. In Aim 2, the tumor immune
microenvironment of these patients will be characterized via pathomic analysis. Single-cell interactions will be
measured between different immune compositions and compared to single-cell transcriptomics data to gain
mechanistic insight into the genes driving pathomic expression. Radiomics (Aim 1) and pathomics (Aim 2) will
each be experimentally confirmed and mechanistically validated in novel carcinogen-induced and genetically
engineered mouse models that co-evolve with an intact immune system, where we will dissect mechanisms of
treatment resistance and interrogate immune dysregulation in mice that spontaneously develop HPV+ vs. HPV−
HNSCC. In Aim 3, our scientific findings will be independently tested in an ongoing prospective interventional
study (NCT04667585) to evaluate radiopathomic expression as a potential biomarker to guide adaptive therapy
for HPV+ HNSCC. Candidate biomarkers identified in NCT01908504 will be independently tested in
NCT04667585 to provide an unbiased evaluation of their prognostic value. The rationale for these studies is to
enhance understanding of HNSCC biology to guide improved treatment approaches for this urgent, unmet
clinical need. By leveraging innovative radiopathomic strategies, novel clinical trial data, and complementary
mechanistic interrogation, our proposed research will be an important advancement in comput...

## Key facts

- **NIH application ID:** 10856940
- **Project number:** 1R01CA289261-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Kyle Lafata
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $496,567
- **Award type:** 1
- **Project period:** 2024-06-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10856940

## Citation

> US National Institutes of Health, RePORTER application 10856940, Computational tumor phenotyping to interrogate treatment resistance and immune dysregulation in head and neck cancer (1R01CA289261-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10856940. Licensed CC0.

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