# Genomic Stratification and Targeting of HPV+ Cancer

> **NIH NIH R03** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $160,000

## Abstract

PROJECT SUMMARY
Human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) is increasing in
incidence, particularly among younger individuals. About 85% of these patients respond well to the current
standard-of-care treatments that include radiotherapy (XRT), but many have high morbidity due to long-term
treatment related side effects. De-escalation protocols have been proposed, and are being evaluated, in order
to reduce treatment-related morbidity without compromising the observed high survival rates. However, some
patients exhibit poor response to standard therapy, making the implementation of de-escalation protocols
challenging. The good outcomes among HPV+ OPSCC patients are believed to be determined by their higher
response to XRT, but the reasons for lack of response among some individuals are unknown. There is an
urgent need to develop biomarkers for identification of treatment resistant individuals. This would allow safe
implementation of de-intensification protocols for low risk patients, and discovery of alternative therapeutics for
treatment resistant patients. HPV+ OPSCC is genomically distinct from HPV negative tumors, and recent
studies have characterized the spectrum of genomic alterations in these tumor types. However, these genomic
analyses have not led to the clinical implementation of any genomic or molecular biomarkers for HPV+
OPSCC. We have analyzed genomic data from The Cancer Genome Atlas (TCGA) project for genes related to
HPV function and identified a signature for poor outcome in HPV+ OPSCC. This signature is robust across
multiple validation cohorts and is associated with XRT resistance in cell lines. We hypothesize that this
signature identifies an important and new aspect of HPV biology that can be utilized for patient stratification
and treatment personalization. We propose to optimize this biomarker signature for clinical use, use the
underlying biology to understand the mechanisms driving sensitivity to XRT, and test new approaches to
sensitize HPV+ tumors to XRT.

## Key facts

- **NIH application ID:** 9857590
- **Project number:** 5R03DE028381-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Curtis Pickering
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $160,000
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857590

## Citation

> US National Institutes of Health, RePORTER application 9857590, Genomic Stratification and Targeting of HPV+ Cancer (5R03DE028381-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9857590. Licensed CC0.

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