# Observational study to validate circulating HPVDNA and prognostic genomic biomarkers for diagnosis and treatment of HPV-associated OPSCC

> **NIH NIH U01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $741,313

## Abstract

The incidence of HPV-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC)
has rapidly increased over the last two decades surpassing uterine cervical cancer as the most
frequently diagnosed HPV-associated cancer in the United States by 2012. This “epidemic” is
expected to continue through 2060. Patients are typically diagnosed with metastatic nodal disease
treated with high dose radiation with concurrent cisplatin. This treatment was not designed for
HPV+ OPSCC but was based on results of trials of therapeutic escalation for HPV-negative
cancers. This aggressive treatment results in lifelong morbidity, and side effects of therapy may
also shorten lifespan. For the approximately 25% of these patients who will recur, late
identification of recurrence limits salvage options for a portion. Early detection of initial disease
and recurrences would allow less morbid therapy that may also increase survival. The head and
neck oncology community has recently focused on personalization of therapy for HPV+ OPSCC,
in particular on therapeutic de-intensification. The major stumbling block that is preventing
widespread adoption of these therapeutic strategies is inability to identify patients at low risk of
recurrence who are appropriate for less intensive therapy.
 Our group identified and piloted prognostic biomarkers and an assay for detection of treatment
response and for early detection of initial or recurrent HPV+ OPSCC. The prognostic biomarker
is based on deletion or mutations of TRAF3 or CYLD in tumors. Analysis of the TCGA cohort
revealed that survival of HPV+ OPSCC patients with TRAF or CYLD defects was significantly
better than those whose tumors lacked defects. Remarkably, HPV+ OPSCC tumors lacking
TRAF3 or CYLD defects had survival that was indistinguishable from HPV-negative patients,
suggesting that the improved survival in HPV+ OPSCC is largely attributable to the subset with
these mutations. We also have piloted detection of circulating HPVDNA using ultrasensitive digital
PCR as a measure of treatment response, predictor of recurrence, and for early detection of
recurrent disease.
 These assays that we piloted for prognostication, as well as treatment response and early
detection of initial or recurrent HPV+ OPSCC require validation before they will be clinically useful.
Here we propose to partner with MD Anderson Cancer Center to leverage an ongoing trial and
use detection of circulating HPVDNA to distinguish patients with oral HPV infection from those
with early HPV+ OPSCC. We will also conduct a prospective observational clinical trial to validate
TRAF3 and CYLD mutations as prognostic biomarkers and validate detection of circulating
plasma HPVDNA for early detection of recurrent HPV+ OPSCC. Validation of prognostic
biomarkers will aid appropriate selection of HPV+ OPSCC patients for de-intensified therapy while
also identifying those who need aggressive or novel therapies to improve survival. Validation of a
tool for prediction of...

## Key facts

- **NIH application ID:** 10458612
- **Project number:** 5U01DE029754-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Natalia Issaeva
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $741,313
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458612

## Citation

> US National Institutes of Health, RePORTER application 10458612, Observational study to validate circulating HPVDNA and prognostic genomic biomarkers for diagnosis and treatment of HPV-associated OPSCC (5U01DE029754-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10458612. Licensed CC0.

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