# Pursuing molecular biomarkers to guide adjuvant therapy for HPV+ head and neck cancers after transoral robotic surgery

> **NIH NIH UH2** · UNIVERSITY OF PENNSYLVANIA · 2022 · $265,891

## Abstract

PROJECT SUMMARY
This proposal aims to optimize therapy for human papilloma virus-related (HPV+) squamous cell carcinomas of
the head and neck (HNSCCs), which are rapidly increasing in incidence. The relatively favorable prognosis for
the HPV+ subtype of HNSCC has justified ongoing efforts to de-intensify their treatment with high dose
radiation and cisplatin, whose toxicities can leave lifelong disabilities in survivors. A recently popularized
approach to therapy de-escalation is transoral robotic surgery (TORS), which has markedly altered practice
patterns for this disease and allowed for reduction in cisplatin use and radiation dosing relative to nonsurgical
therapy. However, poor ability to stratify recurrence risk after TORS is a key barrier to both safely de-escalating
adjuvant therapy for typical HPV+ HNSCCs and intensifying treatment for certain cases that are predisposed to
lethal outcome. This proposal seeks to fill this knowledge gap by leveraging a unique set of archival HPV+
HNSCC specimens from patients treated by TORS to pursue novel molecular biomarkers of treatment
response and prognosis. Our studies of older cohorts with widely variable treatment suggest worse outcomes
for HPV+ HNSCCs with high oxidative metabolic gene expression, reduced E2F target gene upregulation, and
lower viral E6 oncogene expression. Thus, our overall hypothesis is that genetic variants and expression
profiles of both host and viral genes will allow prospective discrimination of HPV+ HNSCCs at risk of lethal
outcome after TORS-based therapy. To test this hypothesis, Aim 1 will identify host and viral expression
profiles distinguishing HPV+ HNSCCs that recur after TORS. Case-control analyses will be applied to a cohort
of 634 TORS-treated HPV+ HNSCCs with uniquely long-term follow-up in order to identify viral and host genes
differentially expressed in tumors that later recurred. Recurrent cases will be matched to nonrecurrent controls
based on stage, adjuvant therapy, and follow-up. Transcriptomic analysis will be followed by protein level
validation for select differentially expressed genes. Aim 2 will define genetic traits of HPV+ HNSCCs that recur
after TORS and pursue a multi-marker stratifier of recurrence risk. Whole exome sequencing will be used to
identify somatic mutations and copy number alterations that distinguish tumors that recurred from nonrecurrent
controls. In addition, viral genome sequencing will be used to assess for viral subtypes, sub-lineages, and
nonsynonymous SNPs that are over-represented in recurrence-prone tumors. Genetic traits associated with
treatment failure will be integrated with transcriptomic data to develop a multi-marker signature that stratifies
HPV+ HNSCCs for lethal recurrence risk. This assessment of molecular traits that distinguish tumors with high
recurrence risk after TORS-based therapy will create a discrete panel of molecular features that can be tested
in large cohorts, leading to creation of strong prognost...

## Key facts

- **NIH application ID:** 10357120
- **Project number:** 1UH2CA267502-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Devraj Basu
- **Activity code:** UH2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $265,891
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10357120

## Citation

> US National Institutes of Health, RePORTER application 10357120, Pursuing molecular biomarkers to guide adjuvant therapy for HPV+ head and neck cancers after transoral robotic surgery (1UH2CA267502-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10357120. Licensed CC0.

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