Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Dissecting NF-kB pathway in HPV-associated head and neck cancer

Award Number: R01DE031297
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2027

Group Awards By:

View Award Description

Dissecting NF-kB pathway in HPV-associated head and neck cancer - Project summary The incidence of HPV-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) has dramatically increased over the last few decades and continues to rise. Despite the magnitude of this epidemic, mechanisms of HPV-driven carcinogenesis in HPV+ HNSCC have not been thoroughly investigated. Compared to patients with tobacco-associated HNSCC, those with HPV+ HNSCC have increased overall survival and higher response to treatment, which usually consists of chemo- and radiation therapy; however, survivors frequently suffer from treatment’s toxic side effects, such as swallowing and speech dysfunction. In addition, approximately 25% of HPV+ HNSCC patients develop recurrent or metastatic disease, for which there are limited treatment options. A pressing goal in head and neck oncology is to decrease the morbidity of therapy for HPV+ HNSCC through treatment de-escalation. However, biomarkers that identify HPV+ patients with good prognosis, who may be appropriate for de-escalation therapy, are lacking. Using three independent cohorts, we found that constitutively active NF-κB (usually arising from genetic defects in NF-κB regulators, including TRAF3 and CYLD) correlates with survival and should be explored as a prognostic biomarker in HPV+ HNSCC. Our preliminary data suggest that survival benefits of patients, whose tumors harbor overactive NF-κB, are attributed to better tumor response to therapy and that both, inherent NF-κB-driven tumor characteristics (e.g. downregulated expression of oxidative stress response, NRF2 target genes), as well as a distinct tumor microenvironment (e.g. elevated number of tumor infiltrating CD4+ T cells), may contribute to increased sensitivity of NF-κB active tumors to radiation. We previously reported that mutations in TRAF3 and CYLD were associated with a lack of HPV integration, leading us to hypothesize that NF-κB activation may enable cells to maintain HPV episomes. Since the canonical HPV carcinogenesis model depends on HPV integration, we also hypothesize that activation of NF-κB may be critical for an alternative mechanism of HPV carcinogenesis driven by HPV episomal maintenance. To explore our hypothesis, in Specific Aim 1, we will investigate the impact of NF-κB signaling on HPV gene expression and episomal maintenance. In Specific Aim 2, we will explore the significance of NF-κB pathway on cellular proliferation, survival, and cellular transformation in response to HPV. Finally, Specific Aim 3 will explore mechanisms of NF-κB mediated radiation sensitivity in HPV+ HNSCC.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $458,709 )
2026	2026	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Oral Diseases and Disorders Research	000	4	1/13/2026	NON-COMPETING CONTINUATION	$458,709
														Subtotal = $458,709

Issue Date FY: 2025 ( Subtotal = $509,676 )
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Oral Diseases and Disorders Research	000	3	12/31/2024	NON-COMPETING CONTINUATION	$458,709
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Oral Diseases and Disorders Research	001	3	5/6/2025	NON-COMPETING CONTINUATION	$50,967
														Subtotal = $509,676

Issue Date FY: 2024 ( Subtotal = $536,605 )
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Oral Diseases and Disorders Research	000	2	11/28/2023	NON-COMPETING CONTINUATION	$492,801
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Oral Diseases and Disorders Research	001	2	6/6/2024	NON-COMPETING CONTINUATION	$43,804
														Subtotal = $536,605

Issue Date FY: 2023 ( Subtotal = $488,746 )
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Oral Diseases and Disorders Research	000	1	2/28/2023	NEW	$488,746
														Subtotal = $488,746

Grand Total All Awards = $1,993,736

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Dissecting NF-kB pathway in HPV-associated head and neck cancer

Award Number: R01DE031297

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/01/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer