The purpose of this Notice is to inform potential applicants of the special interest of the National Cancer Institute (NCI) in encouraging the submission of applications that advance early detection of head and neck cancer (HNC) to apply genomics, molecular signatures, and epidemiology in clinical studies for distinguishing benign from malignant lesions. This initiative encourages discovery and development of molecular markers to combine with currently available HNC detection methods to increase sensitivity and specificity.

Background

Head and Neck Cancer (HNC), the sixth leading cancer by incidence worldwide, is a heterogeneous group of malignancies that arise in the oral and nasal cavities, paranasal sinuses, pharynx, larynx, and salivary glands. In the United States, more than 65,000 individuals are diagnosed with HNC every year. Head and neck squamous cell carcinoma (HNSCC) accounts for about 80% of all HNC; less common HNC types include adenocarcinomas (<15%), lymphomas (<5%), melanomas (<3%), and salivary gland carcinomas (<3%). The primary risk factors associated with HNC include tobacco use, alcohol consumption, and viral infections such as from Human Papilloma Virus (HPV), Epstein-Barr Virus (EBV), and Human Immunodeficiency Virus (HIV).

While cancer prevention programs such as tobacco control and smoking cessation have decreased the overall HNC incidence, a steady increase in HPV-associated tongue and oropharyngeal cancers have been identified in recent years. Despite our increased understanding of the molecular attributes and therapeutic advances in HNSCC, the five-year overall survival rate remains at about 40 to 50 percent in the past two decades. This lower survival rate is due in part to the lack of early disease detection and limited interventional options for HNC premalignancy. Indeed, HNC patients diagnosed with early-stage disease experience significantly improved survival rates and quality of life.

Early detection and diagnosis of HNC remain a significant challenge because early development of cancer may not cause any symptoms, may appear as benign lesions or may reside in deep cavities. Therefore, improvement of early detection will be a key to begin and optimize treatment. Promoting molecular biomarker research could have great potential to make a high impact on early detection and diagnosis of HNC to reduce death rates and morbidity.

Research Objectives

Cancer screening and early detection by discovering the malignancy, or its precursor lesions, at an early stage prior to the onset of symptoms, is the most effective way in controlling HNC. This NOSI seeks applications that focus on early detection of HNC by applying genomics, epigenomics, transcriptomics, proteomics, and molecular signatures to clinical studies for differentiating benign lesions from malignant ones. The initiative also encourages novel basic research for HNC cancer prevention as well as the development of molecular markers to combine with current available HNC detection methods for increasing sensitivity and specificity.

Research topics that are relevant to this NOSI include, but are not limited to:

• Discover and develop molecular signatures that will distinguish lesions that are most likely to progress to cancer from those that are unlikely to cause any harm.
• Discover and evaluate molecular biomarkers and technologies that could complement currently available clinical methods (e.g., CT, MRI, pathology) to increase sensitivity and specificity for accurately assessing risk and for detecting early-stage HNC and predicting progression.
• Develop tools and methods for detecting molecular signatures in body fluids obtained by non-invasive or minimally invasive methods for HNC detection.
• Identify and characterize factors for risk prediction or early detection of HNC, including nutrition, microbiome, immunocompetence, and oral health.
• Encourage the creation of an interdisciplinary group to conduct collaborative studies by bringing together expertise in bioinformatics and laboratory-based technologies, molecular biomarker discoveries, population cohorts, and clinical studies to validate molecular biomarkers for HNC early detection and prevention.
• Encourage longitudinal sample collection for identifying molecular signatures prior to HNC development and for studying early molecular biomarkers.
• Encourage collaborations, including international collaborations for HNC early detection for optimizing prevention strategies.
• Develop, adapt, optimize, and validate imaging-based applications and data analysis tools to enhance oral disease detection, diagnosis, and treatment.

Application and Submission Information

This notice applies to due dates on or after June 5, 2020, and subsequent receipt dates through January 8, 2022.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcements through the expiration date of this notice.

Activity Code	FOA Title	First Available Due date
R03	PA-19-052 NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed)	June 16, 2020
R21	PA-19-053 NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)	June 16, 2020
R21	PA-19-054 NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)	June 16, 2020
R01	PA-19-055 Research Project Grant (Parent R01 Clinical Trial Required)	June 5, 2020
R01	PA-19-056 NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)	June 5, 2020

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

NOTE: For funding consideration, applicants must include NOT-CA-20-031 (without quotation marks) in the Agency Routing Identifier field (box 4b) of the SF424 R&R form. Applications without this information in box 4b will not be considered for this initiative.

Although NCI and NIDCR is not listed as a Participating Organization in all the FOAs listed above, applications for this initiative will be accepted.

Applications nonresponsive to terms of this NOSI will be withdrawn from consideration for this initiative.

Please direct all inquiries to the contacts in Section VII of the listed funding opportunity announcements with the following additions/substitutions:

Scientific/Research Contact(s)

For inquiries related to cancer biomarker research, risk assessment, early detection, and prevention, please contact:
Wendy Wang, Ph.D., M.Sc.,
National Institutes of Health
National Cancer Institute (NCI)
Telephone: (240) 276-7117
Email: wangw@mail.nih.gov

Karl Krueger, Ph.D.,
National Institutes of Health
National Cancer Institute (NCI)
Telephone: (240) 276-7026
Email: kruegerk@mail.nih.gov

Matthew Young, Ph.D.,
National Institutes of Health
National Cancer Institute (NCI)
Telephone: (240) 276-5846
Email: matthew.young@nih.gov

Sudhir Srivastava, Ph.D., MPH,
National Institutes of Health
National Cancer Institute (NCI)
Telephone: (240) 276-7040
Email: srivasts@mail.nih.gov

For inquiries related to global health research, please contact:
Paul C Pearlman, Ph.D.,
National Institutes of Health
National Cancer Institute
Center for Global Health
Telephone: (240) 276-5354
email: paul.pearlman@nih.gov

For inquiries related to imaging of oral lesions, please contact:
Solita Chiayeng Wang, Ph.D.,
National Institutes of Health
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: (301) 827-4647
Email: chiayeng.wang@nih.gov

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Amy R. Bartosch
Office of Grants Administration
National Cancer Institute (NCI), NIH
Telephone: 240-276-6375
Email: amy.bartosch@nih.gov

Diana Rutberg
Grants Management Branch
National Institute of Dental and Craniofacial Research (NIDCR), NIH
Telephone: 301-594-4798
Email: rutbergd@mail.nih.gov