NIDCR Head and Neck Cancer Think Tank Summary

Date of Event: January 19, 2022, 10:00 a.m.–1:00 p.m. (EST)

Points of Contact

Background and Objectives

Head and neck cancers (HNC), the sixth leading type of cancers by incidence worldwide, arise in the oral and nasal cavities, sinuses, pharynx, larynx, and salivary glands. More than 65,000 individuals are newly diagnosed with HNC yearly in the United States. While cancer prevention programs such as tobacco control and smoking cessation have decreased the overall HNC incidence, human papillomavirus (HPV) associated oropharyngeal cancers have sharply increased in recent years. Despite improved treatment with targeted therapy and immunotherapies, overall five-year survival rate for HNC patients remains around 50-60%, and treatment of late-stage HNC causes disfiguring and severe morbidity, which compromises quality of life. The advancements of high throughput technologies and large data computation accelerated the understanding of comprehensive genomic and molecular portraits of human cancers. Unfortunately, advances in basic biology have not readily translated to clinical care, and early detection and interventional options are limited. Twelve HNC experts were invited to discuss the most critical and challenging questions in HNC research.

Key Themes and Recommendations

What are the major gaps and challenges to improve patient prognosis and responses to treatments in the head and neck clinics?

Gaps and Challenges

• Molecular classification of HNC using genomic and mutation information has not been translated to differentiate early versus late-stage cancers with aggressive and metastatic potentials.
• Most diagnosed HNC patients are at advanced disease stage with limited treatment options and modalities.
• Current diagnostic criteria and staging systems are outdated.
• Lack of predictive biomarkers due to limited statistical power in small studies, costs for genomic screening, and the time-consuming and costly nature of accruing enough patients, validation, and long-term follow-ups.

Opportunities

• Development of predictive biomarkers and monitoring clinical treatment efficacy need large trials to investigate de-escalation, immunotherapies and combinatory regimens, toxicity, and survival benefits for patients.
• Treating tumor cells with imprecise approaches and lacking research in tumor heterogeneity and plasticity.
• Need to develop patient-derived xenografts (PDX) and organoid models to support precision cancer treatment.
• To reduce health disparity, underserved populations lacking access to early and personalized diagnosis and treatment, and roles of oral and tumor microbiome, are additional gaps and opportunities in oral cancer research.

What are the major gaps and challenges in the prevention and early detection of human papillomavirus (HPV) +/- head and neck cancer?

Gaps and Challenges

• In clinics, HPV+ HNC lack early symptoms, are anatomically difficult to visualize, and early detection is hindered by lack of knowledge of precancerous lesions.
• Difficult to validate predictive biomarkers due to low incidence of HPV+ HNC in population.
• HPV vaccination uptake is low, multiple barriers to vaccination have been identified in dental practices and communities.

Opportunities

• Need for primary detection by clinical examination with biopsies and pathological assessment using standardized collection of patient’s samples and updated diagnostic criteria.
• HPV+/- cancer biomarker assays need to be developed using liquid biopsies, circulating tumor DNA, RNAs, and exosome signatures for early detection of primary cancers and recurrence, and integrated into prevention and intervention with multi-dimensional data analysis.
• Need to calibrate dentists and clinicians to conduct thorough and rigorous oral exams for early cancer detection.
• Need implementation research to increase vaccine uptake, e.g., engagement of pediatricians with communities and schools, research in imaging and biomarkers for early detection, and natural history study in high-risk population.
• mRNA vaccines and therapeutic vaccines have great potential, but more research and clinical trials are necessary for validation.

What are the best strategies, approaches, and detection methods to be developed for biomarker identification and validation in early detection and prevention?

Gaps and Challenges

• Lack of biomarkers to monitor the transition from normal tissue to hyperplasia, from dysplasia to cancer, and from inflamed but immune deficient precancer to cancer in the immunosuppressive microenvironment.
• Lack of standardized protocols for suspicious oral lesion sample collection and storage, and analytical algorithms to exclude false signals from oral cavity injury and tissue regeneration.
• The collection of serial biopsies and large biospecimens may not be realistic in clinical studies
• Challenges to design a cancer screening trial to overcome cancer visualization problems using endoscopy, deep tissue biopsy, and liquid biopsy.
• Lack of validation of potential biomarkers to exam their clinical utility for early detection and prevention of HNC.

Opportunities

• Need new technologies to discover and validate biomarkers in saliva and brush biopsy, using transcriptome, exosomes, and the oral microbiome to generate comprehensive biosignatures.
• Discovery and validation of biomarkers need dynamic and adaptive approaches using longitudinal sampling and multi-institutional trials.
• Histomorphometric analysis of tissue sections from biopsies.
• Artificial intelligence and machine learning approaches are needed to analyze multidimensional and dynamic information, including advanced algorithms, decision trees, risk stratification, and patient selection.

Attendees

Christine Chung, M.D.
Chair, Department of Head and Neck-Endocrine Oncology
H. Lee Moffitt Cancer Center and Research Institute

Nisha D’Silva, B.D.S., M.S.D., Ph.D.
Donald A Kerr Endowed Collegiate Professor of Oral Pathology
Professor of Dentistry, School of Dentistry
University of Michigan

Gypsyamber D’Souza, Ph.D.
Professor of Epidemiology
Johns Hopkins Bloomberg School of Public Health
Johns Hopkins University

Robert Ferris, M.D., Ph.D.
Director, UPMC Hillman Cancer Center
Hillman Professor of Oncology and Professor of Otolaryngology, of Immunology, and of Radiation Oncology
University of Pittsburgh School of Medicine

J. Silvio Gutkind, Ph.D.
Distinguished Professor
Chair, Department of Pharmacology, School of Medicine
Associate Director of Basic Science, Moores Cancer Center
University of California-San Diego

Antonio Jimeno, M.D., Ph.D.
Professor, Medicine-Medical Oncology
University of Colorado

Quynh-Thu Le, M.D.
Katharine Dexter McCormick and Stanley McCormick Memorial Professor
Chair, Department of Radiation Oncology
Stanford University

Fatemeh Momen-Heravi, D.D.S., Ph.D., M.P.H.
Associate Professor at the College of Dental Medicine
Herbert Irving Comprehensive Cancer Center
Columbia University

Jeffrey N. Myers, M.D., Ph.D.
Professor
Departments of Head & Neck Surgery and Cancer Biology
University of Texas MD Anderson Cancer Center

Jacques Nor, D.D.S., Ph.D.
Professor of Dentistry
Chair, Department of Cariology, Restorative Science and Endodontics, School of Dentistry
Professor of Biomedical Engineering, College of Engineering
Professor of Otolaryngology-Head and Neck Surgery, Medical School
University of Michigan

Quintin Pan, Ph.D.
Deputy Director, University Hospitals Seidman Cancer Center
Professor, Department of Otolaryngology, School of Medicine
Co-Leader, Molecular Oncology Program, Case Comprehensive Cancer Center
Case Western Reserve University

Wendell Yarbrough, M.D.
Distinguished Professor of Otolaryngology/ Head and Neck Surgery
University of North Carolina Chapel Hill School of Medicine
University of North Carolina-Chapel Hill