Precision Medicine Strategies in Otolaryngology

Head and neck cancers, as well as some other otolaryngology-related conditions, represent an opportunity to use precision-guided therapies. “This is because many oral cavity and oropharynx tumors are easily accessible for serial tissue biopsy compared to tumors in other bodily areas that are anatomically sequestered,” said Rajarsi Mandal, MD, assistant professor of otolaryngology-head and neck surgery at Johns Hopkins School of Medicine, and director of the Head and Neck Cancer Immunotherapy Research Program at the Bloomberg-Kimmel Institute for Cancer Immunotherapy in Baltimore. “Access to tumor tissue from the head and neck allows for interrogating tumor-specific genetic and immunologic vulnerabilities. Subsequent targeted therapies can then be tailored to individual patients.”

Several factors are driving increased interest in precision medicine in head and neck cancer. First, there has been a 60% increase in head and neck cancer incidences, from 39,000 to 59,000, between 2005 and 2015 in the United States. This is partially due to a rise in HPV-related head and neck cancer, associated with stable HPV-negative or unrelated head and neck cancer incidence, said Antonio Jimeno, MD, PhD, professor of medical oncology at the University of Colorado School of Medicine in Aurora. And, although cigarette smoking has declined, use of alternative tobacco products such as chewing tobacco, vaping products, and cigars has increased. The discovery of immunotherapies, which has opened up new therapeutic avenues for the first time in 10 years, is also driving interest in precision medicine.

Precision medicine can also be applied to nasal and sinus disorders. “We are using it to improve three aspects of patient care: diagnostics, prognostics, and therapeutics,” said Benjamin S. Bleier, MD, associate professor of otolaryngology at Harvard Medical School and director of endoscopic skull base surgery at Massachusetts Eye and Ear in Boston. “We determine which substrates within a patient we can harness. For a cancer patient, that might include sampling their tumor or lymph nodes. In chronic sinusitis, we might sample inflamed tissue, mucus, or exosomes. We can then look at proteomics, transcriptomics, and genetics. By using these techniques, we can partition patients into categories that help us address these three aspects.”

Hearing loss is also uniquely positioned for the application of precision medicine strategies because it is commonly caused by a single genetic mutation, and relatively simple precision medicine tools such as population-specific gene panels can typically detect it, said Oliver F. Adunka, MD, FACS, professor and director of otology, neurotology, and cranial base surgery in the department of otolaryngology, head and neck surgery at The Ohio State University Wexner Medical Center in Columbus.

Pamela Roehm, MD, PhD, professor and director in the division of otology and neurotology at the Lewis Katz School of Medicine at Temple University in Philadelphia, said hundreds of different genetic causes of hearing loss are known, with more than 20 recently identified using next-generation sequencing (NGS).

Identifying genes associated with different types of hearing loss in children is helpful in predicting prognosis of hearing loss, especially in situations where hearing loss may significantly progress with time, said Charles Yates, MD, neurotologist in the department of otolaryngology-head and neck surgery at Riley Children’s Health in Indianapolis, Ind.