Immunotherapy
For Head and Neck Cancer

How is Immunotherapy for Head and Neck Cancer Changing the Outlook for Patients?

Reviewed by:

Ezra Cohen, MD, FRCPSC, FASCO
University of California, San Diego

Immunotherapy for head and neck cancer provides exciting new treatment options for patients, especially those with HPV-related cancers, and without the potentially devastating side effects of conventional treatments.

“Head and neck cancer” is a collective term that includes several different types of cancers. Cancers of the head and neck are categorized by the area in which they begin. This includes the mouth (oral cavity), throat (pharynx), voice box (larynx), sinuses and nose cavity, and salivary glands.

The most common type of head and neck cancer is squamous cell carcinoma of the head and neck (HNSCC). Most HNSCC begins in the layer of flat cells (the epithelium) which line the structures of the upper aerodigestive tract, including the mouth, throat, and voice box. HNSCC accounts for about three to five percent of all cancers in the United States, where, in 2023, an estimated 67,000 people will be diagnosed with head and neck cancer and approximately 15,000 will die of the disease. Globally, there were an estimated 890,000 cases in 2018 along with 450,000 deaths. The five-year survival rate of patients with head and neck cancer is about 60 percent.

Environmental risk factors for head and neck cancers include tobacco use, heavy alcohol consumption, prolonged sun exposure, and certain viruses, including human papilloma virus (HPV) and Epstein-Barr virus (EBV).

In particular, HPV infection is a risk factor for oropharyngeal cancer (cancer of the middle of the throat, including the tonsils and base of tongue). The overall incidence of HPV-positive head and neck cancers is rapidly increasing in the U.S., while the incidence of HPV-negative (primarily tobacco- and alcohol-related) cancer is decreasing. While a strong causal relationship has been established between HPV type 16 and the development of oropharyngeal cancer, other HPV types have been associated with oropharyngeal cancer as well. HPV-related head and neck cancer has a unique risk factor profile, and a more favorable prognosis than tobacco or alcohol induced HNSCCA. One HPV vaccine is approved for the prevention of HPV-related head and neck cancers. 

Preventive Vaccines

• Gardasil-9®: a vaccine approved for the prevention of infection by HPV types 16, 18, 31, 33, 45, 52, and 58, and for the prevention of genital warts caused by HPV types 6 or 11; can help prevent the development of HPV-related head and neck cancers

Though head and neck cancer is generally considered to be highly treatable and curable with surgery or radiation when detected in early stage, other options are needed for patients.

Head and Neck Cancer Treatment Options

Treatment for head and neck cancer depends on individual factors, including the exact location of the tumor, stage of the tumor, and a person’s general health. These conventional treatments for head and neck cancer (surgery, radiation, and chemotherapy) may be used alone or in combination, depending on stage and location.

Head and neck cancer is highly curable—often with single-modality therapy (surgery or radiation)—if detected early. More advanced head and neck cancers are generally treated with various combinations of surgery, radiation, and chemotherapy. With any treatment plan, the goal is not only to remove the cancer, but also to preserve the functions of the structures involved in speaking, swallowing, and expression.

Immunotherapy is class of treatments that take advantage of a person’s own immune system to help kill cancer cells. There are currently four approved immunotherapy options for head and neck cancer.

Targeted Antibodies

• Cetuximab (Erbitux®): a monoclonal antibody that targets the EGFR pathway; approved for subsets of patients with advanced head and neck cancer, including as a first-line therapy

Immunomodulators

• Dostarlimab (Jemperli): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced head and neck cancer that has DNA mismatch repair deficiency (dMMR)
• Nivolumab (Opdivo®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced head and neck cancer
• Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced head and neck cancer, including as a first-line therapy

Head and neck cancer patients with advanced disease should consider participating in a clinical trial if eligible.

CRI’s Impact in Head and Neck Cancer

At CRI, we have dedicated funding, fellowships, and grants to support scientific research into the connection between cancer and viruses, especially in head and neck cancers.

• In the late 1960s, CRI-supported scientists Ted Boyse, Herbert Oettgen, and Lloyd J. Old found evidence to link the Epstein-Barr virus (EBV) and nasopharyngeal cancer, giving the field one of the earliest indications of a bridge between a virus and human cancer.
• From the 1970s until his death in 2016, CRI supported the work of George Klein at the Karolinska Institute in Sweden on the relationship between EBV and cancer.
• Since 1994, CRI has given out more than $4 million dollars for human papillomavirus (HPV) research. This has led to a number of clinical trials testing HPV vaccines, including one that was FDA approved in 2006 (Gardasil).
• In 2008, CRI funded John C. Herr, of the University of Virginia, to study CABYR as a biomarker for lung and head and neck squamous cell carcinomas.
• In 2015, the CRI Anna-Maria Kellen Clinical Accelerator launched a clinical trial that seeks to bolster anti-PD-L1 and anti-CTLA-4 combination immunotherapy through the use of an adjuvant designed to activate innate immune responses in various advanced accessible solid tumors.

Explore CRI’s current funding for head and neck cancer research in our funding directory.