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Immunotherapy for Head and Neck Cancer

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  • Head and Neck Cancer
  • Treatment Options
  • CRI's Impact
  • Clinical Trials

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

Reviewed By: Andrew Sikora, M.D., Ph.D.
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Baylor College of Medicine, Houston, TX
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"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 (HNSCCA). Most HNSCCA 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. HNSCCA accounts for about 3% to 5% of all cancers in the United States, where, in 2018, an estimated 65,000 people were diagnosed with head and neck cancer and aproximately 14,000 died 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%.

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.

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.

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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.

There are currently three 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

  • 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

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

Find a head and neck cancer clinical trial

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. Since 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.

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

Donate to head and neck cancer research

Featured Patient

I am fearfully and wonderfully made, no weapon formed against me shall prosper.

K.c. Dill
Lung Cancer  |  Diagnosed 2015
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Sacha Gnjatic, Ph.D.
Icahn School of Medicine at Mount Sinai
Clinical Accelerator  |  2015
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CRI Immunotherapy Patient Summit in San Diego on June 29, 2019 

Head and Neck Cancer Statistics

75% Of head and neck cancers are caused by tobacco and alcohol use
890K Newly diagnosed patients each year globally

Head and Neck Cancer Clinical Trial Targets

Discover the different proteins, pathways, and platforms that scientists and physicians are pursuing to develop new cancer treatments. Use this information to consider your clinical trial options.

Therapies
  • Targeted Antibodies
  • Cancer Vaccines
  • Adoptive Cell Therapy
  • Immunomodulators
  • Oncolytic Virus Therapy

Targeted antibodies are proteins produced by the immune system that can be customized to target specific markers on cancer cells in order to disrupt cancerous activity, especially unrestrained growth. Antibody-drug conjugates (ADCs) are equipped with anti-cancer drugs that they can deliver to tumors. Bi-specific T cell-engaging antibodies (BiTEs) bind both cancer cells and T cells in order to help the immune system respond more quickly and effectively. Antibody targets under evaluation in head and neck cancer clinical trials include:

  • DLL/Notch: a pathway that can promote cell growth
  • EGFR: a pathway that controls cell growth and is often mutated in cancer
  • FGF/FGF-R: a pathway that controls cell growth, death, and migration
  • HER2: a pathway that controls cell growth and is commonly overexpressed in cancer and  associated with metastasis
  • TROP2: a protein that is commonly overexpressed in cancer and appears to aid  cancer cell self-renewal, proliferation, invasion, and survival
  • VEGF/VEGF-R: a pathway that can promote blood vessel formation in tumors

Cancer vaccines are designed to elicit an immune response against tumor-specific or tumor-associated antigens, encouraging the immune system to attack cancer cells bearing these antigens. Cancer vaccines can be made from a variety of components, including cells, proteins, DNA, viruses, bacteria, and small molecules. Cancer vaccine targets under evaluation in head and neck cancer clinical trials include:

  • CEA: a protein involved in cellular adhesion normally produced only before birth; often abnormally expressed in cancer and may contribute to metastasis
  • HER2: a pathway that controls cell growth and is commonly overexpressed in cancer and associated with metastasis
  • Human Papilloma Virus (HPV)-related antigens: foreign viral proteins expressed by HPV-infected cancer cells
  • MUC-1: a sugar-coated protein that is commonly overexpressed in cancer
  • Personalized neoantigens: these abnormal proteins arise from mutations and are expressed exclusively by tumor cells
  • Ras: a central signaling protein that is commonly mutated in cancer and has been linked to abnormal growth and cell division
  • Telomerase: an enzyme that helps maintain the health of cellular DNA; exploited by cancer cells to achieve immortality
  • Tumor-associated antigens (TAAs): proteins often expressed at abnormally high levels on tumor cells that can be used to target them; also found on normal cells at lower levels
  • WT1: a protein that is often mutated and abnormally expressed in patients with cancer, especially Wilms’ tumor (WT)

Adoptive cell therapy takes a patient’s own immune cells, expands or otherwise modifies them, and then reintroduces them to the patient, where they can seek out and eliminate cancer cells. In CAR T cell therapy, T cells are modified and equipped with chimeric antigen receptors (CARs) that enable superior anti-cancer activity. Natural killer cells (NKs) and tumor infiltrating lymphocytes (TILs) can also be enhanced and reinfused in patients. Cell-based immunotherapy targets under evaluation in head and neck cancer clinical trials include:

  • Epstein-Barr Virus (EBV)-related antigens: foreign viral proteins expressed by EBV-infected cancer cells
  • MAGE antigens: the genes that produce these proteins are normally turned off in adult cells, but can become reactivated in cancer cells, flagging them as abnormal to the immune system

Immunomodulators manipulate the “brakes” and “gas pedals” of the immune system. Checkpoint inhibitors target molecules on immune cells to unleash new or enhance existing immune responses against cancer. Cytokines regulate immune cell maturation, growth, and responsiveness. Adjuvants can stimulate pathways to provide longer protection or produce more antibodies. Immunomodulator targets under evaluation in head and neck cancer clinical trials include:

  • CD40: activating this co-stimulatory pathway can kick-start adaptive immune responses
  • CD137 (also known as 4-1BB): activating this co-stimulatory pathway can help promote the growth, survival, and activity of cancer-fighting T cells
  • CSF1/CSF1R: blocking this pathway can help reprogram cancer-supporting macrophages              
  • CTLA-4: blocking this pathway can help promote expansion and diversification of cancer-fighting T cells
  • ICOS: activating this co-stimulatory pathway on T cells can help enhance immune responses against cancer
  • IDO: blocking this enzyme’s activity can help prevent cancer-fighting T cells from being suppressed
  • IL-2/IL-2R: activating this cytokine pathway can help promote the growth and expansion of cancer-fighting T cells
  • OX40: activating this co-stimulatory pathway can help promote T cell survival after activation
  • PD-1/PD-L1: blocking this pathway can help prevent cancer-fighting T cells from becoming “exhausted,” and can restore the activity of already-exhausted T cells
  • STAT3: activating this intracellular signaling protein can help stimulate adaptive immune responses
  • STING: activating this protein in the DNA-sensing pathway can help stimulate immune responses against threats such as viruses and cancer
  • Toll-like receptors (TLRs): activation of these innate immune receptors can help stimulate vaccine-like responses against tumors

Oncolytic virus therapy uses modified viruses that can infect tumor cells and cause them to self-destruct. This can attract the attention of immune cells to eliminate the main tumor and potentially other tumors throughout the body. Viral platforms under evaluation in head and neck cancer clinical trials include:

  • Adenovirus: a family of common viruses that can cause a wide range of typically mild effects including sore throat, fatigue, and cold-like symptoms
  • Herpes simplex virus: a virus that can cause the formation of sores on the mouth and genitals
  • Measles virus: a highly contagious virus that infects the respiratory tract and can cause measles
  • Reovirus: a family of viruses that can affect the gastrointestinal and respiratory tracts in a range of animal species
  • Vesicular stomatitis virus: a virus that belongs to the same family as the rabies virus; can cause flu-like symptoms in humans
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Sources: ACS Facts and Figures 2018; Atlas of Genetics and Cytogenetics in Oncology and Haematology (DOI: 10.4267/2042/46948); Cancer.net; ClinicalTrials.gov; CRI documents; GLOBOCAN 2018; National Cancer Institute (NCI); National Comprehensive Cancer Network (NCCN) Guidelines

Updated January 2019

*Immunotherapy results may vary from patient to patient. Consult a healthcare professional about your treatment options.

*Immunotherapy results may vary from patient to patient.

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