Immunotherapies to Treat Head and Neck Cancer

In the United States, some 54,010 people were expected to have a diagnosis of head and neck cancers in 2021, and nearly 11,000 people would die from it. More than 70% of these cancers of the mouth, throat, and other nearby structures will happen in men. One major problem involves treating people with metastatic head and neck cancer, as the chance of survival is generally poor.

The good news is that research moves forward quickly, and healthcare providers now use immunotherapies in treating some of these cancers. Immunotherapy appears safe, improves symptoms, and may even extend survival time for some people.

This article explains the types of head and neck cancer, and some of the possible causes. It then looks at what immunotherapy drugs are, and which ones are approved for treating these cancers.

Doctor holding vial and syringe
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Overview of Head and Neck Cancer

First, it's good to get an idea of how head and neck cancers affect people. It will help you to see how the immunotherapy drugs work.

What Is a Squamous Cell?

Most head and neck cancers arise from squamous cells. They are skinny, flat cells that line the surface of the skin, the digestive and respiratory tracts, and certain organs in the body.

Examples of areas where squamous cell carcinoma, or cancer, can develop include these sites:

  • Mouth
  • Lung
  • Skin
  • Cervix
  • Vagina
  • Anus

What Does Malignant Mean?

A malignant tumor in the head and neck region means that these cancer cells are growing uncontrollably. They may or may not have invaded normal healthy tissue, depending on the stage of the cancer.

Radiation and chemotherapy often are used to treat malignant and potentially fatal tumors. The new immunotherapy drugs also are used to treat these cancers in certain patients.

Where Is Head and Neck Cancer Located?

The term "head and neck" may seem vague because there are more than one possible sites for cancer. It's important to know exactly where this type of cancer is when it is diagnosed.

Head and neck cancer refers to tumors that start in one of these many areas:

  • Lip/mouth
  • Back of the mouth or throat (the oropharynx)
  • Lower part of the throat, behind and near the voice box (the hypopharynx)
  • Upper part of the throat behind the nose (the nasopharynx)
  • Voice box (called the larynx)

The symptoms of these cancers vary, depending on the affected location. They may include sores in the mouth or tongue, growing trouble with swallowing food, or a new hoarseness in your voice.

What Causes Head and Neck Cancer?

In the past, head and neck cancer always was linked to tobacco and alcohol use. Globally, about 75% of them still are.More recently, some head and neck cancers are linked with certain strains of human papillomavirus (HPV). About 10% of men and 3.6% of women have oral HPV infections.

Infection with HPV is extremely common, yet only a small percentage of people develop cancer from it. This is because most people's immune systems clear the infection. But a strain of HPV called HPV-16, which causes cervical cancer and anal cancer in men and women, is linked with cancer of the oropharynx. HPV is thought to cause 70% of oropharyngeal cancers.

Healthcare providers and researchers have seen a rise in the head and neck cancers attributed to HPV. At the same time, the cases linked to tobacco and alcohol are decreasing. Experts think that it could be due to a societal change in sexual behavior, as oral sex is now more common in some cultures.

The increasing numbers are driving interest in how to best treat HPV-positive head and neck cancers, which differ from other head and neck tumors. Among the treatment choices are immunotherapy drugs.

What Are Immune System Checkpoints?

Immune system checkpoints are proteins normally located on a person's immune system cells. These are called T cells. The T cells are like guardians at watch, always looking for infection and cancer in the body.

When a T cell meets another cell, it "reads" proteins on the surface to identify the cell and know if it is "normal" or not. If not, the T cell will begin to attack the cell. But during this attack, how are normal, healthy cells protected?

This is where checkpoint proteins come into play. These proteins stay on the surface of T cells to ensure that healthy cells are left alone. Cancer cells, though, upend the system by making the checkpoint proteins themselves in order to avoid attack. One such protein is called PD-1.

Scientists discovered that they can block PD-1 on cancer cells, so that the cancer is "seen" and therefore attacked by a person's immune system. This is where immunotherapy comes into play, with PD-1 blocking drugs that are called immune system checkpoint inhibitors.

Recap

People who have cancers of the mouth, throat, and nose are said to have head and neck cancers. These cancers are often linked to alcohol and tobacco use, or to HPV infection. They may be treated with relatively new immunotherapy drugs. These drugs are PD-1 blockers, meaning they boost the body's own immune system to help fight cancer.

Immunotherapy Treatment

By 2021, there were three immune system checkpoint inhibitors approved by the U.S. Food and Drug Administration (FDA). They are approved for head and neck squamous cell carcinoma in cases where the cancer has spread, and in situations where chemotherapy treatments have not worked.

These immunotherapies are called:

  • Keytruda (pembrolizumab)
  • Opdivo (nivolumab)
  • Jemperli (dostarlimab-gxly)

Keytruda

Studies showed this drug has a good safety profile and can work to shrink some people's cancer. In one drug trial, 171 people with head and neck cancer got Keytruda infusions every three weeks. Their cancer had advanced despite previous chemotherapy and the use of Erbitux (cetuximab), a fourth drug for head and neck cancer that is a monoclonal antibody therapy.

The cancers shrank or disappeared in 16% of the cases, and the average length of time it kept working was about 8 months. In terms of safety, two-thirds of participants reported side effects but only 15% had any severe impacts.

The most common side effects were:

  • Fatigue
  • Hypothyroidism (an underactive thyroid gland)
  • Nausea
  • Elevation of a liver enzyme
  • Diarrhea

Overall, the only immune system-related effects were high and low thyroid levels, and pneumonitis.

Immunotherapy drugs work in careful balance with the body. They protect healthy tissue and destroy cancer cells. But side effects are a big concern because the drugs may prompt the immune system to attack healthy cells too.

Opdivo

Another drug trial included more than 350 people with head and neck cancer. Their disease had progressed despite platinum-based chemotherapy, and they were given either Opdivo every two weeks, or a standard therapy of one of three other drugs, including Erbitux.

The results showed a longer overall survival time in the people who received Opdivo. Their median survival times was 7.5 months, compared with 5.1 months for the standard therapy group. The one-year survival rate was 36% in the Opdivo group versus 16.6%.

In other words, the one-year survival rate more than doubled. Some people had serious side effects, but it was just 13% in the Opdivo group versus 35% of the standard therapy group. The Opdivo group also saw fewer quality of life impacts when compared with chemotherapy.

Jemperli

The FDA initially approved this immunotherapy drug in April 2021, and then expanded its approval in August 2021. It also is a checkpoint inhibitor and PD-1 blocker. It may be used only in some people with advanced head and neck cancer.

These people have a DNA mismatch repair deficiency (MMR) or have not responded to other treatments. The cells in someone who has an MMR are more likely to have mutations, or changes, that they are unable to repair. This is often linked to cancer.

Jemperli continues to be studied for uses in other cancers, including lung cancer.

Summary

Immunotherapy drugs are already changing the face of cancer treatment. There are three drugs that can be used to treat some people with head and neck cancers.

There is much more research to be done, but these drugs show promise in reducing symptoms, improving quality of life, and extending survival time for people with these cancers.

A Word From Verywell

Remember that treating head and neck cancer is a complex process. There are many factors that go into deciding exactly how your healthcare provider wants to treat your particular case. These drugs aren't for everyone, and decisions will depend on your medical history, the other drugs you've tried already, and any side effects. Remain an advocate for your own cancer health by gaining knowledge. The journey is long and arduous, but try to seek out comforts and joys along the way too.

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4 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021CA A Cancer J Clin. 2021;71(1):7-33. doi: 10.3322/caac.21654

  2. Marziliano A, Teckie S, Diefenbach MA. Alcohol‐related head and neck cancer: Summary of the literatureHead & Neck. 2020;42(4):732-738. doi: 10.1002/hed.26023

  3. Centers for Disease Control and Prevention. HPV and Oropharyngeal Cancer. Updated September 3, 2020.

  4. Food and Drug Administration. Drug Approval Package: Jemperli. August 17, 2021.

Additional Reading
  • Bauml J et al. Pembrolizumab for platinum- and cetuximab-refractory head and neck cancer: Results from a single-arm, phase II study. J Clin Oncol. 2017 May 10;35(14):1542-49.
  • Brockstein BE, Vokes E. Treatment of metastatic and recurrent head and neck cancer. In:UpToDate, Posner MR (Ed), UpToDate, Waltham, MA.
  • Economopoulou P, Perisanidis C, Giotakis EI, Psyrri A. The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications. Ann Transl Med. 2016 May;4(9):173.
  • Ferris RL et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016 Nov 10;375(19):1856-67.
  • National Cancer Institute. (2017). Head and Neck Cancer. Health Professional Version: Research.