Mouth and oropharyngeal cancer research | Cancer Research UK
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Mouth and oropharyngeal cancer research

All treatments must be fully researched before they can be adopted as standard treatment for everyone. This is so that we can be sure they work better than the treatments we already use. And so we know that the treatments are safe.

First of all, treatments are developed and tested in laboratories. Only after we know that they are likely to be safe are they tested in people in clinical trials. Cancer Research UK supports a lot of UK laboratory research into cancer and also supports many UK and international clinical trials.

For mouth and oropharyngeal cancer, researchers are looking into


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Why research is important

All potential new treatments have to be fully researched before they can be used as standard treatment for everyone. This is so that

  • We can be sure they work
  • We can be sure they work better than the treatments that are already available
  • They are known to be safe

First of all, treatments are developed and tested in laboratories. For ethical and safety reasons, experimental treatments must be tested in the laboratory before they can be tried in patients. If a treatment described here is said to be at the laboratory stage of research, it is not ready for patients and is not available either within or outside the NHS. Cancer Research UK supports a lot of UK laboratory research into cancer.


Finding a trial

Tests of treatments in patients use clinical trials. Cancer Research UK supports many UK and international clinical trials.

There is information about clinical trials, including the 4 phases of clinical trials in the trials and research section. In that section you can also visit our searchable database of clinical trials for head and neck cancer. If you are interested in a particular trial, you can print it off and take it to your own specialist. If the trial is suitable for you, your doctor will need to refer you to the research team.

Everything covered on this page is the subject of ongoing research. Until studies are completed and new effective treatments are found, these experimental treatments cannot be used as standard therapy for mouth and oropharyngeal cancers.

Here is a video on experiences of taking part in a clinical trial:

View a transcript of the video (Opens in a new window)


Research into causes of mouth and oropharyngeal cancer

The PREGO study which has now closed is looking at changes in genes that may make cancer develop in the head or neck area. Researchers collected samples of cells from people who had different stages of head and neck cancer. They are looking at the genes within the tissues. They hope that this will help them to find out more about what changes in genes may cause head and neck cancer.

A small study is looking at the causes of head and neck cancer. This study which has closed, is supported by Cancer Research UK and is looking to see if a virus called the human papilloma virus causes abnormal cells (pre cancers) and cancers of the head and neck. HPV is a common virus that affects many people and doesn't usually cause major problems. But we know from research that certain types of HPV may cause some head and neck cancers.

The people taking part in this study are having a sample of tissue taken because they may have a cancer of the head and neck. The researchers want to look at these tissue samples to see if they find HPV and the molecules this virus makes.

There is another study looking at samples of cells taken from the mouth. The researchers want to study genetic changes and other changes in cells that can affect the development of mouth and oropharyngeal cancer. They are collecting cells from normal mouth tissue as well as from people who have mouth diseases, including mouth cancer. The study aims to find out which gene changes are important, and how the changes affect the way the immune system responds to cancer. The researchers hope that this may help to develop better treatments in the future.


Preventing mouth and oropharyngeal cancer

Preventing cancer with diet, or particular drugs or vitamins, is called chemoprevention. There is information below about

Diet to prevent cancer

A diet high in fresh fruit and vegetables seems to reduce the risk of mouth cancer. But we need much more detailed information about this. A major study called EPIC (The European Prospective Investigation of Cancer) is going on in the UK and 8 other European countries. It is looking into the links between diet and cancer. The trial started in 1992 and is producing reports on diet and a variety of cancers. This will continue for the next 10 to 20 years.

Some doctors and researchers think that antioxidant vitamins and minerals may help to prevent mouth and oropharyngeal cancer when included in a healthy, balanced diet. Vitamins A, C and E are antioxidants. We don't know for sure whether eating these can help prevent cancer. This is a very difficult thing to prove.

Drugs to prevent mouth cancer

Scientists are always looking at different types of drugs to see if they can help prevent cancer. One example is cyclooxygenase-2 (COX-2) inhibitors. These are a group of drugs that reduce inflammation. One of these drugs is called celecoxib. Scientists are studying the possible benefits of regularly taking celecoxib to see if it can help to stop pre cancerous areas in the mouth from turning into cancers. We don’t know of any patient trials using celecoxib in the UK for head and neck cancer.


Diagnosing mouth cancer

Some studies are looking into new ways of collecting and testing cells from the lining of the mouth that could help to diagnose mouth cancer. Doctors usually take a tissue sample (a biopsy) from the inside of the mouth to diagnose mouth cancer. In one study the doctor takes a sample of cells using a soft small bristle brush. The cells are examined using a computer. In another study, they test the cells using a method called dielectrophoresis.


Research into surgery

The SEND-001 trial is supported by Cancer Research UK. It is comparing two standard surgical treatments for mouth cancer, to see if one approach has a better outcome. Mouth cancer can sometimes spread to the lymph glands in your neck. Some people with early mouth cancer may have very small cancers (secondaries) that have spread to their neck that doctor's can’t see, feel or even read on scans. This trial has now closed and we are waiting for the results.

The LIHNCS trial which has closed to recruitment, is looking at using an iodine dye (Lugol's iodine) during surgery to remove cancer of the mouth or the part of the throat just behind the mouth (oropharynx). The iodine stain can show up any areas of cancer cells or precancerous changes close to the tumour so the surgeon can  remove them. The doctors and researchers hope that this will lower the number of abnormal cells left after surgery for cancer of the mouth and throat. Hopefully this will reduce the chance of the cancer coming back after this type of surgery.

 If surgeons find cancer cells in your neck during surgery, they will remove some of the lymph glands. This is called selective neck dissection or SEND. But surgeons can’t always tell who has hidden secondaries. So they can either do a SEND when your mouth cancer is removed, just in case. Or they can just remove your mouth cancer and operate again in the future if secondaries develop. Surgeons want to find out if one of these approaches is better than the other, so this trial is comparing the 2 types of treatment.

There is a trial comparing surgery with monitoring with PET-CT scans. The trial is for people with squamous cell cancers of the head and neck who are having chemoradiation. After chemoradiation, surgery to remove the lymph glands in the neck is the standard treatment but it can have side effects. This trial has now closed to recruitment and we are waiting for the results.  



Radiotherapy research

Doctors are looking at finding better ways of giving radiotherapy to treat cancers of the mouth and oropharynx. One of these is intensity modulated radiotherapy (IMRT). This is radiotherapy where both the radiotherapy beam and the dose within the beam are shaped to match the tumour shape and thickness.

IMRT gives less radiotherapy to normal tissues compared to standard radiotherapy. Research shows that long term side effects such as  a dry mouth can be milder or less common with IMRT. It has been tested in a UK clinical trial called PARSPORT for head and neck cancers, including mouth cancer. The trial found that IMRT worked as well as conventional radiotherapy. The trial also found that 4 out of 10 (40%) people who had IMRT had a dry mouth after treatment compared with just over 7 out of 10 (70%) who had conventional radiotherapy.

The ArChIMEDEs-Op study which has closed to recruitment, is looking at giving an increased dose of IMRT with standard chemotherapy for oropharyngeal cancer. The people taking part have cancer that is not linked to the human papilloma virus (HPV).

The PATHOS trial is looking at less intensive treatment after surgery for oropharyngeal cancer. The people taking part have cancer that has tested positive to HPV. Part of this trial is comparing standard radiotherapy with lower doses of radiotherapy. Other people in this trial may have radiotherapy on its own or radiotherapy and chemotherapy.

The ARTFORCE trial is comparing standard radiotherapy with high dose radiotherapy for mouth and oropharyngeal cancer that has spread into nearby tissues or lymph glands (locally advanced cancer).

Other research trials are looking at combining radiotherapy with biological therapy. You can find out more about radiotherapy trials for mouth and oropharyngeal cancer on our clinical trials database. If you want to see all the trials, tick the boxes for closed trials and trial results.

Radio sensitising drugs

Doctors know that radiotherapy works best on cells that have a good supply of oxygen. Cancer cells do not always have high levels of oxygen, especially the cells in the centre of a tumour. Research aims to find different ways of increasing the oxygen levels of cancer cells so that radiotherapy can kill more of them. Nimorazole is a drug that mimics the effect of oxygen in tumour cells. This drug is still in trials, but in 2012 the European Medicines Agency (EMA) granted nimorazole orphan status. This means it may be available for the treatment of squamous cell carcinoma of the head and neck for patients having radiotherapy.

The aims of the phase 3 NIMRAD trial are to find out whether giving nimorazole with radiotherapy is better than radiotherapy alone for some head and neck cancers (including oropharyngeal cancer). And to learn more about the side effects of nimorazole.


Chemotherapy research

You may have chemotherapy for mouth and oropharyngeal cancer on its own or in combination with other treatments. Doctors are looking into different combinations of drugs, different doses, and giving treatments in a different order. Some of the chemotherapy drugs used are

The CompARE trial is looking at different treatments for oropharyngeal cancer, including chemotherapy and radiotherapy.

Researchers are also looking at different ways of giving chemotherapy. One way is injecting the drugs directly into the arteries that supply the tumour (called intra arterial chemotherapy). Some studies are looking at giving intra arterial chemotherapy at the same time as radiotherapy.

Another way of giving chemotherapy is by injecting the drugs directly into the tumour. This looks promising for mouth and oropharyngeal cancer. But the side effects include pain and damage to the tissue around the tumour. The side effects can be difficult to cope with. So the researchers are looking at how to improve how they give the treatment to reduce the side effects. This is early research.

You can find out more about chemotherapy trials for mouth and oropharyngeal cancer on our clinical trials database. If you want to see all the trials, tick the boxes for closed trials and trial results.


Biological therapy research

Biological therapies are treatments that act on processes in cells. They can control or destroy cancer cells. There are many different types of biological therapy including

Monoclonal antibodies

Monoclonal antibodies (MABs) can block certain receptors on cancer cells that signal the cancer to grow. Research has shown that a monoclonal antibody called cetuximab (Erbitux) can help people with advanced mouth and oropharyngeal cancer to live longer. Researchers continue to look into a number of different monoclonal antibodies for head and neck cancer, including nivolumab.

One trial is comparing nivolumab with standard chemotherapy drugs for head and neck cancer that has come back or spread to another part of the body.

The De-ESCALaTE HPV trial is looking at the side effects of treatment for throat cancer. It is looking at people who have oropharyngeal cancer and human papilloma virus (HPV). HPV is linked to a number of oropharyngeal cancers. The researchers want to find out if the side effects of treating oropharyngeal cancer with cetuximab and radiotherapy are better for patients than cisplatin and radiotherapy (chemoradiation).

A trial is comparing pembrolizumab and chemotherapy for head and neck cancer that has spread or come back after treatment. The researchers want to find out if pembrolizumab is better than chemotherapy in this situation, and to learn more about the side effects. This trial has now closed and we are waiting for the results.

Cancer growth blockers

There are different types of cancer growth blockers. One type is called tyrosine kinase inhibitors. Tyrosine kinases are proteins within cells that trigger them to grow and divide. Blocking tyrosine kinase stops the cells growing and making more cells. Tyrosine kinase inhibitors (TKIs) being tested for mouth and oropharyngeal cancer include

Iressa is also called ZD 1839 or gefitinib. Doctors hope that it will stop the growth of the cancer cells. Iressa is licensed in the UK for lung cancer. But clinical trials are now going on in the UK for mouth and oropharyngeal cancers that have come back after treatment. The research so far has not shown it to work any better than chemotherapy.

Erlotinib (Tarceva) is another type of TKI being investigated by researchers. Early trials have been combining erlotinib with a monoclonal antibody called bevacizumab. The results found that people could cope well with the side effects. But we need more research to find out how well erlotinib works at treating this type of cancer.

Another type of cancer growth blocker is called buparlisib. It works by blocking the action of a protein called PI3K. It is a PI3K inhibitor. A trial is looking at buparlisib with paclitaxel chemotherapy for head and neck cancer (including mouth cancer) that has come back or spread to another part of the body. The aim of the trial is to see if paclitaxel and buparlisib works better than paclitaxel and a dummy drug (placebo).

Gene therapy

Researchers have used a new type of biological therapy called OncoVEX GM-CSF alongside standard treatment for head and neck cancer that had spread to the lymph nodes. In a small trial, 17 people had treatment with radiotherapy and cisplatin chemotherapy as well as OncoVEX GM-CSF directly into the cancer. OncoVEX treatment uses a type of the cold sore virus that has been genetically changed. It makes a natural substance called GM-CSF that attacks cancer cells. The researchers found that the OncoVEX shrank the cancer or helped to stop it coming back in some people. This is a small study but the cancer responded to the treatment in 14 people. So the researchers plan bigger trials using this treatment.

Trials into gene therapy are still in very early stages. We will need larger trials before we know whether these treatments are any better at treating head and neck cancers than the treatments used now.

Vaccine therapy

Doctors are looking into using a vaccine called Reolysin to help treat advanced head and neck cancer. Reolysin is made from a type of virus called reovirus. Reovirus rarely causes any symptoms, but it can kill cancer cells.

A small trial looked at giving Reolysin at the same time as paclitaxel and carboplatin (PC chemotherapy) in people with advanced cancer. The researchers found that the cancer stayed the same or got smaller in more than half the people with head and neck cancer who had Reolysin and PC chemotherapy. The most serious side effects were a drop in the number of blood cells and low blood pressure.

The REO 18 trial is looking at giving Reolysin with paclitaxel and carboplatin chemotherapy for head and neck cancers. The trial is for people with cancer that has spread to other parts of the body or has got worse despite having other treatment. The aim is to see if having Reolysin helps these people more than having the chemotherapy alone. This trial has now closed and we are waiting for the results.

You can find more information about these trials on the clinical trials database.


Light treatment

A phase 2 study is looking at a type of light treatment with chemotherapy for cancer of the head and neck. Researchers are looking at a new treatment called PC A11 for people with squamous cell head and neck cancer that has come back after treatment. With PC A11 treatment, you have a drug called Amphinex which makes body tissue sensitive to light. You also have a chemotherapy drug called bleomycin. After having these drugs, the doctor directs a laser light onto the surface of the cancer, or through fibres that are put directly into the cancer. The light activates the Amphinex, which in turn helps the bleomycin to get into the cancer cells and kill them. The researchers hope that when you have bleomycin in this way you will only need one dose.

Photodynamic therapy (PDT) is another type of light treatment. Doctors hope that PDT may be useful for treating patients with advanced cancer who are not able to have any more standard treatment. PDT will not be able to cure advanced cancer. But it may help to shrink or slow the growth of the cancer and relieve symptoms. Some early research is also looking into using PDT for pre cancer or early cancer in the mouth.


Oxygen therapy to prevent bone damage

Rarely, radiotherapy to the head and neck area can damage the jaw bone. This damage is called osteoradionecrosis (ORN). The problem develops because the blood supply to the area is reduced. Doctors think that a high pressure oxygen therapy called hyperbaric oxygen (HBO) may be able to stop this happening. The idea is that HBO works by increasing the supply of blood to the jaw. 

The HOPON trial is looking at HBO for osteoradionecrosis. You may be able to join this trial if your cancer has been successfully treated with radiotherapy and you are going to have jaw or dental surgery. Doctors think that having dental surgery can trigger the problem.

If you do develop osteoradionecrosis after radiotherapy, your doctor may suggest surgery to remove the damaged jaw bone. HBO may help the bone to heal after surgery. Doctors want to test this in the DAHANCA 21 trial. Half the people taking part will have HBO before and after surgery to remove the bone. The other half will have surgery only.


Research into reducing treatment side effects

Treatment for head and neck cancer can sometimes cause side effects that are difficult to cope with. There is information below about research into

Helping to relieve a dry mouth

One of the main side effects of radiotherapy to the head and neck area is a dry mouth. Doctors call this xerostomia. It happens because radiotherapy affects the glands that make saliva (spit) to keep your mouth moist. You may make less saliva than usual, or none at all.

A dry mouth is very uncomfortable and can make chewing, swallowing and even talking difficult. It can lead to serious weight loss problems. There is a need for new treatments because current treatments are limited. If you are making some saliva, a drug to stimulate your salivary glands may help. These include the drugs pilocarpine and bethanechol. But in about 1 in every 6 patients (15%) these drugs cause unbearable side effects such as blurred vision, sickness, and sweating.

Recent research suggests that a drug called amifostine can help to prevent a dry mouth. This drug is a chemoprotectant, meaning it helps to protect against the harmful side effects of chemotherapy and radiotherapy. A few minutes before each radiotherapy treatment, you have an amifostine injection into a vein in your arm. It works by collecting in the salivary glands and limiting the amount of damage that radiation can cause to the salivary glands. Side effects of amifostine include low blood pressure, dizziness, flushing, chills, and feeling or being sick. This drug is still only being tested at the moment and is not used as standard treatment.

The LEONIDAS-2 study is looking at a medical device to stimulate the gums to increase the amount of saliva in the mouth. The researchers hope this will reduce the symptoms of dry mouth and improve quality of life. This study is closed and we are waiting for the results.

Some studies suggest that having acupuncture can help with a dry mouth caused by radiotherapy in people with head and neck cancers. But we need more research before we will know exactly how much it can help.

Our section about mouth problems with cancer has detailed information about treatments for a dry mouth.

Helping people with mouth opening problems (trismus)

Some people find it difficult to open their mouth properly after radiotherapy for mouth or oropharyngeal cancer. This is because radiotherapy can affect the muscles that you use to open and close your mouth. It is called trismus.

Trismus can be treated by gently stretching the jaw muscles using wooden spatulas. The Trismus trial is comparing this with the Therabite device. This is a hand operated device you put inside your mouth. The aim of the trial is to see which is best to treat trismus, which improves quality of life the most and which exercise routine people stick to best. This trial has now closed and we are waiting for the results.

Acupuncture for pain after a neck dissection

Some people who have a neck dissection operation to remove lymph nodes in their neck also have their accessory nerve removed. This nerve controls shoulder movement, and the surgery can leave your shoulder and neck stiff and painful. These side effects are usually treated with physiotherapy and non steroidal anti inflammatory pain killers (NSAIDs). Early research in USA suggests that acupuncture may also help to relieve the pain caused by having a neck dissection.

Acupuncture and moxibustion to help relieve lymphoedema

Lymphoedema is swelling caused by a build up of lymph fluid in the body. It can be a side effect of surgery or radiotherapy treatment if the lymph nodes that usually drain the fluid are removed or damaged. Lymphoedema can cause discomfort, pain and difficulty moving. There is no cure for lymphoedema, but treatments can relieve symptoms.

A small trial looked at acupuncture and moxibustion for lymphoedema. These are types of complementary therapies. Acupuncture uses fine sterile needles which are put just under the skin at particular points (acupuncture points) on the body. In this trial, they did not put the acupuncture needles in the area affected by lymphoedema. Moxibustion uses a dried herb called mugwort which is rolled into a stick. The moxibustion practitioner holds the glowing end of the lit stick over acupuncture points to warm them.

The trial team found that acupuncture and moxibustion was safe for people with lymphoedema, especially when the needles are not put in the area of lymphoedema. The people taking part reported some improvement in their symptoms. The team suggest that more research is needed to see how much it could help improve symptoms.

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Updated: 21 October 2014