Oral Cavity (Mouth), Lip, and Oropharyngeal (Throat) Cancer: Staging and Treatment

What is staging for cancer?

Staging is the process of learning how much cancer is in your body and where it is. Tests like endoscopy, PET scan, CT, and MRI may be done to help stage your cancer. Your providers need to know about your cancer and your health so that they can plan the best treatment for you.

Cancer staging looks at the size of the tumor and where it is, and if it has spread to other organs. The staging system for oral cavity, lip, and oropharyngeal cancer is called the “TNM system.” It has three parts:

• T-describes the size/location/extent of the "primary" tumor and which, if any, tissues of the oral cavity, lip, or oropharynx the cancer is in.
• N-describes if the cancer has spread to the lymph nodes.
• M-describes if the cancer has spread to other organs (called metastases).

How are oral cavity, lip, and oropharyngeal cancers staged?

Staging is based on:

• The size of your tumor seen on imaging tests and what is found after surgery (if you have had surgery).
• If your lymph nodes have cancer cells.
• Any evidence of spread to other organs (metastasis).
• HPV status: Oropharyngeal cancers that have Human Papilloma Virus (HPV) DNA in them (p-16 positive) tend to respond to treatments differently than cancers that do not have HPV (p16-negative). For this reason, there are two oropharyngeal staging systems:
  • p16 (HPV)-negative oropharynx cancer stages.
  • p16 (HPV)-positive oropharynx cancer stages.

The staging systems are very complex. Below is a summary of the staging. Talk to your provider about the stage of your cancer.

Oral cavity, Lip, and p16 (HPV)-negative Oropharynx Cancer Staging

Stage 0 (Tis, N0, M0): The cancer is still within the epithelium (the top layer of cells lining the oral cavity and oropharynx) and has not yet grown into deeper layers. It has not spread to nearby lymph nodes (N0) or distant sites (M0). This stage is also known as carcinoma in situ (Tis).

Stage I (T1, N0, M0): The cancer is 2 cm or smaller. It’s not growing into nearby tissues (T1), lymph nodes (N0), or to distant sites (M0).

Stage II (T2, N0, M0): The cancer is 2-4 cm. It’s not growing into nearby tissues (T2), lymph nodes (N0), or to distant sites (M0).

Stage III (T3, N0, M0): The cancer is larger than 4 cm (T3). For cancers of the oropharynx, T3 also includes tumors that are growing into the epiglottis (the base of the tongue). It has not spread to nearby lymph nodes (N0) or to distant sites (M0); OR(T1-T3, N1, M0): The cancer is any size and may have grown into nearby structures if oropharynx cancer(T1-T3) AND has spread to 1 lymph node on the same side as the primary tumor. The cancer has not grown outside of the lymph node and the lymph node is no larger than 3 cm (N1). It has not spread to distant sites (M0).

Stage IVA (T4a, N0 or N1, M0): The cancer is any size and is growing into nearby structures AND either of the following:

• It has not spread to nearby lymph nodes (N0).
• It has spread to 1 lymph node on the same side as the primary tumor, but has not grown outside of the lymph node and the lymph node is no larger than 3 cm (N1).

It has not spread to distant sites (M0); OR(T1-T4a, N2, M0): The cancer is any size and may have grown into nearby structures (T0-T4a). It has not spread to distant organs (M0). It has spread to one of the following:

• One lymph node on the same side as the primary tumor, but it has not grown outside of the lymph node and the lymph node is not larger than 6 cm (N2a) OR
• It has spread to more than 1 lymph node on the same side as the primary tumor, but it has not grown outside any of the lymph nodes and none are larger than 6 cm (N2b) OR
• It has spread to 1 or more lymph nodes either on the opposite side of the primary tumor or on both sides of the neck, but has not grown outside any of the lymph nodes and none are larger than 6 cm (N2c).

Stage IVB (Any T, N3, M0): The cancer is any size and may have grown into nearby soft tissues or structures (Any T) AND any of the following:

• It has spread to 1 lymph node that's larger than 6 cm but has not grown outside of the lymph node (N3a) OR
• It has spread to 1 lymph node that's larger than 3 cm and has clearly grown outside the lymph node (N3b) OR
• It has spread to more than 1 lymph node on the same side, the opposite side, or both sides of the primary cancer with growth outside of the lymph node(s) (N3b) OR
• It has spread to 1 lymph node on the opposite side of the primary cancer that's 3 cm or smaller and has grown outside of the lymph node (N3b).

It has not spread to distant organs (M0); OR (T4b, Any N, M0): The cancer is any size and is growing into nearby structures such as the base of the skull or other bones nearby, or it wraps around the carotid artery. This is known as very advanced local disease (T4b). It may or may not have spread to nearby lymph nodes (Any N). It has not spread to distant organs (M0).

Stage IVC (Any T, Any N, M1): The cancer is any size and may have grown into nearby soft tissues or structures (Any T) AND it may or may not have spread to nearby lymph nodes (Any N). It has spread to distant sites such as the lungs (M1).

p16 (HPV)-Positive Oropharynx Cancer Staging

Stage I (T0-T2, N0 or N1, M0): The cancer is no larger than 4 cm (T0 to T2) AND any of the following:

• It has not spread to nearby lymph nodes (N0) OR
• It has spread to 1 or more lymph nodes on the same side as the primary cancer, and none are larger than 6 cm (N1).
• It has not spread to distant sites (M0).

Stage II (T0-T2, N2, M0): The cancer is no larger than 4 cm (T0 to T2) AND it has spread to 1 or more lymph nodes on the opposite side of the primary cancer or both sides of the neck, and none are larger than 6 cm (N2). It has not spread to distant sites (M0); OR (T3 or T4, N0 or N1, M0): The cancer is larger than 4 cm (T3) OR is growing into the epiglottis (the base of the tongue) (T3) OR is growing into the larynx (voice box), the tongue muscle, or bones such as the medial pterygoid plate, the hard palate, or the jaw (T4) AND any of the following:

• It has not spread to nearby lymph nodes (N0) OR
• It has spread to 1 or more lymph nodes on the same side as the primary cancer, and none are larger than 6 cm (N1).

It has not spread to distant sites (M0).

Stage III (T3 or T4, N2, M0): The cancer is larger than 4 cm (T3) OR is growing into the epiglottis (the base of the tongue) (T3) OR is growing into the larynx (voice box), the tongue muscle, or bones such as the medial pterygoid plate, the hard palate, or the jaw (T4) AND it has spread to 1 or more lymph nodes on the opposite side of the primary cancer or both sides of the neck, and none are larger than 6 cm (N2). It has not spread to distant sites (M0).

Stage IV (Any T, Any N, M1): The cancer is any size and may have grown into nearby structures (Any T) AND it might or might not have spread to nearby lymph nodes (Any N). It has spread to distant sites such as the lungs or bones (M1).

How are oral cavity, lip, and oropharyngeal cancers treated?

Treatment for these cancers depends on many things, like your cancer stage, age, overall health, and testing results. There are steps to take before treatment can begin for any kind of head and neck cancer:

• Multidisciplinary treatment is very important. This means you will have providers from many different specialties involved in your care. Many of these providers will see you before you start cancer treatment during visits called consultations. They will work together and with you to create a plan to treat your cancer.
• If you smoke, quit as soon as possible. Smoking may lessen how well your cancer medications work and can worsen side effects.

Your treatment may include some or all the following:

• Surgery.
• Radiation therapy.
• Chemotherapy.
• Targeted Therapy.
• Immunotherapy.
• Supportive/Palliative treatment.
• Clinical trials.

Surgery

Surgery is often the first treatment used for oral cavity, lip, and oropharyngeal cancers. The type of surgery you have depends on where your tumor is, the stage, and your overall health. Surgery for head and neck cancer can be quite challenging, including the removal of tissue and bone and the use of plastic surgery to rebuild facial features to improve how they work and look. To learn more about the types of surgery you may have, visit Surgery and Staging for Lip and Oral Cancer and Surgical Procedures: Surgery and Staging for Oropharyngeal Cancer. Talk with your care team about surgical options you have, any concerns about your body image and function, what you will need to do to heal after surgery, and any side effects you may have.

Radiation Therapy

Radiation therapy is the use of high-energy x-rays to kill cancer cells. Radiation for oral cavity, lip, and oropharyngeal cancer can be used:

• Alone.
• With chemotherapy at the same time (called chemoradiation).
• Before surgery (called neoadjuvant therapy).
• After surgery (called adjuvant therapy).
• With a targeted therapy medication.
• For palliative treatment (to ease symptoms).
• If the cancer has come back (recurrence).

There are two main types of radiation used to treat oral cavity, lip, and oropharyngeal cancers:

• External radiation therapy: A beam of radiation from outside of the body is directed into the body. It may also be called x-ray therapy, 3D conformal radiation, intensity-modulated radiation therapy (IMRT), cobalt, photon, or proton therapy. When this type of radiation is used, you will likely need to wear a mask that is fitted for you to help you keep still during treatments. This mask can cause anxiety and claustrophobia. Your providers will be able to give you advice to help you with wearing the mask during treatment.
• Internal radiation therapy: A radioactive source is placed inside the body, in or near the tumor. This is called brachytherapy or implant therapy. This type of radiation is often only used when oral cavity, lip, and oropharyngeal cancer has come back.

Because radiation can affect nearby tissues, there are many potential side effects of radiation for head and neck cancers. Talk with your care team about which type of radiation, if any, you will receive and the potential side effects.

Chemotherapy

Chemotherapy is the use of anti-cancer medications to kill cancer cells. It can be used before surgery (neoadjuvant), after surgery (adjuvant), or with or without radiation as the main treatment if surgery is not an option. Chemotherapy medications that may be used are cisplatin, carboplatin, 5-fluorouracil (5-FU), paclitaxel, docetaxel, hydroxyurea, methotrexate, and capecitabine. These medications can cause side effects. Ask your medical oncologist which medications would be best for you and when during treatment you will receive them.

Targeted Therapy

These cancers may be treated with targeted therapies that focus on specific gene mutations or proteins in the tumor. Targeted therapies work by targeting something specific to a cancer cell, which lets the medication kill cancer cells and affecting healthy cells less. Sometimes the “target” is found on a certain type of healthy cell and side effects can happen as a result. An example of a targeted therapy used for this type of cancer is cetuximab.

Immunotherapy

Immunotherapy is the use of a person's own immune system to kill cancer cells. An example of an immunotherapy medication that may be used to treat this type of cancer are pembrolizumab and nivolumab. Your tumor may need to be tested to make sure immunotherapy medications will work for you.

Supportive/Palliative Treatment

Your quality of life is very important during and after treatment for head and neck cancer. Supportive and palliative treatments are used to lessen symptoms or side effects that you may have. Head and neck cancer treatment and the cancer itself can cause:

• Pain: Your care team will help you with medications and other therapies for pain. Radiation, surgery, and a nerve block can help as well.
• Nutrition issues: For some patients, difficulty swallowing, mucositis (sore mouth and throat), loss of taste, or a lack of saliva production may make eating hard or impossible. It is important that you are followed closely by a dietitian to support you in food and supplement choices, and to keep good nutritional status. If needed, a speech and swallowing specialist can test if you can swallow safely without choking or inhaling food. Many patients will need to be fed through a tube placed in their stomach (called a PEG or ‘G' tube). In most cases, this is only temporary (for a short time).
• Changes in Body Image: Social workers and psychologists may be needed to help in dealing with the changes in body image and your role in your family.
• Speech problems: A speech therapist can help you regain as much of your speech as possible, and also give you other ways to communicate.

Clinical Trials

You may be offered a clinical trial as part of your treatment plan. To find out more about current clinical trials, visit the OncoLink Clinical Trials Matching Service.

Making Treatment Decisions

Your care team will make sure you are included in choosing your treatment plan. This can be overwhelming as you may be given a few options to choose from. It feels like an emergency, but you can take a few weeks to meet with different providers and think about your options and what is best for you. This is a personal decision. Friends and family can help you talk through the options and the pros and cons of each, but they cannot make the decision for you. You need to be comfortable with your decision – this will help you move on to the next steps. If you ever have any questions or concerns, be sure to call your team.

You can learn more about head and neck cancers at OncoLink.org.