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Oral Cancers: NCCN Guidelines for Patients

December 23, 2022 - read ≈ 11 min



The NCCN Guidelines for Patients were developed by the National Comprehensive Cancer Network (NCCN). NCCN is an organization that unites leading cancer care centers in the United States of America. Its activities are focused on scientific research, treatment and education of patients.

Oral cancer basics

You’ve learned that you have oral cancer. It’s common to feel shocked and confused. This chapter reviews some basics that may help you learn about oral cancer.

Lips and mouth

Before learning about oral cancers, it is helpful to know about the lips and mouth. These parts of the body are needed for talking and eating. The lips keep food in the mouth and help to pronounce words.

The mouth starts to break down food for the body to digest. It also helps you say words.


The outer (or dry) lips are like your skin. So, cancers of the outer lips are treated as skin cancers. These cancers are not covered in this book.

The inner (or wet) lips are like the insides of your cheeks. (See Figure 1). Cancers of the inner lips are treated as oral cancers. Treatment for these cancers is covered in this book.

Figure 1. Lips and mouth.
Oral cancers occur in the inner lips, the anterior tongue, inner cheeks, roof of the mouth, floor of the mouth (not shown), and gums.


Oral cancers include cancers of the mouth. They do not include bone cancers of the jaw. Oral cancers often occur in these parts of the mouth:

  • The buccal mucosa is the inside of the cheeks.
  • The floor of the mouth is under your tongue between your teeth.
  • The anterior tongue is the first two-thirds of your tongue.
  • The alveolar ridge is the gums around the base of your teeth.
  • The retromolar trigone is the gums behind your wisdom teeth.
  • The hard palate is the roof of your mouth.

Lymph nodes

Throughout your body — including your mouth—is a clear fluid called lymph. Lymph gives cells food and water. It also contains germ-fighting blood cells. Lymph drains from tissue into vessels that transport it to the bloodstream. (See Figure 2). As lymph travels, it passes through small structures called lymph nodes. Lymph nodes remove germs from lymph.

I still have challenges as a result of the treatments, but every day that I have to endure these reminders is another day that I get to appreciate still being here, experiencing the joy of being with my family.

— Tony, 10-year cancer survivor Stage IV tongue and tonsil cancer
Figure 2. Lymph nodes. 
Throughout your body is a clear fluid called lymph. It drains from tissues into vessels that carry it back to the bloodstream. As lymph travels, it passes through lymph nodes. Lymph nodes remove germs from lymph. Lymph vessels and nodes are depicted in green in the figure.

A disease of cells

Your body is made of trillions of cells. Cancer is a disease of cells. Each type of cancer is named after the cells from which it formed.

Almost all oral cancers are carcinomas. Carcinomas are cancers of cells that line the inner or outer surfaces of the body. There is more than one type of oral carcinoma. The most common type is squamous cell carcinoma. Squamous cells cover the lips and other areas of the mouth.


Cells have a control center called the nucleus. Within the nucleus are chromosomes. Chromosomes are long strands of DNA (deoxyribonucleic acid) that are tightly wrapped around proteins. (See Figure 3). Within DNA are coded instructions for building new cells and controlling how cells behave. These instructions are called genes.

Figure 3. Genetic material in cells.
Most human cells contain a plan called the “blueprint of life.” It is a plan for how our bodies are made and work. It is found inside of chromosomes. Chromosomes are long strands of DNA that are tightly wrapped around proteins. Genes are small pieces of DNA. Humans have about 20,000 to 25,000 genes.

There can be abnormal changes in genes called mutations. Some types of mutations that are linked to cancer are present in all cells. Other mutations are present only in cancer cells. Mutations cause cancer cells to behave unlike normal cells. They sometimes cause cancer cells to look very different from normal cells.

Cancer’s threat

When needed, normal cells grow and then divide to form new cells. When old or damaged, they die as shown in Figure 4. Normal cells also stay in place. Cancer cells don’t behave like normal cells. Cancer cells differ from normal cells in three key ways.

Figure 4. Normal cells vs. cancer cells.
Normal cells increase in number when they are needed and
die when old or damaged. In contrast, cancer cells quickly make new cells and live longer because of mutations in genes.

Mass of cells

Cancer cells make new cells that aren’t needed. They don’t die quickly when old or damaged. Over time, cancer cells form a mass called the primary tumor.


Cancer cells can grow into surrounding tissues. If not treated, the primary tumor can grow beyond the surface of the mouth into deeper tissue. Examples include growth into the jawbone, skin, or sinuses. Invasion can cause pain. It can also make it hard to talk, chew, or taste.


Third, unlike normal cells, cancer cells can leave the lips and mouth. This process is called metastasis.

In this process, cancer cells break away from the tumor and merge with blood or lymph. Then, the cancer cells travel through blood or lymph vessels to other sites. Once in other sites, cancer cells may form secondary tumors. Over time, major health problems can occur.

Cancer stages

A cancer stage is a rating of the cancer based on test results. Your doctor uses it for many things. It is used to assess the outlook of the cancer (prognosis). It is used to plan treatment. It is also used for research.

Cancer staging is often done twice. The rating before any treatment is called the clinical stage. The rating after surgery is called the pathologic stage.

Staging system

The AJCC (American Joint Committee on Cancer) staging system is used to stage oral cancer. In this system, the letters T, N, and M describe the extent of the cancer.

T score

The T score describes the growth of the primary tumor. There are 6 main scores. TX means the primary tumor could not be found. Tis means the tumor is only within the top layer of tissue. T1 through T3 describe the size of the tumor. T4 is based on either size or growth into nearby structures. The more serious the growth the higher the T score.

N score

The N score describes the cancer status of nearby lymph nodes. There are 5 main scores. NX means the nodes could not be assessed. N0 means the nodes are cancer-free. N1 through N3 is based on

  1. number of nodes with cancer;
  2. cancer on one or both sides of the neck;
  3. nodal size;
  4. cancer growth through the outer wall of the node.

The more serious the growth the higher the N score.

M score

The M score tells if the cancer has spread to body parts distant from the mouth and neck. M0 means there are no distant metastases. M1 means one or more distant metastases are present. The lungs are the most common place to which oral cancers spread. They also can spread to the bone and liver.

Numbered stages

The TNM scores are combined to assign the cancer a stage. The stages range from stage 0 to stage 4. Stage 4 is further grouped by the letters A through C. Doctors write these stages as — stage 0, stage I, stage II, stage III, stage IVA, stage IVB, and stage IVC.

If the cancer recurs or worsens, the stage stays the same. An example is a stage III cancer that recurs with metastatic disease. It is not now stage IVC. It remains stage III.

The numbered stages are very alike across cancers, but the outcomes differ. For oral cancer, many stages including IVA and IVB are treated with the goal of curing it. For stage IVC, the goal of treatment is to control the growth of the cancer.

Treatment types

This section briefly describes the treatments used for oral cancers. Not everyone receives the same treatment. Your doctor will tailor treatment to you based on tests described in Part 2. Treatment options based on the cancer stage are discussed in Parts 3 through 5.

Local therapy

Local therapy treats cancer in a limited region. It cannot fully treat cancer that is widespread. Local therapies for oral cancers include surgery and radiation therapy.


Surgery is a treatment that removes tumors or entire organs with cancer. It is a very common treatment for oral cancers.

The method used depends on where and how much the cancer has grown. Most often, surgeons remove oral cancers through a cut into tissues. The cutting device may be a scalpel, cautery device, or laser beam.

Some small oral cancers may be removed through the open mouth. Lasers or a machine (“robot”) may be used to remove the cancer. A surgeon with the proper training and experience should perform these methods.

Radiation therapy

Radiation therapy most often uses high-energy x-rays to treat oral cancer. The x-rays damage DNA in cancer cells. This either kills the cancer cells or stops new cancer cells from being made.

For oral cancers, the most common radiation method is EBRT (external beam radiation therapy). A large machine makes the high energy x-rays used for treatment. Conformal techniques are used. These techniques shape the radiation dose to the cancer site to spare healthy tissue. NCCN experts recommend the following techniques:

  • 3D-CRT (three-dimensional conformal radiation therapy) delivers an x-ray beam that matches the shape of the target.
  • IMRT (intensity-modulated radiation therapy) better spares normal tissue during treatment by modifying the beam’s intensity.

Systemic therapy

Systemic therapy is a cancer treatment for the whole body. It will treat the cancer in your mouth or lips. It will also treat cancer in lymph nodes and distant parts of your body.

For oral cancers, systemic therapy consists of cancers drugs. Many of these drugs are liquids that are slowly injected into the body. Some drugs are pills to be swallowed.


Chemotherapy works by stopping the cell life cycle. As a result, cancer cells cannot make new cells. Chemotherapy can also cause cells to destroy themselves. Cisplatin is a commonly used chemotherapy drug for oral cancers. It is sometimes used with radiation therapy to treat oral cancers.

Targeted therapy

For oral cancers, targeted therapy stops growth signals from a structure on cancer cells called EGFR (epidermal growth factor receptor). The drug, cetuximab, stops EGFR signals and allows immune cells to destroy cancer cells. It is commonly used with radiation therapy to treat oral cancers.

Afatinib may also help treat oral cancers by stopping EGFR signals. However, more research is needed.


T cells are a type of immune cell that can kill cancer cells. They are unable to attack cancer cells that have a protein called PD-L1. Pembrolizumab and nivolumab block PD-L1 and allow T cells to attack cancer cells.

Clinical trials

One of your treatment options may be to join a clinical trial. Joining a clinical trial is strongly supported. NCCN believes that you will receive the best management in a clinical trial.

A clinical trial is a type of research that studies a test or treatment in people. It gives people access to health care that otherwise can’t usually be received. Ask your treatment team if there is an open clinical trial that you can join.


  • Oral cancers include cancers of the inner lips and mouth.
  • The most common type of oral cancer is squamous cell carcinoma. Squamous cells cover the lips and other areas of the mouth.
  • Cancer cells form a tumor since they don’t grow and die as normal cells do.
  • Oral cancers can spread through lymph or blood to other body parts.
  • Most oral cancers are treated with surgery. But, you may get other treatments like radiation or chemotherapy.
  • Clinical trials give people access to new tests and treatments that they otherwise wouldn’t receive.

You can read more about Oral Cancers, its treatment methods and follow-up after treatment in the full text of the recommendations for patients by downloading it below.

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