Head & Neck

Throat Cancer

Includes illustrated staging details

The throat is the more common name for the pharynx (FAYR-inx), a muscular, hollow tube about five inches long. As part of both the respiratory and the digestive systems, it functions as a passageway for air, food and liquid. It begins at the back of the nasal cavity and curves down to meet the esophagus and trachea (windpipe). It is divided into three parts: the nasopharynx, the oropharynx (which includes tonsils) and the hypopharynx.

Throat cancer typically begins in the thin, flat squamous (SKWAY-mus) cells lining the mucous membranes. It may be more specifically referred to by the affected region: nasopharyngeal cancer, oropharyngeal cancer or hypopharyngeal cancer.

Although the oropharynx is at the back of the mouth, oropharyngeal cancer is diagnosed as a throat cancer because the oropharynx is part of the throat. The human papillomavirus (HPV) is linked to most oropharyngeal cancers (see HPV and Cancer, page 11). Nasopharyngeal cancer may be caused by the Epstein-Barr virus (EBV), particularly in people of Asian descent. Also known as human herpesvirus 4, EBV is among the most common human viruses.

Treatment Options

To develop a treatment plan tailored to you and the type of cancer you have, your doctor will consider the region of the throat where the cancer occurs, whether the cancer is primary or recurrent, and the presence of certain biomarkers related to HPV. Ask your doctor if your diagnosis is HPV+ or HPV-. You will need to look carefully at the staging table headlines in this guide to ensure you view the information that applies to your diagnosis as they are staged differently.

Preserving normal function as much as possible will be a priority. Your doctor may suggest one or more of the following options.

Surgery is commonly used to treat oropharyngeal and hypopharyngeal cancers. It is rarely used for nasopharyngeal cancers because the area can be difficult to reach. However, it may be used for nasopharyngeal cancer that does not respond to radiation therapy and to remove lymph nodes or other tissues in the neck. One or more of the following surgeries may be used.

Transoral robotic surgery (TORS) is an option for early-stage oropharyngeal cancers (especially HPV+ tumors). It can be used to remove cancers from the tonsils or the back one-third of the tongue, called the base of tongue. TORS may also be used to treat select, small hypopharyngeal cancers.

Radical tonsillectomy, also known as lateral oropharyngectomy, removes the tonsil as well as a cuff of tissue around the tonsil, including part of the soft palate, pharynx and base of tongue.

Base of tongue resection removes the tumor from the back one-third of the tongue.

Partial pharyngectomy removes part of the pharynx (throat).

Laryngopharyngectomy removes tumors in the hypopharynx. This involves the removal of the larynx (voice box), the vocal folds and pharynx. With this approach, a surgeon reconstructs the pharynx and the surgeon creates a stoma for breathing. Laryngopharyngectomy is typically reserved for large tumors or those that fail nonsurgical treatment.

A neck dissection to remove lymph nodes may be performed.

Reconstructive surgery may be recommended to restore function or appearance and replace missing tissue. This surgery would take place at the same time the cancer is being removed.

Radiation therapy may be given alone or with chemotherapy (chemoradiation) as a first-line treatment for throat cancers in which surgery is not a good option.

External-beam radiation therapy (EBRT) is the most common type of radiation therapy used to treat throat cancers. It includes intensity-modulated radiation therapy (IMRT), stereotactic radiation therapy and proton therapy, with IMRT being the most commonly used and well-researched.

Hyperfractionated radiation therapy, in which the radiation is given in smaller doses but more frequently, may be used for certain cases of advanced throat cancer to improve the way the tumor responds to treatment.

Brachytherapy is a type of internal radiation therapy that may be used in some cases. It surgically implants tiny pellets or rods containing radioactive material in or near the cancer for several days. They are then removed.

Radiation with or without chemotherapy may be recommended following surgery as adjuvant treatment for advanced stage cancers. This therapy may be used to eliminate any remaining cancer cells and to lower the risk of recurrence.

Drug therapy may be used alone or in combination with other therapies.

Chemotherapy given alone may be used to treat cancer that has returned (recurrent) or cancers that are not surgically resectable. In this case, the goal of treatment may be to prevent growth and spread as opposed to cure. It may be given after surgery as adjuvant therapy with radiation therapy (chemoradiation) if the risk for recurrence is high. For nasopharyngeal cancers, additional chemotherapy may be given before starting chemoradiation treatment, also called neoadjuvant chemotherapy. Chemoradiation may be an option for the first treatment used.

Immunotherapy in the form of immune checkpoint inhibitors may be an option for treating certain recurrent or metastatic throat cancers. The doctor will test for the tumor’s PD-L1 expression, which may indicate whether the tumor could respond to immunotherapy. If expression is more than 1 percent, the tumor is considered to be PD-L1 positive and immunotherapy alone may be used. If PD-L1 is negative, immunotherapy and traditional chemotherapy are often combined for patients who have recurrent/metastatic cancer.

Targeted therapy drugs may be an option to treat types of throat cancer that contain specific genetic abnormalities, proteins or growth factors. Epidermal growth factor receptor (EFGR) inhibitors are approved for oropharyngeal and hypopharyngeal cancer in combination with radiation therapy or chemotherapy.

Staging

Diagnosing your type of throat cancer is an important step in creating the best treatment plan for you. Your doctor will perform a thorough exam, imaging studies, blood tests and a biopsy and use these test results to stage the cancer. Staging determines the extent of your cancer, where it is located and whether it has metastasized (spread) to nearby organs, tissues or lymph nodes, or to other parts of your body.

The TNM staging system, developed by the American Joint Committee on Cancer (AJCC), is typically used to classify and stage throat cancer. This system classifies the cancer by tumor (T), node (N) and metastasis (M). The T category describes the size and location of the primary tumor. The N category indicates whether the lymph nodes show evidence of cancer cells. The number and location of these lymph nodes are important because they show how far the disease has spread. The M category describes metastasis (spread of cancer to another part of the body), if any.

Staging Criteria

Once the cancer is classified, an overall stage is assigned. Throat cancer may be Stage 0 through Stage IV. Also known as “in situ,” Stage 0 is a precursor of an invasive cancer. Stages I and II are generally confined to the local area where the cancer is found, and Stage III has spread to the regional lymph nodes in the neck. Stage IV is further divided into Stages IVA, IVB and IVC. Stages IVA and IVB are locally or regionally advanced disease, and Stage IVC has spread to distant sites, such as the liver, lungs or bone.

These basic stages are designed to group patients who have a similar prognosis (outlook). This grouping allows doctors to more accurately predict outcomes for patients depending on the type of treatment they receive. In certain cancers, the stage is also determined by other factors. For throat cancer, the presence of human papillomavirus (HPV) and the location of the cancer cells are considered..

Sometimes your doctor may reassess your stage after treatment or if cancer recurs. This is known as restaging. It is rarely done but typically involves the same diagnostic tests used for the original staging. If a new stage is assigned, it’s often preceded by an “r” to denote that it’s been restaged and different from the original stage given at diagnosis.

Look carefully at the table headlines and sections to ensure you view the information that applies to your diagnosis as each has unique staging characteristics.

TNM Classification for Oropharyngeal (HPV-) and Hypopharyngeal Cancers

Classification Definition
Tumor (T)
TX Primary tumor cannot be assessed.
Tis Carcinoma in situ.
Oropharyngeal (HPV-)
T1 Tumor 2 cm or smaller in greatest dimension.
T2 Tumor larger than 2 cm but not larger than 4 cm in greatest dimension.
T3 Tumor larger than 4 cm in greatest dimension or extension to lingual surface of epiglottis.
T4 Moderately advanced or very advanced local disease.
  T4a Moderately advanced local disease. Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate or mandible (jawbone).
  T4b Very advanced local disease. Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base or encases carotid artery.
Hypopharyngeal
T1 Tumor limited to one subsite of hypopharynx and/or 2 cm or smaller in greatest dimension.
T2 Tumor invades more than one subsite of hypopharynx or an adjacent site, or measures larger than 2 cm but not larger than 4 cm in greatest dimension without fixation of hemilarynx.
T3 Tumor larger than 4 cm in greatest dimension or with fixation of hemilarynx or extension to esophageal mucosa.
T4 Moderately advanced and very advanced local disease.
  T4a Moderately advanced local disease. Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, esophageal muscle or central compartment soft tissue.
  T4b Very advanced local disease. Tumor invades prevertebral fascia, encases carotid artery or involves mediastinal structures.
Node (N)
NX Regional lymph nodes cannot be assessed.
N0 No regional lymph node metastasis.
N1 Metastasis in a single ipsilateral (on the same side) lymph node 3 cm or smaller in greatest dimension and ENE*(-).
N2 Metastasis in a single ipsilateral (on the same side) lymph node 3 cm or smaller in greatest dimension and ENE*(+);
or larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-);
or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-);
or in bilateral (on both sides) or contralateral (on the opposite side) lymph node(s), none larger than 6 cm in greatest dimension and ENE(-).
  N2a Metastasis in single ipsilateral (on the same side) node 3 cm or smaller in greatest dimension and ENE*(+);
or a single ipsilateral node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-).
  N2b Metastasis in multiple ipsilateral (on the same side) nodes none larger than 6 cm in greatest dimension and ENE*(-).
  N2c Metastasis in bilateral (on both sides) or contralateral (on the opposite side) lymph node(s), none larger than 6 cm in greatest dimension and ENE*(-).
N3 Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE*(-);
or metastasis in a single ipsilateral (on the same side) node larger than 3 cm in greatest dimension and ENE*(+);
or multiple ipsilateral, contralateral (on the opposite side) or bilateral (on both sides) nodes, any with ENE(+);
or a single contralateral node of any size and ENE(+).
  N3a Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE*(-).
  N3b Metastasis in a single ipsilateral (on the same side) node larger than 3 cm in greatest dimension and ENE*(+);
or multiple ipsilateral, contralateral (on the opposite side) or bilateral (on both sides) nodes, any with ENE(+);
or a single contralateral node of any size and ENE(+).
Metastasis (M)
M0 No distant metastasis.
M1 Distant metastasis.

*Extranodal extension (ENE) refers to cancer cells that have spread beyond the lymph node into surrounding tissues.

Staging Oropharyngeal (HPV-) and Hypopharyngeal Cancers

Stage T N M
0 Tis N0 M0
I T1 N0 M0
II T2 N0 M0
III T3
T1, T2, T3
N0
N1
M0
M0
IVA T4a
T1, T2, T3, T4a
N0, N1
N2
M0
M0
IVB Any T
T4b
N3
Any N
M0
M0
IVC Any T Any N M1

Illustrated Stages of Oropharyngeal (HPV-) Cancer






Illustrated Stages of Hypopharyngeal Cancer







Classifying & Staging Oropharyngeal (HPV+) Cancer

Classification Definition
Tumor (T)
T0 No primary identified.
T1 Tumor 2 cm or smaller in greatest dimension.
T2 Tumor larger than 2 cm but not larger than 4 cm in greatest dimension.
T3 Tumor larger than 4 cm in greatest dimension or extension to lingual surface of epiglottis.
T4 Moderately advanced local disease. Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate or mandible (jawbone) or beyond.
Node (N)
NX Regional lymph nodes cannot be assessed.
N0 No regional lymph node metastasis.
N1 Metastasis in four or fewer lymph nodes.
N2 Metastasis in more than four lymph nodes.
Metastasis (M)
M0 No distant metastasis.
M1 Distant metastasis.
Stage T N M
I T0, T1, T2 N0, N1 M0
II T0, T1, T2
T3, T4
N2
N0, N1
M0
M0
III T3, T4 N2 M0
IV Any T Any N M1

Illustrated Stages of Oropharyngeal (HPV+) Cancer






Classifying & Staging Nasopharyngeal Cancer

Classification Definition
Tumor (T)
TX Primary tumor cannot be assessed.
T0 No tumor identified, but EBV-positive cervical node(s) involvement.
Tis Carcinoma in situ.
T1 Tumor confined to nasopharynx (behind nasal cavity/upper part of throat), or extension to oropharynx and/or nasal cavity without parapharyngeal involvement.
T2 Tumor with extension to parapharyngeal space, and/or adjacent soft tissue involvement (medial pterygoid, lateral pterygoid, prevertebral muscles).
T3 Tumor with infiltration of bony structures at skull base, cervical vertebra, pterygoid structures, and/or paranasal sinuses.
T4 Tumor with intracranial extension, involvement of cranial nerves, hypopharynx, orbit, parotid gland, and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid muscle.
Node (N)
NX Regional lymph nodes cannot be assessed.
N0 No regional lymph node metastasis.
N1 Unilateral (on one side) metastasis in cervical lymph node(s) and/or unilateral or bilateral metastasis (on both sides) in retropharyngeal lymph node(s), 6 cm or smaller in greatest dimension, above the caudal border of cricoid cartilage.
N2 Bilateral metastasis in cervical lymph node(s), 6 cm or smaller in greatest dimension, above the caudal border of cricoid cartilage.
N3 Unilateral (on one side) or bilateral (on both sides) metastasis in cervical lymph node(s), larger than 6 cm in greatest dimension, and/or extension below the caudal border of cricoid cartilage.
Metastasis (M)
M0 No distant metastasis.
M1 Distant metastasis.
Stage T N M
0 Tis N0 M0
I T1 N0 M0
II T0, T1, T2
T2
N1
N0
M0
M0
III T0, T1, T2, T3
T3
T3
N2
N0
N1
M0
M0
M0
IVA T4
T4
T4
Any T
N0
N1
N2
N3
M0
M0
M0
M0
IVB Any T Any N M1

Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original and primary source for this information is the AJCC Cancer Staging Manual, Eighth Edition (2017) published by Springer Science+Business Media.

Illustrated Stages of Nasopharyngeal Cancer





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