Table of Contents:

1. Welcome message
2. Introduction to the disease
3. Oral Cavity Cancer
4. Oropharynx Cancer
5. Nasopharynx Cancer
6. Hypopharynx Cancer
7. Larynx Cancer

Welcome to the AHNS Mucosal Cancer Section patient information page.

This webpage serves as an introduction to mucosal cancers in the head and neck region. These cancers can involve the oral cavity, oropharynx, nasopharynx, hypopharynx, and larynx. Cancers in this area can result in cosmetic and functional side effects, such as lip weakness, numbness, change in speech and swallowing. If you or your loved one has developed a cancer in this region, you can follow this link to search for a surgeon nearby who specializes in treating head and neck cancers.

We hope this content will help you find the information you need about head and neck cancers.

Developed by the AHNS Mucosal Section Patient Education Subcommittee

Ryan S. Jackson, MD
Rizwan Aslam, MD

We would like to thank the following Co-Authors for their contributions to developing the content on this website:
Yelizaveta Shnayder, MD; C. Burton Wood, MD; Mihir Patel, MD; Tabitha Galloway, MD; Michael Sim, MD; Heather Edwards, MD; Caitlin McMullen, MD; Joshua Lubek, MD; Neerav Goyal, MD; Catherine Lumley, MD; Eleni Rettig, MD

INTRODUCTION TO THE DISEASE

Cancers of the head and neck occur in the mucosal lining of mouth or throat and are classified by location: oral cavity (mouth), oropharynx (throat), nasopharynx (back of the nose), hypopharynx (part of the throat just before the esophagus), and larynx (voicebox). Cancers from these sites are commonly treated with one or more of the following treatments: surgery, radiation, chemotherapy. Multiple specialties participate in the treatment of such cancers, such as head and neck surgeons, radiation oncologists and medical oncologists. It is also common to undergo different imaging studies such as MRI, CT and/or PET/CT scans to determine the size and extent of the cancer, and to determine whether it has spread. Biopsies are often performed to confirm the diagnosis. Lastly, other providers such as speech and language pathologists, physical therapists, psychologists and nutritionists are often involved in the care and rehabilitation of patients with these cancers.

1. Oral cavity
   1. Anatomy
      1. The oral cavity is the space between the lips anteriorly to the back end of the hard palate (bony roof of the mouth) and the circumvallate papillae (large taste buds that mark the boundary between the oral tongue and the base of tongue tongue). The oral cavity includes the lips, gums, oral tongue, hard palate, buccal mucosa (inner lining of the cheek), and floor of the mouth.
      2. The lining or mucosa of the oral cavity is composed of squamous cells. Squamous cell carcinoma is the most common type of oral cavity cancer, which develops when squamous cells transform into a cancer. Other types of oral cavity cancers also include minor salivary cancer which arise from the saliva-producing glands within the mouth.

1. Risk Factors
   1. Both tobacco and alcohol consumption are the main risk factors for development of oral squamous cell carcinoma
      1. The cancer risk is far greater with combined exposure to tobacco or alcohol, rather than either alone.
   2. Smokeless tobacco has also been shown to increase the risk up to twofold

• Chewing betel (areca nut) is a risk factor
  1. Most commonly seen in South Asia populations

1. Poor oral hygiene and ill-fitting dentures leading to mechanical trauma may contribute to precancerous lesions and cancer of the oral cavity

1. Early symptoms of an oral cancer
   1. Non-healing sore
   2. Growing mass inside the mouth

• White or red patch inside the mouth

1. Bleeding inside the mouth
2. Oral pain
3. Ear pain

• Trouble chewing or swallowing
• Loose teeth

1. Difficulty or change in speech

1. Diagnosis
   1. Once a suspicious growth, ulcer or lesion is identified within the oral cavity, a biopsy of the suspected area will be required to confirm the diagnosis of an oral cavity mucosal malignancy. Very often the biopsy can be performed in the office using both topical and local anesthesia. Occasionally a loose tooth is an indication of an oral cavity gingival (gum) cancer, and biopsy will also include extraction of the associated tooth along with the mucosal gingival tissue. Brush biopsy or a superficial scraping of mucosal cells does not provide enough tissue and a formal biopsy will be necessary to establish a diagnosis. Further evaluation of the cancer will include a complete head and neck exam and possible in-office fiberoptic camera exam to assess the extent of the cancer within the mouth or evidence of a second malignancy within other areas of the head and neck.
   2. Your doctor may also order a variety of medical imaging including computerized tomogram imaging (CT scan), magnetic resonance imaging (MRI), positron emission tomography (PET) and dental imaging (cone beam scan or Panorex). These images will help to further delineate the extent of the cancer. Different types of imaging help to visualize different anatomic structures. For example,  CT scans and dental imaging are particularly useful for visualizing the integrity of the jaw bones. Intravenous contrast enhanced CT scan and MRI can identify abnormalities in the mouth, jaw bone marrow or neck that suggest cancer spread. PET imaging is a special technology that identifies a glucose (sugar) molecule being absorbed by the cancer cells and help identify tumor in other parts of the body. Dental imaging also assesses the dental health in the event that radiation therapy is required.

• Human papillomavirus (HPV) testing is not indicated for oral cavity squamous cell cancers, because oral cavity cancers are rarely caused by HPV.

1. Staging
   1. The American Joint Committee on Cancer (AJCC) has created a staging system (TNM staging) to help guide treatment. The staging system groups cancers into stages based on their anatomic extent. The staging helps to determine the optimal treatment for a specific cancer, and provides information about expected survival rates.
   2. The staging system includes information about the extent of the original or local tumor (T classification or primary tumor extent), spread to lymph nodes (N-classification or nodal metastases), and spread to distant parts of the body (M classification or distant metastases). Combinations of T, N and M-classifications produce an overall stage. There are four stages (Stage 1-4) reported with increasing disease burden and potentially worse survival as the AJCC overall stage number increases. In the oral cavity, factors that play a role in overall tumor stage include destruction of adjacent jaw bone; tumor thickness; appearance of the cancer cells under microscopic examination by the pathologist; and involvement of lymph nodes within the neck.

• Lymph nodes are small oval shaped structures found within the fat of the neck that harbor specialized immune cells that filter and fight infection and disease. Cancer cells from the mouth detach from the cancer and can become trapped within the individual nodes. Once an oral cancer spreads to lymph nodes, it is considered more advanced, and is considered overall stage 3 or higher. In addition, the number of abnormal lymph nodes and their size is important. Sometimes, the cancer in a lymph node grows out of the lymph node, a property known as extranodal extension (ENE). A special subclassification for the lymph nodes is designed to report on the involvement cancer (number of nodes involved with cancer and size in centimeters within the lymph nodes of the neck, as well as ENE. This information affects a tumor’s stage, and anticipated survival.

 

Primary Tumor Stage: Oral Cavity
Stage	Description
TX	Primary tumor cannot be assessed
Tis	Carcinoma in situ
T1	Tumor <= 2 cm, depth of invasion <= 5  mm
T2	Tumor <= 2 cm, depth of invasion > 5  mm and < 10 mm; or, Tumor > 2 cm but <= 4 cm, depth of invasion <= 10 mm
T3	Tumor > 4 cm; or, Tumor any size, depth of invasion > 10 mm and <= 20 mm
T4a	Extrinsic muscle of tongue involved, including extensive tumors with bilateral tongue involvement and/or depth of invasion >20 mm
T4b	Very advanced local disease; tumor invades masticator space, pterygoid plates, skull base, and/or encases the internal carotid artery

 

Regional Nodal Stage: Oral Cavity
N0	No regional lymph node metastasis
N1	Metastasis to a single ipsilateral lymph node <= 3 cm and ENE-
N2a	Metastasis to a single ipsilateral lymph node > 3 cm but not > 6 cm and ENE-; or, Single ipsilateral lymph node <= 3 cm and ENE+
N2b	Metastasis to multiple ipsilateral lymph nodes <= 6 cm and ENE-
N2c	Metastasis to bilateral lymph nodes or contralateral lymph nodes <= 6 cm and ENE-
N3a	Metastasis to any lymph node > 6 cm and ENE-
N3b	Metastasis to ipsilateral lymph node > 3 cm and ENE+; or, Multiple ipsilateral, bilateral, or contralateral lymph nodes and ENE+; or, Single contralateral node any size and ENE+

 

AJCC Prognostic Stage Groups: Oral Cavity
Stage	Description
0	TisN0M0
I	T1N0M0
II	T2N0M0
III	T3N0M0, T1N1M0, T2N1M0, or T3N1M0
IVA	T4aN0M0, T4aN1M0, T1N2M0, T2N2M0, T3N2M0, or T4aN2M0
IVB	T4b, any N, and M0
IVC	Any T, any N, and M1

 

1. Treatment
   1. The treatment of oral cavity cancers typically starts with surgery in which the primary tumor is removed along with the at risk or involved lymph nodes in the neck in a procedure called a neck dissection. Depending on the final pathology analysis, further therapy with radiation therapy or even chemoradiation therapy may be recommended to optimize chances of survival. In some patients with more favorable pathology findings, surgery alone without further added treatment is possible.
   2. Some patients who undergo surgery for treatment of oral cavity cancers may also require a reconstructive procedure, usually performed at the same time as the cancer operation, to rebuild what is lost in removing the cancer. The purpose of reconstruction is to optimize speech and swallowing. Reconstruction can consist of a skin graft, a local flap from within the mouth rotated into the defect, or a free flap. A free flap consists of parts of tissue from the patient’s own body that can be transplanted into the mouth to restore form and function that otherwise would be lost without reconstruction. This is a complex procedure that involves using techniques under the microscope to carefully reconnect the blood vessels of the tissue transplant to the recipient vessels in the neck to provide a successful reconstruction.
2. Survival
   1. Survival depends on how advanced the cancer is at diagnosis. The earlier the stage of the cancer, the higher the chance of survival. Delays in diagnosis and treatment may contribute to worse survival. But with aggressive therapy, even advanced oral cavity cancers that are stage IV are potentially curable.
   2. Treatment of oral cavity cancer can have lasting side effects such as change in speech, change in diet, difficulty swallowing, dry mouth, neck scars, tissue stiffening, and change in how you look.

• Side effects can especially be worsened if added therapy such as radiation is needed.

1. But with advances in reconstructive surgery for head and neck cancer, functional and cosmetic outcomes after surgery are continuing to improve.

1. Surveillance/Survivorship
   1. Surveillance: As with any cancer, there is a risk that oral cavity cancer will come back (‘recur’) after treatment. ‘Surveillance’ means that your doctor(s) will monitor you after treatment with a combination of physical examination and imaging studies in order to detect disease that has recurred early. Some of these visits may be transitioned to a special survivorship clinic. Protocol details will vary from institution to institution. Surveillance typically lasts for at least 5 years. Once cleared by the treating physician, patients may transition into a cancer surveillance/survivorship clinic, often run by an advanced practice provider (APP) that is well trained in head and neck cancer surveillance.
      1. Physical examination: Your doctor(s) will examine you according to the following schedule:
         1. Year One: every 1-3 months
         2. Year Two: every 2-6 months
         3. Years Three through 5: every 4-8 months
         4. After 5 years: every 12 months or as needed
      2. Imaging: The timing and type of imaging you have will be based on your doctor’s judgment and the initial tumor stage.
         1. It is sometimes recommended to have baseline imaging within 6 months of completing treatment.
         2. Imaging may include CT scans, PET/CT scans, MRI, or sometimes ultrasound.
         3. Additional imaging will be based on your symptoms, exam, and your doctor’s judgment.
         4. It is important to let your doctor know if you feel a new persistent pain or neck mass.
      3. Survivorship: Oral cavity cancer and its treatment can affect many areas of your health and quality of life. ‘Survivorship’ refers to caring for your health and well-being from the moment you receive your diagnosis, and for the rest of your life. Depending what your treatment involves, important parts of survivorship for oral cavity cancer may include:
         1. Speech and swallowing evaluation and therapy: Speech-Language Pathologist, or SLP, with expertise in speech and swallowing for head and neck cancer patients may help you to retain or regain function lost as a result of your cancer or its treatment.
            1. Swallowing: Safe swallowing is important for your health and quality of life. Poor swallowing function, called ‘dysphagia’, can lead to health problems such as pneumonia or malnutrition, and may lead to the need for a feeding tube for nutritional support. You may also be referred to a dietician for guidance on how to maintain a nutritious diet even if you have dysphagia.
            2. Speech: Rehabilitation of your speaking is important for your communication and quality of life.
         2. Oral and dental health: Oral cancer and its treatment can have a major impact on your teeth, taste, saliva and jaw bone health.
            1. Dental cleaning and care: Oral cancer patients should establish care early after diagnosis, ideally before treatment, with a dentist who has experience in head and neck cancer. Some dental work may be necessary prior to treatment. In the long term, patients should have routine cleaning and examination. Routine fluoride treatments may be recommended.
            2. Radiation and dental health: In addition to the destructive effects of oral cavity cancer itself and surgery, radiation can be detrimental to your dental health. It is especially important for patients who undergo radiation to have regular dental care and excellent dental hygiene.
            3. Dry mouth: Dry mouth, or ‘xerostomia’, is common after radiation therapy and can have a significant negative impact on quality of life. There is no cure for xerostomia. If you have xerostomia, you can decrease the symptoms by staying hydrated, using salivary substitutes, and maintaining excellent dental hygiene.
            4. Osteoradionecrosis (ORN): Patients who undergo radiation are at risk for breakdown of the jaw bone, or osteoradionecrosis (ORN). This may cause ulcerations, exposed bone, pain, and chronic infection. ORN is diagnosed with history, examination and imaging. Treatment may involve medications, hyperbaric oxygen treatments, or in advanced cases, bone removal and reconstruction.
            5. Dental restoration: A prosthodontist with experience treating oral cancer patients may be able to restore lost dentition and fabricate obturators for defects of the palate. Ask your doctor for a referral to a prosthodontist if you are interested in learning about your dental restoration options.
            6. Trismus: Surgery and radiation can cause difficulty opening your mouth, called trismus. This can interfere with dental care and with eating. Ask your doctor about ways to manage your trismus.
         3. Thyroid function testing: If you have had radiation therapy, you have an increased risk of low thyroid function, or ‘hypothyroidism’. Symptoms of hypothyroidism may include fatigue, weight gain, constipation and depression. Your thyroid function should be tested every 6-12 months to determine whether you need treatment with thyroid hormone supplementation.
         4. Tobacco use:
            1. Most head and neck cancers are associated with tobacco use, especially smoking cigarettes.
            2. Continued tobacco use after treatment is associated with worse survival and higher risk of other cancers, among many other negative health effects.
            3. Quitting tobacco at any time will improve your overall health and chances of survival from head and neck cancer.
            4. If you still use tobacco after head and neck cancer treatment, we strongly encourage you to consider quitting. Your doctor can help you find resources, including medications and counseling programs, that have been proven to help.
         5. Lymphedema: Lymphedema is swelling of the soft tissue that is common for patients who have had surgery and/or radiation. Specialized Physical Therapy called Lymphedema Therapy, including massage, compression garments, exercises and skin care, is available and can significantly improve lymphedema.
         6. Shoulder dysfunction: Many head and neck cancer survivors have shoulder dysfunction, including decreased range of motion, weakness and stiffness as a result of surgery and/or radiation. Physical therapy is very helpful in improving shoulder function. If you have problems with your shoulder, ask your doctor about a referral to a physical therapist.
         7. Obstructive sleep apnea: Survivors of head and neck cancer treatment are at risk for obstructive sleep apnea (OSA) because of changes to the upper airway anatomy. Symptoms may include daytime sleepiness, snoring, gasping or choking during sleep, daytime headaches, and irritability. OSA is diagnosed with a sleep study, and there are several options for treatment. Discuss your risk of OSA with your doctor.
         8. Carotid artery stenosis evaluation: Radiation therapy to the neck increases the risk of carotid artery narrowing (stenosis) later in life. Carotid artery stenosis increases the risk of stroke. If you have had radiation to your neck, ask your doctor about an ultrasound or carotid doppler study to look for carotid artery stenosis.
         9. Mental and sexual health: Head and neck cancer and its treatment can result in cognitive dysfunction, anxiety, depression, body image concerns, and changes in sexual function and desire. If you suffer from any of these, you are not alone. Ask your doctor about meeting with a mental health professional to determine whether counseling and/or medication may be helpful for you.
         10. Hearing evaluation: Head and neck cancer treatments, especially with certain chemotherapy drugs, can cause hearing loss. If you have decreased hearing, you should have a hearing test to evaluate your hearing and determine whether you may benefit from hearing augmentation, such as with a hearing aid.
      4. Questions for your doctor
         1. Before/during treatment:
            1. What types of treatment are recommended (such as surgery, radiation, and/or chemotherapy)?
            2. Are there any other treatment options that I should learn about, such as clinical trials?
            3. Should I see a dentist before treatment begins?
            4. How long will treatment take? How long will it take to fully recover after treatment?
            5. What are the risks and side effects of each part of treatment? Which side effects are temporary, and which might be permanent?
            6. Will I need a feeding tube or a breathing tube (tracheostomy)? Will they be temporary or permanent?
            7. What will my swallowing, speech and breathing be like after treatment?
            8. Will I have any other functional problems after treatment?
            9. Will I be able to keep doing my job after I’ve recovered?
         2. After treatment:
            1. Should I have any imaging studies?
            2. When should my next follow-up appointment be, and with whom?
            3. Should I have my thyroid function tested?
            4. Should I be referred to a speech and language pathologist (SLP), and or to a physical or occupational therapist?
            5. Am I receiving appropriate dental care?
            6. Are there any options for dental rehabilitation for me?
            7. Should I have a sleep study?
            8. Do I need a carotid artery ultrasound?
            9. Should I have a hearing test?

 

2. Oropharynx
   1. Anatomy
      1. The oropharynx is an area in the back of your mouth and upper throat. This begins from the soft palate, the very back of the tongue, and the tonsils and extends to the back of the throat.  From top to bottom, this area extends from the level of the soft palate to the root of the epiglottis (the lid that covers the voice box upon swallowing to help direct food into the esophagus or swallow tube).  Within the oropharynx there are two sets of tonsil tissue.  The palatine tonsils are located on the side of the throat and more commonly referred to as tonsils and are most commonly removed surgically after multiple infections. The second set of tonsils, lingual tonsils, are positioned at the very back of the tongue, also known as the tongue base.
      2. The oropharynx plays a very important role in normal swallowing. The oropharynx functions to direct and push food down to the esophagus in a coordinated effort. First the soft palate moves up and backward to touch the back of the throat, preventing food and liquid from traveling into the nasal passage.  The tongue base moves back and downward, driving food down toward the esophagus.  At the same time, the epiglottis turns down to cover the entrance to the voice box, protecting food from entering the “windpipe” (trachea) and lungs.

• Squamous cells make up the lining, also known as the mucosa, of the oropharynx. That is why squamous cell carcinoma is the most common type of oropharynx cancer. Lymphomas and tumors arising from saliva producing glands can also occur in this location.

 

1. Risk Factors
   1. Historically oropharyngeal cancer was mostly associated with tobacco and alcohol consumption, more recently the most common risk factor is the Human Papilloma Virus (HPV), a virus which also causes cervical cancer.
      1. HPV associated oropharyngeal SCC has been rising, especially among younger age groups
      2. HPV can be associated with oral sexual behaviors
         1. Risk increases with > 11 vaginal sex partners and 6 oral sex partners
      3. HPV cancer may also be related to marijuana use
      4. Poor dental hygiene may be associated with non-HPV associated oropharyngeal cancer

 

1. Symptoms
   1. It is common for patients with HPV associated oropharyngeal cancer to present with a painless neck mass
   2. Symptoms of oropharynx cancer:
      1. Neck mass
      2. Sore throat
      3. Voice or speech changes
      4. Ear pain
      5. Spitting out blood
      6. Difficulty or pain with swallowing

 

1. Diagnosis
   1. Once a suspicious growth, ulcer or lesion is identified within the oropharynx (tongue base, soft palate, tonsil) a biopsy of the suspected area will be required to confirm the diagnosis of an oropharyngeal mucosal malignancy. Due to the location of the cancer, a biopsy at your doctor’s office using both topical and local anesthesia may be difficult. To effectively biopsy and evaluate the extent of the oropharyngeal cancer, you may require biopsy under general anesthesia in the operating room. Prior to scheduling your biopsy under general anesthesia, a complete head and neck exam including possible in-office fiberoptic camera exam may be performed.
   2. Patients presenting with a neck, mass may undergo a needle biopsy in the office with or without radiologic image or ultrasound guidance.

• Biopsies are often tested for HPV or p16 to determine if the cancer is related to the Human Papillomavirus.

1. Your doctor may also order a variety of medical imaging:
   1. Computerized tomogram imaging (CT scan)
   2. Magnetic resonance imaging (MRI)
   3. Positron emission tomography (PET)
   4. Dental imaging (cone beam scan or Panorex).

These images will help to further delineate the extent and spread of the cancer. The CT scan and dental imaging will help to identify disease within the jaw bone (mandible or maxilla) and condition of the teeth. Intravenous contrast enhanced CT scan and MRI can identify soft tissue structures within tongue, tonsil, palate, throat or neck that may have disease. PET imaging is a special technology that identifies a glucose (sugar) molecule being absorbed by the cancer cells and help determine whether the cancer has spread to other parts of the body. Alternatively, CT scan imaging of the chest may be performed to visualize any spread of disease to the lungs.

1. In some patients, the primary oropharynx cancer site may be undetectable on examination. Your doctor may recommend removal of the tonsils and superficial surface of the tongue base under general anesthesia to identify the tumor where it started.

1. Staging
   1. The American Joint Committee on Cancer (AJCC) has created a staging system (TNM staging that groups cancers into stages based on their anatomic extent. The staging helps to determine the optimal treatment for a specific cancer, and provides information about expected survival rates.
   2. The staging system includes information about the extent of the original or local tumor (T classification or primary tumor extent), spread to lymph nodes (N-classification or nodal metastases), and spread to distant parts of the body (M classification or distant metastases). Combinations of T, N and M-classifications produce an overall stage. There are four stages (Stage 1-4) reported with increasing disease burden and potentially worse prognosis as the AJCC stage number increases.

• Human papillomavirus (HPV) causes most oropharyngeal mucosal cancers. Identification of this virus within the biopsy specimen and/or following surgical tumor removal is essential for accurate staging and prognosis.

1. New AJCC staging guidelines (8^th edition) has a different staging system for oropharynx cancers caused by HPV and those not caused by HPV. In general terms, patients with HPV-positive tumors of the oropharynx have a better long-term survival and less aggressive disease than HPV-negative oropharynx cancers, even if the cancer has already spread to lymph nodes.
2. Lymph nodes are small oval shaped structures found within the fat of the neck that harbor specialized immune cells that filter and fight infection and disease. Cancer cells from the mouth detach from the cancer and can become trapped and grow within the individual nodes.
3. For HPV negative cancers, the number of abnormal lymph nodes and their size is important. Sometimes, the cancer in a lymph node grows out of the lymph node, a property known as extranodal extension (ENE). A special subclassification for the lymph nodes is designed to report on the involvement cancer (number of nodes involved with cancer and size in centimeters within the lymph nodes of the neck, as well as ENE.

• The staging system includes different criteria for HPV positive and HPV negative cancers, even though both types originate in the squamous cells in the mucosal lining of the oropharynx. For HPV positive cancers, the spread of cancer to lymph nodes does not have the same negative effect on survival. HPV-related cancers that spread to lymph nodes may still represent early-stage disease. In contrast, HPV-negative cancers that have spread to lymph nodes are considered at least Stage 3.

 

Primary Tumor Stage: HPV-related Oropharynx
Stage	Description
T0	No primary tumor identified
T1	Tumor 2 cm or smaller
T2	Tumor larger than 2 cm but not larger than 4 cm
T3	Tumor larger than 4 cm; or, Tumor extends to lingual surface of the epiglottis
T4a	Tumor invades larynx, extrinsic muscles of tongue, medial pterygoid, hard palate, or mandible or beyond

 

Regional Nodal Stage: HPV-related Oropharynx
Clinical Stage	Description
N0	No regional lymph node metastasis
N1	One or more ipsilateral lymph node, none larger than 6 cm
N2	Contralateral or bilateral lymph nodes, none larger than 6 cm
N3	One or more lymph node larger than 6 cm

 

Regional Nodal Stage: HPV-related Oropharynx
Pathologic Stage	Description
pNX	Regional lymph nodes cannot be assessed
pN0	No regional lymph node metastasis
pN1	Metastasis in 4 or fewer lymph nodes
pN2	Metastasis in more than 4 lymph nodes

 

AJCC Prognostic Stage Groups: HPV-related Oropharynx
Clinical Stage	Description
I	T0-2, N0-1, and M0
II	T0-2, N2, M0; or, N3, N0-2, M0
III	T0-4, N3, M0; or, T4, N0-3, M0
IV	Any T, any N, M1

 

AJCC Prognostic Stage Groups: HPV-related Oropharynx
Pathologic Stage	Description
I	T0-3, N0-1, M0
II	T0-2, N2, M0; or, T3-4, N0-1, M0
III	T3-4, N2, M0
IV	Any T, any N, M1

 

Primary Tumor Stage: HPV-negative Oropharynx
Stage	Description
Tx	Primary tumor cannot be assessed
Tis	Carcinoma in situ
T1	Tumor 2 cm or smaller
T2	Tumor larger than 2 cm but not larger than 4 cm
T3	Tumor larger than 4 cm; or, Tumor extends to lingual surface of the epiglottis
T4a	Tumor invades larynx, extrinsic muscles of tongue, medial pterygoid, hard palate, or mandible
T4b	Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base or encases carotid artery

 

Regional Nodal Stage: HPV-negative Oropharynx
Stage	Description
Nx	Regional lymph nodes cannot be assessed
N0	No regional lymph node metastasis
N1	Metastasis in a single ipsilateral node, 3 cm or smaller and ENE (-)
N2a	Metastasis in a single ipsilateral node 3 cm or less and ENE (+); or, A single ipsilateral node larger than 3 cm but not larger than 6 cm and ENE (-)
N2b	Metastases in multiple ipsilateral lymph nodes, none larger than 6 cm and ENE (-)
N2c	Metastasis in bilateral or contralateral lymph nodes, none larger than 6 cm and ENE (-)
N3a	Metastasis in a lymph node larger than 6 cm and ENE (-)
N3b	Metastasis in a single ipsilateral node larger than 3 cm and ENE (+); or, Multiple ipsilateral, contralateral or bilateral nodes, any with ENE (+); or, A single contralateral node any size and ENE (+)

 

AJCC Prognostic Stage Groups: HPV-negative Oropharynx
Stage	Description
0	TisN0M0
I	T1N0M0
II	T2N0M0
III	T3N0M0, T1-3N1M0
IVA	T4aN0-1M0, T1-4aN2M0
IVB	Any T, N3, M0; or, T4b, any N, M0
IVC	Any T, any N, and M1

 

1. Treatment
   1. Typically, patients have a team that includes a head and neck surgeon, medical oncologist, radiation oncologist, nurse practitioner or physician assistant (APP), and speech language pathologist (SLP) who will determine treatment options at your initial visit.
   2. Squamous cell carcinoma of the oropharynx is effectively treated with surgical and non-surgical options. Patients with a significant history of smoking, regardless of HPV-status are most commonly treated with radiation therapy combined with chemotherapy (typically cisplatin) administered concurrently (during the same 6-week-long interval). Patients with HPV-driven squamous cell carcinoma are staged differently due to higher survival rates.  As such, many patients with HPV-driven oropharynx cancer are actively being treated with lower doses of radiation therapy combined with chemotherapy and/or immunotherapy (currently only in the setting of clinical trials), to try and reduce the side effects of high dose radiation while maintaining high cure rates. For this reason, treatment options vary and may continue to change as information from clinical trials becomes available.

• The current standard of care for non-surgical therapy is radiation to 70 Gy combined with cisplatin. Depending on the tumor stage and extent, patients may be eligible for treatment with radiation alone, without chemotherapy.

1. Some patients with oropharynx cancers may be candidates for surgical removal of their cancers. Transoral surgery (i.e. surgery through the mouth) is a surgical approach to tumor removal in a less invasive manner than traditional surgery, resulting in a quicker recovery and fewer complications. Transoral surgery is performed with a microscope or a robotic device to enhance the ability to see in a small space.  TransOral Robotic Surgery (TORS) specifically refers to using a robot during surgery. It uses a computer system to guide the surgical tools which is controlled by a trained surgeon. Using a robotic system to guide the tools allows for more precise movements and allows the surgeon to be able to operate in small spaces with 3-D visual magnification. TORS is FDA approved for removing smaller tonsil and tongue base cancers (i.e. classified as T1 or T2 tumors). The overwhelming majority of surgically treated patients also require surgery to remove the lymph nodes in the neck that may contain cancer or are at risk for harboring cancer. Approximately 70-90% of patients who undergo surgery will require postoperative radiotherapy, and 25-50% will require chemotherapy. Transoral surgery is typically performed for the following reasons:
   • To reduce the dose of radiation treatment received to the neck and throat
   • To prevent the need for extra treatments such as chemotherapy

The survival and swallowing of patients who undergo initial surgery followed by radiation appears to be favorable, but head to head comparisons have not been performed. Long term effects of different treatment approaches have also not been well described but are active areas of investigation.

1. Survival
   1. Initial cancers stage is the most important factor to affect survival for oropharynx cancer patients. A higher stage suggests a more advanced cancer and a lower survival. We also know, for the oropharynx, cancers that are related to the human papilloma virus (HPV) tend to do better than similar cancers not caused by this virus. In general, the overall 5-year survival associated with oropharynx cancer as reported by the American Cancer Society is 67% not considering a patient’s age, smoking or alcohol history, or HPV status. Early cancers have a reported 5-year survival of 84% which decreases to 66% if the lymph nodes are involved and to 39% if distant organs are involved.
   2. In addition to considering survival, it is important to discuss the impact that the cancer and cancer treatment can have on a person’s overall function and lifestyle. For patients who undergo surgery for oropharyngeal cancers, changes in appearance may be minimal, though there can be external scars related to the removal of neck lymph nodes. For more advanced cancers, surgery may involve complex reconstruction which may have other associated scars which your surgeon can discuss in more detail. Surgery can also impact your swallowing which is discussed below.

• For those patients who require non-surgical treatment such as radiation with or without chemotherapy, the treatment can have other effects. Short term side effects, that occur during and immediately after treatment, include mucositis, rashes, nausea and vomiting, weight loss, pain including pain with eating or swallowing, and muscle aches. Mucositis refers to sores that can occur inside the region receiving radiation treatment and can include the mouth and throat. This can make swallowing painful. Your doctors may prescribe medications to help numb the throat in the area to make the sores more tolerable. The sores typically resolve after completing treatment. Patients who are getting radiation to the face and neck can develop a red rash with peeling and dry skin in the areas receiving radiation. This can be worsened by certain types of chemotherapy. Often moisturizers and skin emollients are prescribed to help manage the skin. Nausea and vomiting are seen more often in patients also receiving chemotherapy and your doctors may prescribe specific medications to help manage these symptoms. These symptoms may make it difficult to get adequate nutrition, and weight loss is common. Some patients require a stomach tube to maintain their weight and support their nutrition.

1. Long term side effects can include taste dysfunction, dry mouth, trouble swallowing, neck and facial swelling (or lymphedema), hearing loss and nerve pain or neuropathy. For many patients their taste is altered during and immediately following radiation treatment and recovers to some degree in the months following treatment. Taste changes can include a lack of taste or food tasting too sweet or too salty or burning.
2. Many patients suffer from dry mouth or xerostomia following radiation therapy as the saliva glands are particularly sensitive to radiation. This can lead to thickened saliva in the mouth and generally a dry mouth feel. This may be permanent. Many patients are accompanied by a water bottle, and take sips frequently. Additionally, certain over the counter saliva substitutes can help keep the mouth moist. Sugar free gum can also help improve saliva production.
3. In addition to affecting saliva, radiation treatment can also affect swallowing. The radiation therapy can stiffen the swallowing muscles making it harder to get the food to go down. Patients report feeling persistent “phlegm”. Surgery can also worsen swallowing by altering normal anatomy, causing scar tissue and changes in sensation or feeling in the back of your throat. Swallow therapists (known as speech-language pathologists) can help patients strengthen and coordinate their swallowing muscles to improve their swallowing.

• Certain chemotherapy drugs can lead to hearing loss or ringing in the ears. Your doctor may check your hearing before and after treatment. The effect to your hearing is usually related to a nerve related damage which may not recover. If the effect is significant, a hearing aid may need to be considered to help treat the hearing loss. Both radiation and chemotherapy can lead to long term nerve and muscle pains. The likelihood of this occurring is related to the amount of chemotherapy and radiation you receive. Some effects lessen the further out from treatment you are.
• References:

American Cancer Society. Cancer Facts & Figures 2020. Atlanta: American Cancer Society; 2020.

 

1. Surveillance/Survivorship
   1. Surveillance: As with any cancer, there is a risk that oropharynx cancer will come back (‘recur’) after treatment. ‘Surveillance’ means that your doctor(s) will monitor you after treatment with a combination of physical examination and imaging studies in order to detect recurrent disease early. Protocol details will vary from institution to institution. Patients will be followed for at least 5 years. Once cleared by the treating physician, patients may transition into a cancer surveillance/survivorship clinic, often run by an advanced practice provider (APP) that is well trained in head and neck cancer surveillance.
      1. Physical examination: Your doctor(s) will examine you according to the following schedule:
         1. Year One: every 1-3 months
         2. Year Two: every 2-6 months
         3. Years Three through 5: every 4-8 months
         4. After 5 years: every 12 months or as needed
      2. Imaging: The timing and type of imaging you have will be based on your doctor’s judgment.
         1. Baseline imaging within 6 months of completing treatment may be considered.
         2. Imaging may include CT scans, PET/CT scans, MRI, or sometimes ultrasound.
         3. Additional imaging will be based on your symptoms, exam, and your doctor’s judgment.
         4. It is important to let your doctor know if you feel a new persistent pain or neck mass.

 

1. Survivorship: Oropharynx cancer and its treatment can affect many areas of your health and quality of life. ‘Survivorship’ refers to caring for your health and well-being from the moment you receive your diagnosis, and for the rest of your life. Depending what your treatment involves, important parts of survivorship for oropharynx cancer may include:
   1. Speech and swallowing evaluation and therapy: This is typically with a Speech-Language Pathologist, or SLP, with expertise in speech and swallowing for head and neck cancer patients.
      1. Swallowing: Safe swallowing is important for your health and quality of life. Poor swallowing function, called ‘dysphagia’, can lead to health problems such as pneumonia or malnutrition, and may lead to the need for a feeding tube. You may also be referred to a dietician for guidance on how to get adequate nutrition to maintain your health.
      2. Esophageal stricture: Some patients develop a narrowing of your esophagus, called an ‘esophageal stricture’. This can be diagnosed with a swallowing test. Some patients benefit from having their esophagus stretched.
      3. Speech: Rehabilitation of your speaking is important for your communication and quality of life.
   2. Oral and dental health: Oropharynx and its treatment can have a major impact on your teeth, taste, saliva and jaw bone health.
      1. Dental cleaning and care: Oropharynx cancer patients should establish care early after diagnosis, ideally before treatment, with a dentist who has experience in head and neck cancer. Some dental work may be necessary prior to treatment. In the long term, patients should have routine cleaning and examination. Routine fluoride treatments may be recommended.
      2. Radiation and dental health: Radiation can be detrimental to your dental health. Without the protective enzymes in you saliva that protect your teeth and gums from harmful bacteria, your teeth become susceptible to severe dental caries leading to jaw infections. It is especially important for patients who undergo radiation to have regular dental care and excellent dental hygiene.
      3. Dry mouth: Dry mouth, or ‘xerostomia’, is common after radiation therapy and can have a significant negative impact on quality of life. There is no cure for xerostomia. If you have xerostomia, you can decrease the symptoms by staying hydrated, using salivary substitutes, and maintaining excellent dental hygiene.
      4. Osteoradionecrosis (ORN): Patients who undergo radiation are at risk for breakdown of the jaw bone, or osteoradionecrosis (ORN). This may cause ulcers, exposed bone, pain, and chronic infection. ORN is diagnosed with history, examination and imaging. Treatment may involve medications, hyperbaric oxygen treatments, or in advanced cases, bone removal and reconstruction.
      5. Trismus: Surgery and radiation can cause difficulty opening your mouth, called trismus. This can interfere with dental care and with eating. Ask your doctor about ways to improve your mouth opening.
   3. Thyroid function testing: If you have had radiation therapy, you have an increased risk of low thyroid function, or ‘hypothyroidism’. Symptoms of hypothyroidism may include fatigue, weight gain, constipation and depression. Your thyroid function should be tested every 6-12 months to determine whether you need treatment with thyroid hormone supplementation.
   4. Tobacco use:
      1. Most head and neck cancers are associated with tobacco use, especially smoking cigarettes.
      2. Continued tobacco use after treatment is associated with worse survival and higher risk of other cancers, among many other negative health effects.
      3. Quitting tobacco will improve your overall health and chances of survival from head and neck cancer.
      4. If you still use tobacco after head and neck cancer treatment, we strongly encourage you to consider quitting. Your doctor can help you find resources, including medications and counseling programs, that have been proven to help.
   5. Lymphedema: Lymphedema is swelling of the soft tissue that is common for patients who have had surgery and/or radiation. Specialized Physical Therapy called Lymphedema Therapy, including massage, compression garments, exercises and skin care, is available and can significantly improve lymphedema.
   6. Shoulder dysfunction: Many head and neck cancer survivors have shoulder dysfunction, including decreased range of motion, weakness and stiffness as a result of surgery and/or radiation. Physical therapy is very helpful in improving shoulder function. If you have problems with your shoulder, ask your doctor about a referral to a physical therapist.
   7. Obstructive sleep apnea: Survivors of head and neck cancer treatment are at risk for obstructive sleep apnea (OSA) because of changes to the upper airway anatomy. Symptoms may include daytime sleepiness, snoring, gasping or choking during sleep, daytime headaches, and irritability. OSA is diagnosed with a sleep study, and there are several options for treatment. Discuss your risk of OSA with your doctor..
   8. Carotid artery stenosis evaluation: Radiation therapy to the neck increases the risk of carotid artery narrowing (stenosis) later in life. Carotid artery stenosis increases the risk of stroke. If you have had radiation to your neck, ask your doctor about an ultrasound or carotid Doppler to look for carotid artery stenosis.
   9. Mental and sexual health: Head and neck cancer and its treatment can result in cognitive dysfunction, anxiety, depression, body image concerns, and changes in sexual function and desire. If you suffer from any of these, you are not alone. Ask your doctor about meeting with a mental health professional to determine whether counseling and/or medication may be helpful for you.
   10. Hearing evaluation: Head and neck cancer treatments, especially with certain chemotherapy drugs, can cause hearing loss. If you have decreased hearing, you should have a hearing test to evaluate your hearing and determine whether you may benefit from hearing augmentation, such as with a hearing aid.

 

1. Questions for your doctor
   1. Before/during treatment:
      1. Is my tumor caused by HPV? How does this affect my prognosis?
      2. What types of treatment are recommended (such as surgery, radiation, and/or chemotherapy)?
      3. Are there any other treatment options that I should learn about, such as clinical trials?
      4. Should I see a dentist before treatment begins?
      5. How long will treatment take? How long will it take to fully recover after treatment?
      6. What are the risks and side effects of each part of treatment? Which side effects are temporary, and which might be permanent?
      7. Will I need a feeding tube or a breathing tube (tracheostomy)? Will they be temporary or permanent?
      8. What will my swallowing, speech and breathing be like after treatment?
      9. Will I have any other functional problems after treatment?
      10. Will I be able to keep doing my job after I’ve recovered?
   2. After treatment:
      1. Should I have any imaging studies?
      2. When should my next follow-up appointment be, and with whom?
      3. Should I have my thyroid function tested?
      4. Should I be referred to a speech and language pathologist (SLP), and or to a physical or occupational therapist?
      5. Am I receiving appropriate dental care?
      6. Should I have a sleep study?
      7. Do I need a carotid artery ultrasound?
      8. Should I have a hearing test?

 

3. Nasopharynx
   1. Anatomy
      1. The nasopharynx is the upper most portion of the throat and connects the nasal cavity to the oropharynx. It contains the adenoids and the eustachian tube openings.
      2. Squamous cells make up the lining, also known as the mucosa, of the nasopharynx. The adenoids are lymphoid tissue. Therefore, cancers such as squamous cell carcinoma and lymphoma can occur in the nasopharynx.
   2. Risk Factors
      1. Some nasopharynx cancers are caused by the Epstein- Barr virus
      2. Cooking salt-cured fish and meat releases a chemical called nitrosamine, a chemical known to increase the risk of nasopharynx cancer

• This type of cancer occurs more frequently in Southeast Asia and China

1. Symptoms
   1. Patients commonly present with a painless neck mass
   2. Nasal congestion or ear congestion, hearing loss

• Some people could present with bloody discharge from their nose, or report worsening trouble breathing through the nose.

1. Diagnosis
   1. Once a suspicious growth or lesion is identified within the nasopharynx a biopsy of the suspected area will be required to confirm the diagnosis of nasopharyngeal carcinoma (NPC). Due to the location of the cancer within the back of the throat and nasal cavity; a biopsy at your doctor’s office using both topical and local anesthesia may be difficult. To effectively biopsy and evaluate the extent of the nasopharyngeal cancer, you may require biopsy under general anesthesia in the operating room. Prior to scheduling your biopsy under general anesthesia, a complete head and neck exam including possible in-office fiberoptic nasal camera exam may be performed.
   2. Patients presenting with a neck mass may undergo a needle biopsy in the office with or without ultrasound guidance.

• Your doctor may also order a variety of medical imaging:
  1. Computerized tomogram imaging (CT scan)
  2. Magnetic resonance imaging (MRI)
  3. Positron emission tomography (PET)
  4. Dental imaging (cone beam scan or Panorex).

1. These images will help to further determine the extent of the cancer. Different types of imaging help to visualize different anatomic structures. For example, CT scans and dental imaging are particularly useful for visualizing the integrity of the jaw bones. Intravenous contrast enhanced CT scan and MRI can identify abnormalities within tongue, tonsil, palate, throat or neck tissues. PET imaging is a special technology that identifies a glucose (sugar) molecule being absorbed by the cancer cells and help determine whether the tumor has spread to other parts of the body.

Alternatively, CT scan imaging of the chest may be used to visualize any spread of disease to the lungs. Dental imaging may also help identify disease within the jaw bones and assess the health of the teeth in the event that radiation therapy is required.

1. Staging
   1. The American Joint Committee on Cancer (AJCC) has created a staging system (TNM staging) to help guide treatment. The staging system groups cancers into stages based on their anatomic extent. The staging helps to determine the optimal treatment for a specific cancer, and provides information about expected survival rates.
   2. The staging system includes information about the extent of the original or local tumor (T classification or primary tumor extent), spread to lymph nodes (N-classification or nodal metastases), and spread to distant parts of the body (M classification or distant metastases). Combinations of T, N and M-classifications produce an overall stage. There are four stages (Stage 1-4) reported with increasing disease burden and potentially worse survival as the AJCC stage number increases. Factors that play a role in tumor stage include: destruction of adjacent structures (ie. nasal cavity, brain, orbit/eye, spine or sinuses), involvement of lymph nodes within the neck and distant metastasis.

• Epstein-Barr virus (EBV) DNA testing within the tumor and blood plasma may be performed. In the United States, a minority of nasopharynx cancers are caused by EBV.

1. Lymph nodes are small oval shaped structures found within the fat of the neck that harbor specialized immune cells that filter and fight infection and disease. Cancer cells from the nasopharynx detach from the primary tumor and become trapped within the individual nodes where they grow. The number, location and size of lymph nodes affect the tumor stage.

 

Primary Tumor Stage: Nasopharynx
Stage	Description
TX	Primary tumor cannot be assessed
T0	No primary tumor identified, but EBV+ lymph node involvement
Tis	Carcinoma in situ
T1	Tumor confined to the nasopharynx, or extension to the oropharynx and/or nasal cavity without parapharyngeal involvment
T2	Tumor with extension to the 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 plates, 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

 

Regional Nodal Stage: Nasopharynx
Stage	Description
Nx	Regional lymph nodes cannot be assessed
N0	No regional lymph node metastasis
N1	Unilateral metastasis in cervical lymph node and/or unilateral or bilateral metastasis in retropharyngeal lymph nodes above the lower border of the cricoid cartilage, <= 6 cm
N2	Bilateral metastasis in cervical lymph nodes above the lower border of the cricoid cartilage, <= 6 cm
N3	Unilateral or bilateral metastasis in cervical lymph nodes, > 6 cm, and/or extension below the lower border of the cricoid cartilage

 

AJCC Prognostic Stage Groups: Nasopharynx
Stage	Description
0	TisN0M0
I	T1N0M0
II	T0N1M0, T1N1M0, or T2N1M0
III	T0N2M0, T1N2M0, T2N2M0, T3N0M0, T3N1M0, or T3N2M0
IVA	T4N0M0, T4N1M0, T4N2M0, T0N3M0, T1N3M0, T2N3M0, T3N3M0, or T4N3M0
IVB	AnyT, any N, and M1

 

1. Treatment
   1. The best treatment for nasopharyngeal cancer depends on many factors, including the cancer stage and your general health and other medical conditions. Not everyone receives the same treatment, and you should work with a multidisciplinary team of doctors to tailor an individual treatment plan for you.
   2. Potential treatment options include clinical trials, radiation, chemotherapy, surgery, or a combination of these.

• Clinical trials study a promising treatment in people. They can allow you to access treatment options that wouldn’t otherwise be available. You can ask your oncology team if there is an open clinical trial that you can consider joining.

1. Radiation is the main treatment for early stage nasopharyngeal cancer. This treatment uses high-energy rays or particles aimed at the cancer. There are different types of radiation, including Intensity-modulated radiation therapy (IMRT), 3-dimensional conformal radiation therapy and proton therapy. Your radiation therapist will recommend the option they believe is most appropriate for your specific situation. Proton therapy is only available at certain centers.
2. Chemotherapy, targeted therapies and immunotherapy are drugs that are active against the cancer cells. Some drugs directly destroy cancer cells, while other drugs can stop cancer cells from growing or allow immune cells in your body to destroy the cancer. Most of these drugs are not effective alone, and usually combined with radiation. They can also be given before or after other treatments as part of a treatment plan.
3. Surgery is infrequently used to treat this kind of cancer, because it usually responds to radiation and chemotherapy. Surgery is sometimes used to remove lymph nodes or recurrent cancer after failure of chemotherapy and radiation.

 

1. Survival
   2015. The survival rate for nasopharyngeal cancer is strongly affected by initial tumor stage and patient overall health. Your oncology team can tell you about survival rates based on your cancer stage. However, it is important to remember that these numbers are based on groups of patients in the past, and they don’t take into account many individual factors. The American Cancer Society gives 5-year survival rates ranging from 82%-48% depending on the cancer stage. This is based on data collected between 2009 and 2015.¹
   2016. Short term side effects of treatment are common and include skin changes, tiredness, sores in the mouth and nose, loss of appetite, trouble eating or swallowing, and changes in your sense of smell and taste. Long-term side effects can include hearing or vision loss, dental problems, low thyroid hormone levels, and damage to the carotid arteries which can increase your risk of stroke. It is important to discuss the expected and possible side effects of treatment with your care team.

• American Cancer Society “Survival rates for nasopharyngeal cancer.” Accessed Oct 10, 2020. https://www.cancer.org/cancer/nasopharyngeal-cancer/detection-diagnosis-staging/survival-rates.html

 

1. Surveillance/Survivorship
   1. Surveillance: As with any cancer, there is a risk that nasopharynx cancer will come back (‘recur’) after treatment. ‘Surveillance’ means that your doctor(s) will monitor you after treatment with a combination of physical examination and imaging studies in order to detect disease that has recurred early. Protocol details will vary from institution to institution. Surveillance typically lasts for at least 5 years. Once cleared by the treating physician, patients may transition into a cancer surveillance/survivorship clinic, often run by an advanced practice provider (APP) that is well trained in head and neck cancer surveillance.
      1. Physical examination: Your doctor(s) will examine you according to the following schedule:
         1. Year One: every 1-3 months
         2. Year Two: every 2-6 months
         3. Years Three through 5: every 4-8 months
         4. After 5 years: every 12 months or as needed.
      2. Imaging: The timing and type of imaging you have will be based on your doctor’s judgment.
         1. It is recommended to have baseline imaging within 6 months of completing treatment.
         2. Imaging may include CT scans, PET/CT scans, MRI, or sometimes ultrasound.
         3. Additional imaging will be based on your symptoms, exam, and your doctor’s judgment.
      3. Blood test: Your doctor may order a blood test to look for Epstein-Barr Virus (EBV) as part of your surveillance.
   2. Survivorship: Nasopharynx cancer and its treatment can affect many areas of your health and quality of life. ‘Survivorship’ refers to caring for your health and well-being from the moment you receive your diagnosis, and for the rest of your life. Depending what your treatment involves, important parts of survivorship for nasopharynx cancer may include:
      1. Speech and swallowing evaluation and therapy: This is typically with a Speech-Language Pathologist, or SLP, with expertise in speech and swallowing for head and neck cancer patients.
         1. Swallowing: Safe swallowing is important for your health and quality of life. Poor swallowing function, called ‘dysphagia’, can lead to health problems such as pneumonia or malnutrition, and may lead to the need for a feeding tube in order to stay healthy. You may also be referred to a dietician for guidance on how to maintain a nutritious diet even if you have dysphagia.
         2. Speech: Rehabilitation of your speaking is important for your communication and quality of life.
      2. Oral and dental health: Nasopharynx cancer and its treatment can have a major impact on your teeth, taste, saliva and jaw bone.
         1. Dental cleaning and care: Nasopharynx cancer patients should establish care early after diagnosis, ideally before treatment, with a dentist who has experience in head and neck cancer. Some dental work may be necessary prior to treatment. In the long term, patients should have routine cleaning and examination. Routine fluoride treatments may be recommended.
         2. Radiation and dental health: Radiation can be detrimental to your dental health. It is especially important for patients who undergo radiation to have regular dental care and excellent dental hygiene.
         3. Dry mouth: Dry mouth, or ‘xerostomia’, is common after radiation therapy and can have a significant negative impact on quality of life. There is no cure for xerostomia. If you have xerostomia, you can decrease the symptoms by staying hydrated, using salivary substitutes, and maintaining excellent dental hygiene.
         4. Trismus: Surgery and radiation can cause difficulty opening your mouth, called trismus. This can interfere with dental care and with eating. Ask your doctor about ways to improve your mouth opening, such as stretching exercises.
      3. Osteoradionecrosis (ORN): Patients who undergo radiation are at risk for bone infection of the jaw, spine or skull. This is called osteoradionecrosis (ORN) and may cause pain, ulcerations, exposed bone, and chronic infection.
         1. ORN is diagnosed with history, examination and imaging.
         2. Treatment may involve medications, hyperbaric oxygen treatments, or in advanced cases, bone removal and reconstruction.
         3. ORN of the spine after radiation for nasopharynx cancer is a serious condition. You should tell your doctor if you experience neck pain or any new weakness or numbness.
      4. Thyroid function testing: If you have had radiation therapy, you have an increased risk of low thyroid function, or ‘hypothyroidism’. Symptoms of hypothyroidism may include fatigue, weight gain, constipation and depression. Your thyroid function should be tested every 6-12 months to determine whether you need treatment with thyroid hormone supplementation.
      5. Tobacco use:
         1. Most head and neck cancers are associated with tobacco use, especially smoking cigarettes.
         2. Continued tobacco use after treatment is associated with worse survival and higher risk of other cancers, among many other negative health effects.
         3. Quitting tobacco at any time will improve your overall health and chances of survival from head and neck cancer.
         4. If you still use tobacco after head and neck cancer treatment, we strongly encourage you to consider quitting. Your doctor can help you find resources, including medications and counseling programs, that have been proven to help.
      6. Lymphedema: Lymphedema is swelling of the soft tissue that is common for patients who have had surgery and/or radiation. Specialized Physical Therapy called Lymphedema Therapy, including massage, compression garments, exercises and skin care, is available and can significantly improve lymphedema.
      7. Shoulder dysfunction: Many head and neck cancer survivors have shoulder dysfunction, including decreased range of motion, weakness and stiffness as a result of surgery and/or radiation. Physical therapy is very helpful in improving shoulder function. If you have problems with your shoulder, ask your doctor about a referral to a physical therapist.
      8. Obstructive sleep apnea: Survivors of head and neck cancer treatment are at risk for obstructive sleep apnea (OSA) because of changes to the upper airway anatomy. Symptoms may include daytime sleepiness, snoring, gasping or choking during sleep, daytime headaches, and irritability. OSA is diagnosed with a sleep study, and there are several options for treatment. Discuss your risk of OSA with your doctor, to decide whether you should have a sleep study.
      9. Carotid artery stenosis evaluation: Radiation therapy to the neck increases the risk of carotid artery narrowing (stenosis) later in life. Carotid artery stenosis increases the risk of stroke. If you have had radiation to your neck, ask your doctor about an ultrasound to look for carotid artery stenosis.
      10. Mental and sexual health: Head and neck cancer and its treatment can result in cognitive dysfunction, anxiety, depression, body image concerns, and changes in sexual function and desire. If you suffer from any of these, you are not alone. Ask your doctor about meeting with a mental health professional to determine whether counseling and/or medication may be helpful for you.
      11. Hearing evaluation: Head and neck cancer treatments, especially with certain chemotherapy drugs, can cause hearing loss. If you have decreased hearing, you should have a hearing test to evaluate your hearing and determine whether you may benefit from hearing augmentation, such as with a hearing aid.
   3. Questions for your doctor
      1. Before/during treatment:
         1. What types of treatment are recommended (such as surgery, radiation, and/or chemotherapy)?
         2. Are there any other treatment options that I should learn about, such as clinical trials?
         3. Should I see a dentist before treatment begins?
         4. How long will treatment take? How long will it take to fully recover after treatment?
         5. What are the risks and side effects of each part of treatment? Which side effects are temporary, and which might be permanent?
         6. Will I need a feeding tube or a breathing tube (tracheostomy)? Will they be temporary or permanent?
         7. What will my swallowing, speech and breathing be like after treatment?
         8. Will I have any other functional problems after treatment?
         9. Will I be able to keep doing my job after I’ve recovered?
      2. After treatment:
         1. Should I have any imaging studies?
         2. Should I have a blood test for EBV?
         3. When should my next follow-up appointment be, and with whom?
         4. Should I have my thyroid function tested?
         5. Should I be referred to a speech and language pathologist (SLP), and or to a physical or occupational therapist?
         6. Am I receiving appropriate dental care?
         7. Should I have a sleep study?
         8. Do I need a carotid artery ultrasound?
         9. Should I have a hearing test?

 

4. Hypopharynx
   1. Anatomy
      1. The hypopharynx is the lowest portion of the throat. The hypopharynx funnels food and water into the esophagus. Air in the hypopharynx is diverted to the front, through the larynx, or voicebox, just in front of the hypopharynx.
      2. The hypopharynx is intimately related to the larynx. In fact, distinguishing larynx and hypopharynx may be difficult if a cancer involves overlapping sites. Fortunately, the treatments are often very similar.

• Squamous cells make up the lining, also known as the mucosa, of the hypopharynx. That is why squamous cell carcinoma is the most common type of hypopharynx cancer.

1. Risk Factors
   1. Hypopharyngeal tumors are more common in males
   2. Alcohol use has been found to increase the risk of cancers of the hypopharynx

• Nutritional factors that predispose to this cancer include Plummer Vinson Syndrome

1. Chronic acid reflux (GERD)
2. Occupational exposures
   1. Asbestos, wood dust, welding fumes, nickel, leather, and polycyclic aromatic hydrocarbons
3. Human Papilloma Virus (HPV)

1. Symptoms
   1. Difficulty swallowing, pain with swallowing, sore throat, ear pain, and weight loss
   2. Some patients may present with a neck mass

• Some patients may have hoarseness, or change in voice, and difficulty breathing

1. Diagnosis
   1. Diagnosis of a cancer within the hypopharynx can be challenging due to the difficulty with visualizing this area of the throat. This sometimes results in delays in diagnosis. Once a lesion is suspected, a biopsy will be required to confirm the diagnosis. This can occasionally be accomplished in the clinic with specialized equipment. To effectively biopsy and evaluate the extent of the hypopharyngeal cancer, you may require biopsy under general anesthesia in the ambulatory outpatient setting. Prior to scheduling your biopsy under general anesthesia, a complete head and neck exam including in-office fiberoptic camera exam may be performed. Patients presenting with a neck, mass may undergo a needle biopsy in the office, with or without radiologic image guidance.
   2. Your doctor may also order a variety of medical imaging:
      1. Computerized tomogram imaging (CT scan)
      2. Magnetic resonance imaging (MRI)
      3. Positron emission tomography (PET)

These images will help to further delineate the extent of the cancer. Different types of imaging help to visualize different anatomic structures Intravenous contrast enhanced CT scan and MRI can identify abnormalities in the throat or neck that suggest a primary tumor or lymph node metastases. PET imaging is a special technology that identifies a glucose (sugar) molecule being absorbed by the cancer cells and help determine whether the tumor has spread to other parts of the body. CT scan imaging of the chest may be required to visualize any spread of disease to the lungs.

1. Staging
   1. The American Joint Committee on Cancer (AJCC) has developed a staging system (TNM staging) to help guide treatment. The staging system groups cancers into stages based on their anatomic extent. The staging helps to determine the optimal treatment for a specific cancer, and provides information about expected survival rates.
   2. The staging system includes information about the extent of the original or local tumor (T classification or primary tumor extent), spread to lymph nodes (N-classification or nodal metastases), and spread to distant parts of the body (M classification or distant metastases). Combinations of T, N and M-classifications produce an overall stage. There are four stages (Stage 1-4) reported with increasing disease burden and potentially worse survival as the AJCC overall stage number increases. Factors that play a role in overall stage include: destruction of adjacent structures (ie. voice box or larynx, esophagus, involvement of the paraspinal musculature and spine and blood vessels of the neck), appearance of the cancer cells under microscopic examination by the pathologist and involvement of lymph nodes within the neck.

• Lymph nodes are small oval shaped structures found within the fat of the neck that harbor specialized immune cells that filter and fight infection and disease. Cancer cells from the hypopharynx detach from the primary and travel through lymphatic vessels to become trapped within the individual nodes. Once an oral cancer spreads to lymph nodes, it is considered more advanced, and is considered overall stage 3 or higher. In addition, the number of abnormal lymph nodes and their size is important. Sometimes, the cancer in a lymph node grows out of the lymph node, a property known as extranodal extension (ENE). Particular attention is given to identifying extranodal extension (ENE) which is defined as cancer that has breached the outside capsule of the involved lymph node. The presence of ENE suggests the cancer is a “bad actor” and treatment should be intensified.

 

Primary Tumor Stage: Hypopharynx
Stage	Description
Tx	Primary tumor cannot be assessed
Tis	Carcinoma in situ
T1	Tumor limited to one subsite of the hypopharynx; and/or, Tumor 2 cm or smaller
T2	Tumor invades more than one subsite of hypopharynx or an adjacent site; or, Tumor larger than 2 cm but not larger than 4 cm
T3	Tumor larger than 4 cm; or, Fixation of the hemilarynx; or, Extension to esophageal mucosa
T4a	Tumor invades thyroid or cricoid cartilage, hyoid bone, thyroid gland, esophageal muscle, or central compartment soft tissue
T4b	Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures

 

Regional Nodal Stage: Hypopharynx
Clinical Stage	Description
Nx	Regional lymph nodes cannot be assessed
N0	No regional lymph node metastasis
N1	Metastasis in a single ipsilateral node, 3 cm or smaller and ENE (-)
N2a	A single ipsilateral node larger than 3 cm but not larger than 6 cm and ENE (-)
N2b	Metastases in multiple ipsilateral lymph nodes, none larger than 6 cm and ENE (-)
N2c	Metastasis in bilateral or contralateral lymph nodes, none larger than 6 cm and ENE (-)
N3a	Metastasis in a lymph node larger than 6 cm and ENE (-)
N3b	Metastasis in any nodes and ENE (+)

 

 

Regional Nodal Stage: Hypopharynx
Pathologic Stage	Description
Nx	Regional lymph nodes cannot be assessed
N0	No regional lymph node metastasis
N1	Metastasis in a single ipsilateral node, 3 cm or smaller and ENE (-)
N2a	Metastasis in a single ipsilateral node 3 cm or less and ENE (+); or, A single ipsilateral node larger than 3 cm but not larger than 6 cm and ENE (-)
N2b	Metastases in multiple ipsilateral lymph nodes, none larger than 6 cm and ENE (-)
N2c	Metastasis in bilateral or contralateral lymph nodes, none larger than 6 cm and ENE (-)
N3a	Metastasis in a lymph node larger than 6 cm and ENE (-)
N3b	Metastasis in a single ipsilateral node larger than 3 cm and ENE (+); or, Multiple ipsilateral, contralateral or bilateral nodes, any with ENE (+); or, A single contralateral node any size and ENE (+)

 

AJCC Prognostic Stage Groups: Hypopharynx
Pathologic Stage	Description
0	TisN0M0
I	T1N0M0
II	T2N0M0
III	T3N0M0, T1-3N1M0
IVA	T4aN0-1M0, T1-4aN2M0
IVB	Any T, N3, M0; or, T4b, any N, M0
IVC	Any T, any N, and M1

 

1. Treatment
   1. Cancers of the hypopharynx can be treated in a variety of ways. The type of treatment your doctor feels is best is based on the location of the tumor within the hypopharynx and its size, spread to any lymph nodes or other tissues in the neck, the overall stage of your tumor, and the impact those treatments may have on your voice, swallowing and breathing.  Combined radiation and chemotherapy, or surgery followed by radiation are the two most commonly employed treatments. Surgery to remove hypopharyngeal cancers is typically called a pharyngectomy (removal of a part of the throat known as the pharynx) or laryngopharyngectomy (removal of both the voice box and the part of the throat known as the pharynx).  At the time of surgery, lymph nodes are frequently also removed, through a procedure called a neck dissection. Reconstructive surgery to the pharynx may be required depending on the amount of tissue that needs to be removed.
   2. Chemotherapy or immunotherapies are used to treat advanced or recurrent hypopharyngeal cancers. Some institutions offer clinical trials to treat advanced or incurable cases.
2. Survival
   1. Patients with cancer of the hypopharynx have a 5 year survival rate of approximately 30-50%. Those with earlier staged tumors and no spread outside of the neck have better survival rates. Delays in diagnosis and treatment contribute to poorer survival. Approximately 50% of patients treated for hypopharynx cancers will have a return of their cancer within the first year after their diagnosis.  Your doctors will watch closely for signs of recurrence or spread of disease elsewhere.
   2. Treatment of cancers of the hypopharynx may affect swallowing, breathing and speaking. Maintaining good nutrition through treatment is very important and your doctor may recommend placement of a feeding tube.  Some patients may require a temporary tracheostomy tube in the neck to help them breathe.  Others may have permanent changes in the way they breathe.  If radiation is part of your treatment plan you may experience side effects such as dry mouth, skin changes, and neck swelling.  Your doctor may recommend consultations with speech, physical and occupational therapists, and dietitians to help with your side effects during and after treatment.
3. Surveillance/Survivorship
   1. Surveillance: As with any cancer, there is a risk that hypopharynx cancer will come back (‘recur’) after treatment. ‘Surveillance’ means that your doctor(s) will monitor you after treatment with a combination of physical examination and imaging studies in order to detect disease that has recurred. Protocol details will vary from institution to institution. Surveillance typically lasts for at least 5 years. Once cleared by the treating physician, patients may transition into a cancer surveillance/survivorship clinic, often run by an advanced practice provider (APP) that is well trained in head and neck cancer surveillance.
      1. Physical examination: Your doctor(s) will examine you according to the following schedule:
         1. Year One: every 1-3 months
         2. Year Two: every 2-6 months
         3. Years Three through 5: every 4-8 months
         4. After 5 years: every 12 months or as needed
      2. Imaging: The timing and type of imaging you have will be based on your doctor’s judgment.
         1. Baseline imaging within 6 months of completing treatment may be recommended.
         2. Imaging may include CT scans, PET/CT scans, MRI, or sometimes ultrasound.
         3. Additional imaging will be based on your symptoms, exam, and your doctor’s judgment.
         4. It is important to let your doctor know if you feel a new persistent pain or neck mass or if you feel that you are having more trouble swallowing.

 

1. Survivorship: Hypopharynx cancer and its treatment can affect many areas of your health and quality of life. ‘Survivorship’ refers to caring for your health and well-being from the moment you receive your diagnosis, and for the rest of your life. Depending what your treatment involves, important parts of survivorship for hypopharynx cancer may include:
   1. Speech and swallowing evaluation and therapy: This is typically with a Speech-Language Pathologist, or SLP, with expertise in speech and swallowing for head and neck cancer patients.
      1. Swallowing: Safe swallowing is important for your health and quality of life. Poor swallowing function, called ‘dysphagia’, can lead to health problems such as pneumonia or malnutrition, and may lead to the need for a feeding tube in order to stay healthy. You may also be referred to a dietician for guidance on how to maintain a nutritious diet even if you have dysphagia.
      2. Esophageal stricture: You may be at risk for narrowing of your esophagus, called an ‘esophageal stricture’. This can be diagnosed with a swallowing testing. Some patients have improvements in their swallowing once their esophageal stricture is stretched.
      3. Speech: Rehabilitation of your speaking is important for your communication and quality of life.
   2. Oral and dental health: Hypopharynx cancer and its treatment can have a major impact on your teeth, taste, saliva and jaw bone.
      1. Dental cleaning and care: Hypopharynx cancer patients should establish care early after diagnosis, ideally before treatment, with a dentist who has experience in head and neck cancer. Some dental work may be necessary prior to treatment. In the long term, patients should have routine cleaning and examination. Routine fluoride treatments may be recommended.
      2. Radiation and dental health: Radiation can be detrimental to your dental health. It is especially important for patients who undergo radiation to have regular dental care and excellent dental hygiene.
      3. Dry mouth: Dry mouth, or ‘xerostomia’, is common after radiation therapy and can have a significant negative impact on quality of life. There is no cure for xerostomia. If you have xerostomia, you can decrease the symptoms by staying hydrated, using salivary substitutes, and maintaining excellent dental hygiene.
      4. Chondronecrosis of the larynx: Patients who undergo radiation are at risk for damage to the larynx or voicebox, which is located just in front of the hypopharynx. The cartilage of the larynx which preserves the structural integrity of the voicebox becomes severely damaged and dysfunctional. The larynx no longer separates breathing and swallowing functions. Saliva and foods go into the breathing passages, causing coughing, choking and pneumonia. Patients may not be able to take their nutrition by mouth, due to the severity of the swallowing problem. In severe cases, they may require surgical removal of a dysfunctional larynx which is causing life threatening pneumonias due to aspiration.
   3. Thyroid function testing: If you have had radiation therapy or surgery for hypopharynx cancer, you have an increased risk of low thyroid function, or ‘hypothyroidism’. Symptoms of hypothyroidism may include fatigue, weight gain, constipation and depression. Your thyroid function should be tested every 6-12 months to determine whether you need treatment with thyroid hormone supplementation.
   4. Tobacco use:
      1. Most head and neck cancers are associated with tobacco use, especially smoking cigarettes.
      2. Continued tobacco use after treatment is associated with worse survival and higher risk of other cancers, among many other negative health effects.
      3. Quitting tobacco at any time will improve your overall health and chances of survival from head and neck cancer.
      4. If you still use tobacco after head and neck cancer treatment, we strongly encourage you to consider quitting. Your doctor can help you find resources, including medications and counseling programs, that have been proven to help.
   5. Lymphedema: Lymphedema is swelling of the soft tissue that is common for patients who have had surgery and/or radiation. Specialized Physical Therapy called Lymphedema Therapy, including massage, compression garments, exercises and skin care, is available and can significantly improve lymphedema.
   6. Shoulder dysfunction: Many head and neck cancer survivors have shoulder dysfunction, including decreased range of motion, weakness and stiffness as a result of surgery and/or radiation. Physical therapy is very helpful in improving shoulder function. If you have problems with your shoulder, ask your doctor about a referral to a physical therapist.
   7. Obstructive sleep apnea: Survivors of head and neck cancer treatment are at risk for obstructive sleep apnea (OSA) because of changes to the upper airway anatomy. Symptoms may include daytime sleepiness, snoring, gasping or choking during sleep, daytime headaches, and irritability. OSA is diagnosed with a sleep study, and there are several options for treatment. Discuss your risk of OSA with your doctor, to decide whether you should have a sleep study.
   8. Carotid artery stenosis evaluation: Radiation therapy to the neck increases the risk of carotid artery narrowing (stenosis) later in life. Carotid artery stenosis increases the risk of stroke. If you have had radiation to your neck, ask your doctor about an ultrasound to look for carotid artery stenosis.
   9. Mental and sexual health: Head and neck cancer and its treatment can result in cognitive dysfunction, anxiety, depression, body image concerns, and changes in sexual function and desire. If you suffer from any of these, you are not alone. Ask your doctor about meeting with a mental health professional to determine whether counseling and/or medication may be helpful for you.
   10. Hearing evaluation: Head and neck cancer treatments, especially with certain chemotherapy drugs, can cause hearing loss. If you have decreased hearing, you should have a hearing test to evaluate your hearing and determine whether you may benefit from hearing augmentation, such as with a hearing aid.
2. Questions for your doctor
   1. Before/during treatment:
      1. What types of treatment are recommended (such as surgery, radiation, and/or chemotherapy)?
      2. Are there any other treatment options that I should learn about, such as clinical trials?
      3. Should I see a dentist before treatment begins?
      4. How long will treatment take? How long will it take to fully recover after treatment?
      5. What are the risks and side effects of each part of treatment? Which side effects are temporary, and which might be permanent?
      6. Will I need a feeding tube or a breathing tube (tracheostomy)? Will they be temporary or permanent?
      7. What will my swallowing, speech and breathing be like after treatment?
      8. Will I have any other functional problems after treatment?
      9. Will I be able to keep doing my job after I’ve recovered?
   2. After treatment:
      1. Should I have any imaging studies?
      2. When should my next follow-up appointment be, and with whom?
      3. Should I have my thyroid function tested?
      4. Should I be referred to a speech and language pathologist (SLP), and or to a physical or occupational therapist?
      5. Am I receiving appropriate dental care?
      6. Should I have a sleep study?
      7. Do I need a carotid artery ultrasound?
      8. Should I have a hearing test?

 

 

5. Larynx
   1. Anatomy
      1. The larynx, or voice box, is composed of cartilage, muscle and a mucosal lining. The cartilage skeleton can be seen and felt externally and is often referred to as the “Adam’s Apple.” These structures serve to create your voice but the main function of the larynx is to protect the lungs from aspiration (food and water entering the lungs). Internally, the larynx contains vocal cords and the epiglottis. The epiglottis is a flap of cartilage that folds over the larynx while swallowing to protect the airway from aspiration. The epiglottis stays open during breathing so air can pass easily.
      2. Involvement of these important anatomical structures by cancer causes voice changes and difficulty swallowing.

• The hypopharynx is intimately related to the larynx. In fact, distinguishing larynx and hypopharynx may be difficult if a cancer involves overlapping sites. Fortunately, the treatments are often very similar.

 

1. Squamous cells make up the lining, also known as the mucosa, of the larynx. That is why squamous cell carcinoma is the most common type of larynx cancer.

 

 

 

 

1. Risk Factors
   1. Tobacco use is the most common risk factor associated with cancer of the larynx
      1. Alcohol can have an additive effect
   2. Occupational exposures
      1. Sulfuric acid
   3. Symptoms
      1. Hoarseness, chronic sore throat, ear pain, pain with swallowing, difficulty swallowing, difficulty breathing, chronic cough, weight loss, and coughing up blood
   4. Diagnosis
      1. Diagnosis of a cancer within the larynx (voice box) is often first suspected with patients reporting voice changes, coughing up blood or swallowing difficulties. Once an abnormality is observed, a biopsy will be required to confirm the diagnosis. This can occasionally be accomplished in the clinic with specialized equipment. To effectively biopsy and evaluate the extent of the laryngeal cancer, you may require biopsy under general anesthesia in the ambulatory outpatient setting. Prior to scheduling your biopsy under general anesthesia, a complete head and neck exam including in-office fiberoptic camera exam to visualize the tumor growth and palpation of neck lymph nodes will be performed. Patients presenting with a neck, mass may undergo a needle biopsy in the office setting or under radiologic image guidance.
      2. Your doctor may also order a variety of medical imaging:
         1. Computerized tomogram imaging (CT scan)
         2. Magnetic resonance imaging (MRI)
         3. Positron emission tomography (PET)

 

These images will help to further delineate the extent of the cancer. Different types of imaging help to visualize different anatomic structures Intravenous contrast enhanced CT scan and MRI can identify abnormalities in the larynx or neck that suggest a primary tumor or lymph node metastases. PET imaging is a special technology that identifies a glucose (sugar) molecule being absorbed by the cancer cells and help localize the tumor in other parts of the body. CT scan imaging of the chest may be required to visualize any spread of disease to the lungs.

1. Staging
   1. The American Joint Committee on Cancer (AJCC) has created a staging system (TNM staging)
   2. to help guide treatment. The staging system groups cancers into stages based on their anatomic extent. The staging helps to determine the optimal treatment for a specific cancer, and provides information about expected survival rates.

• The staging system includes information about the extent of the original or local tumor (T classification or primary tumor extent), spread to lymph nodes (N-classification or nodal metastases), and spread to distant parts of the body (M classification or distant metastases). The T staging system is further refined into three subsites (supraglottis, glottis, subglottis) based upon its location relative to the vocal cords (glottis). More advanced tumors impair normal movement of the vocal cords, or involve multiple subsites within the larynx.

1. Combinations of T, N and M-classifications produce an overall stage. There are 4 overall staging groups (Stage 1-4). As the AJCC TNM stage number increases so does the disease burden. More advanced cancers lead to worse survival rates. Factors that play a role in the overall stage include: destruction of nearby structures (ie. tongue base, extralaryngeal invasion, thyroid cartilage destruction, involvement of the paraspinal musculature or esophagus and blood vessels of the neck) and involvement of lymph nodes within the neck.
2. Lymph nodes are small oval shaped structures found within the fat of the neck that harbor immune cells that filter and fight infection and disease.. Cancer cells from the larynx detach from the primary tumor, and travel through lymphatic vessels becoming trapped in lymph nodes where they start to grow. Once a larynx cancer spreads to lymph nodes, it is considered more advanced, and is considered overall stage 3 or higher. In addition, the number of abnormal lymph nodes and their size is important. Sometimes, the cancer in a lymph node grows out of the lymph node, a property known as extranodal extension (ENE). Extranodal extension (ENE) is defined as cancer that has breached the outside capsule of the involved lymph node. In general, the demonstration of ENE suggests a cancer is aggressive, and intensification of treatment should be considered.

 

Primary Tumor Stage: Supraglottic Larynx
Stage	Description
Tx	Primary tumor cannot be assessed
Tis	Carcinoma in situ
T1	Tumor limited to one subsite of the supraglottis with normal vocal cord mobility
T2	Tumor invades more than one subsite of supraglottis or glottis or an adjacent site without fixation of the larynx
T3	Tumor limited to the larynx with vocal cord fixation; and/or, Invasion of any of the following: postcricoid, preepiglottic space, paraglottic space, or inner cortex of thyroid cartilage
T4a	Tumor invades through outer cortex of thyroid cartilage; and/or,  invades tissues beyond the larynx
T4b	Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures

 

 

Primary Tumor Stage: Glottic Larynx
Stage	Description
Tx	Primary tumor cannot be assessed
Tis	Carcinoma in situ
T1a	Tumor limited to one vocal cord
T1b	Tumor involves both vocal cords
T2	Tumor extends to supraglottis and/or subglottis with normal or impaired mobility
T3	Tumor limited to the larynx with vocal cord fixation; and/or, Invasion of paraglottic space and/or inner cortex of thyroid cartilage
T4a	Tumor invades through outer cortex of thyroid cartilage; and/or,  invades tissues beyond the larynx
T4b	Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures

 

Primary Tumor Stage: Subglottic Larynx
Stage	Description
Tx	Primary tumor cannot be assessed
Tis	Carcinoma in situ
T1	Tumor limited to the subglottis
T2	Tumor extends to vocal cords with normal or impaired mobility
T3	Tumor limited to the larynx with vocal cord fixation; and/or, Invasion of paraglottic space and/or inner cortex of thyroid cartilage
T4a	Tumor invades through outer cortex of thyroid cartilage; and/or,  invades tissues beyond the larynx
T4b	Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures

 

 

Regional Nodal Stage: Larynx
Clinical Stage	Description
Nx	Regional lymph nodes cannot be assessed
N0	No regional lymph node metastasis
N1	Metastasis in a single ipsilateral node, 3 cm or smaller and ENE (-)
N2a	A single ipsilateral node larger than 3 cm but not larger than 6 cm and ENE (-)
N2b	Metastases in multiple ipsilateral lymph nodes, none larger than 6 cm and ENE (-)
N2c	Metastasis in bilateral or contralateral lymph nodes, none larger than 6 cm and ENE (-)
N3a	Metastasis in a lymph node larger than 6 cm and ENE (-)
N3b	Metastasis in any nodes and ENE (+)

 

 

Regional Nodal Stage: Larynx
Pathologic Stage	Description
Nx	Regional lymph nodes cannot be assessed
N0	No regional lymph node metastasis
N1	Metastasis in a single ipsilateral node, 3 cm or smaller and ENE (-)
N2a	Metastasis in a single ipsilateral node 3 cm or less and ENE (+); or, A single ipsilateral node larger than 3 cm but not larger than 6 cm and ENE (-)
N2b	Metastases in multiple ipsilateral lymph nodes, none larger than 6 cm and ENE (-)
N2c	Metastasis in bilateral or contralateral lymph nodes, none larger than 6 cm and ENE (-)
N3a	Metastasis in a lymph node larger than 6 cm and ENE (-)
N3b	Metastasis in a single ipsilateral node larger than 3 cm and ENE (+); or, Multiple ipsilateral, contralateral or bilateral nodes, any with ENE (+); or, A single contralateral node any size and ENE (+)

 

AJCC Prognostic Stage Groups: Larynx
Pathologic Stage	Description
0	TisN0M0
I	T1N0M0
II	T2N0M0
III	T3N0M0, T1-3N1M0
IVA	T4aN0-1M0, T1-4aN2M0
IVB	Any T, N3, M0; or, T4b, any N, M0
IVC	Any T, any N, and M1

 

 

1. Treatment
   1. Fortunately, there are several effective treatment options for larynx cancer. Treatment selection typically depends on the exact location of the tumor, the stage of the tumor and how well the larynx is functioning.
   2. Early Stage Larynx Cancer (Stages 1 & 2)
      1. Early stage larynx cancer is typically treated with either surgery or radiation. Larynx preservation, without the need for a total laryngectomy is the rule. Occasionally, both treatment types may be required.
      2. Surgical removal of larynx cancer through the mouth is possible for some early larynx cancers. Transoral laser microsurgery (TLM) is an effective tool for early larynx cancers. Transoral robotic surgery may be considered. External neck incisions are not required for removal of the larynx cancer; however, incisions are needed to remove lymph nodes in the neck. Not every patient is a candidate for TLM. Patients must meet specific criteria that ensure the best results. Potential risks of TLM include injury to the teeth and gums, injury to the trachea or esophagus, airway fire, bleeding, swallowing difficulties and hoarse voice. These surgeries are highly specialized, and consultation with a surgeon with a vast experience should be considered.
      3. Removal of part of the larynx may be considered in selected early stage cancers. These operations are chosen for patients with slightly larger tumors and inadequate access to the tumor through the mouth. These operations are known as open partial laryngectomy. The portion of the larynx with the cancer is removed through an incision in the neck. A temporary tracheostomy and feeding tube are often required, and voice quality and swallowing function are not as favorable as with transoral approaches. However, the operation achieves high success rates in properly selected patients, and may be preferred to a total laryngectomy.
      4. Laryngectomy is more commonly needed for advanced larynx cancers but is occasionally necessary for early stage tumors in certain locations or early tumors in patients who have failed other treatments. Laryngectomy requires complete removal of the voice box, which is not reversible. Patients who undergo a laryngectomy will have a permanent stoma or opening in the neck for breathing. Most patients are eventually able to maintain their nutrition by mouth without a feeding tube.
      5. Radiation therapy is a common and effective tool for treating early larynx cancers. Typically, treatments are given every day, five days per week, for up to 7 weeks. A customized mask is created for patients prior to treatment to target the radiation. Side effects of radiation treatment include red/sore skin, sore throat, oral sores, voice box swelling, and difficulty with swallowing.
      6. Chemotherapy, which is a broad term for intravenous or orally administered anti-cancer medications, is typically reserved for advanced laryngeal cancers. Immunotherapy, a newer class of medications that takes advantage of the immune properties of tumors, is typically reserved for patients with incurable larynx cancer.

• Advanced Stage Laryngeal Cancer (Stages 3 & 4)

1. Advanced stage larynx cancers are typically treated with at least two treatments (surgery and radiation or radiation and chemotherapy). Usually, minimally invasive surgical techniques such as TLM and robotic surgery are not recommended in advanced stage cancers.
2. Radiation and chemotherapy are often used as part of what is referred to as an “organ preservation” approach. The goal of the treatment is to cure the cancer while anatomically preserving the larynx. Laryngeal functions include breathing, speech, and swallowing food and liquids safely. Patients with advanced larynx cancers may have a poorly functioning larynx as a result of the tumor-related destruction of the larynx. When a larynx is not functioning properly to separate breathing and swallowing  functions, it is considered a “non-functioning larynx.” The patient may require a tracheostomy to breathe and a feeding tube to eat. They are unlikely to regaining normal function with organ preservation approaches. Removal of the diseased organ surgically is usually recommended in a surgery known as a total laryngectomy which results in a permanent opening or tracheostoma in the neck. In this operation, the windpipe is permanently attached to an opening in the skin, and the throat is attached to the esophagus. Breathing and swallowing functions are permanently surgically separated. While laryngectomy leaves the patient with a permanent stoma (hole) in the neck, most patients are able to eat and rehabilitate their communication. As patients are not able to use their own voice, patients may eventually use a tracheoesophageal puncture device (TEP), electrolarynx or text-to-talk devices to communicate.
3. Reconstructive surgery is sometimes required during laryngectomy surgery. Tissue used for reconstruction can come from the chest wall, shoulder, wrist, thigh or other location depending on the tumor location and the individual surgeon’s preferences.

• Once surgery is complete, the final pathology result will direct what additional treatments may be required. Most patients with advanced larynx cancer undergoing surgery who have not had radiation before will require post-operative radiation therapy. Post-operative chemotherapy is also sometimes recommended in combination with radiation therapy for very advanced cases.
• Organ preservation with chemoradiation: For many patients with advanced larynx cancer, non-surgical treatment with radiation and chemotherapy without surgery may be good option. These treatments are usually combined, with patients receiving chemotherapy infusions once per week while also undergoing daily radiation treatments. The most common chemotherapy drugs administered are cisplatin or carboplatin. Radiation plus chemotherapy can be quite effective for many advanced larynx cancers, and many patients may be able to avoid a laryngectomy. Side effects can include sore throat, sore mouth, trouble swallowing, weight loss, kidney disfunction, nerve damage, hearing loss, skin irritation, voice box swelling and fatigue.

1. If the larynx cancer is determined to be incurable to due metastases or involvement of vital unresectable structures, chemotherapy alone and/or immunotherapy may be administered. Typically, these treatments are meant to minimize symptoms and slow tumor progression rather than cure the disease.

1. Survival
   1. Survival from laryngeal cancer are directly related to the cancer stage. Early stage cancers tend to respond better to treatment than later stage cancers. Delays in diagnosis and treatment may contribute to poorer outcomes. Staging differs based on which part of the larynx is affected, but typically, smaller tumors that involve just one or two components of the larynx, and have not spread to lymph nodes are classified as Stage I or Stage II cancers. Larger tumors that begin to grow into the major cartilages of the larynx or that causes one of the vocal cords to be paralyzed are Stage III cancers. Tumors that grow outside of the larynx are Stage IV cancers. If you have a cancer that has spread to lymph nodes in the neck, the cancer is automatically Stage III or higher, no matter the size of the tumor in the larynx. According to the American Cancer Society, Stage I and II cancers have a 5-year survival of 60-83%, depending on the location of the tumor in the larynx. When the cancer has spread to lymph nodes in the neck (Stage III), the 5-year survival is around 50%. Stage IV laryngeal cancers typically carry of 5-year survival of less than 50%.
   2. Your physician will help determine what type of treatment is best based on the location of the cancer, the stage of the cancer, and the type of symptoms that you have prior to treatment (voice changes, trouble swallowing, trouble breathing, etc.).

• Early side effects of treatment depend on the type of treatments. Patients with early laryngeal cancers who are treated with surgery may expect to have some voice changes and some difficulty swallowing that improve with time and speech therapy. Depending on the procedure, patients may require a temporary tracheotomy. A tracheostomy is a tube placed into the windpipe, which allows patients to breath when there is swelling in the voice box that would otherwise make breathing difficult. When the swelling improves, the tracheotomy may be removed, and the opening in the windpipe closes. Occasionally, a temporary feeding tube (either in the stomach or in the nose) may be required if there is significantly difficulty with swallowing after surgery.

1. Patients with early cancers that are treated with radiation may have less voice changes but could still have some trouble with swallowing due to pain, throat dryness, and other side effects from radiation. Another common side effect from radiation for laryngeal cancer is lymphedema. This term refers to swelling of skin of the neck. There are specialized treatments to help improve lymphedema that are often conducted by physical therapists. As with patients who undergo surgical treatment for laryngeal cancer, some patients who are treated with radiation require temporary feeding tubes. Speech therapists can help with swallowing after treatment is completed, but some patients lose their ability to swallow, are unable to take a diet by mouth and require feeding tubes permanently.
2. For the most advanced laryngeal cancers, or for cancers that return after radiation therapy, treatment may involve complete removal of the voice box as mentioned above. Patients who undergo total laryngectomy are permanent neck breathers and no longer have a voice box with which to talk. In many cases, laryngectomy patients are able to swallow normally. There are also several ways for laryngectomy patients to learn how to speak after having the voice box removed, including use of an electrolarynx, esophageal speech, or having a trachea-esophageal prosthesis placed. Specialized speech therapists train laryngectomy patients in each of these types of speech replacements, depending on what the patient capabilities and preference after completing treatment. Some patients with TEP speech rehabilitation have near normal voices, but TEP speech requires motivation to pick up a new skill.

 

1. Surveillance/Survivorship
   1. Surveillance: As with any cancer, there is a risk that larynx cancer will come back (‘recur’) after treatment. ‘Surveillance’ means that your doctor(s) will monitor you after treatment with a combination of physical examination and imaging studies in order to detect disease that has recurred. Protocol details will vary from institution to institution. Patients will be followed for at least 5 years once completing your cancer treatment. Once cleared by the treating physician, patients may transition into a cancer surveillance/survivorship clinic, often run by an advanced practice provider (APP) that is well trained in head and neck cancer surveillance.
      1. Physical examination: Your doctor(s) will examine you according to the following schedule:
         1. Year One: every 1-3 months
         2. Year Two: every 2-6 months
         3. Years Three through 5: every 4-8 months
         4. After 5 years: every 12 months or as needed.
      2. Imaging: The timing and type of imaging you have will be based on your doctor’s judgment.
         1. Baseline imaging within 6 months of completing treatment.
         2. Imaging may include CT scans, PET/CT scans, MRI, or sometimes ultrasound.
         3. Additional imaging will be based on your symptoms, exam, and your doctor’s judgment.
      3. Survivorship: Larynx cancer and its treatment can affect many areas of your health and quality of life. ‘Survivorship’ refers to caring for your health and well-being from the moment you receive your diagnosis, and for the rest of your life. Depending what your treatment involves, important parts of survivorship for larynx cancer may include:
         1. Speech and swallowing evaluation and therapy: This is typically with a Speech-Language Pathologist, or SLP, with expertise in speech and swallowing for head and neck cancer patients.
            1. Swallowing: Safe swallowing is important for your health and quality of life. Poor swallowing function, called ‘dysphagia’, can lead to health problems such as pneumonia or malnutrition, and may lead to the need for a feeding tube for nutrition. You may also be referred to a dietician for guidance on how to maintain adequate nutrition.
            2. Esophageal stricture: You may be at risk for narrowing of your esophagus, called an ‘esophageal stricture’. This can be diagnosed with a swallowing X-ray. Some patients benefit from having their esophageal stricture stretched.
            3. Speech: Rehabilitation of your speaking is important for your communication and quality of life. If you have had a total laryngectomy, a SLP specialist can help you learn about options for voice rehabilitation.
         2. Oral and dental health: Larynx cancer and its treatment can have a major impact on your teeth, taste, saliva and jaw bone.
            1. Dental cleaning and care: Larynx cancer patients should establish care early after diagnosis, ideally before treatment, with a dentist who has experience in head and neck cancer. Some dental work may be necessary prior to treatment. In the long term, patients should have routine cleaning and examination. Routine fluoride treatments may be recommended.
            2. Radiation and dental health: Radiation can be detrimental to your dental health. It is especially important for patients who undergo radiation to have regular dental care and excellent dental hygiene.
            3. Dry mouth: Dry mouth, or ‘xerostomia’, is common after radiation therapy and can have a significant negative impact on quality of life. There is no cure for xerostomia. If you have xerostomia, you can decrease the symptoms by staying hydrated, using salivary substitutes, and maintaining excellent dental hygiene.
            4. Chondronecrosis of the larynx: Patients who undergo radiation are at risk for damage to the larynx or voicebox. The cartilage of the larynx which preserves the structural integrity of the voicebox becomes severely damaged and dysfunctional. The larynx no longer separates breathing and swallowing functions. Saliva and foods go into the breathing passages, causing coughing, choking and pneumonia. Patients may not be able to take their nutrition by mouth, due to the severity of the swallowing problem. In severe cases, they may require surgical removal of a dysfunctional larynx which is causing life threatening pneumonias due to aspiration.
            6. Trismus: Surgery and radiation can cause difficulty opening your mouth, called trismus. This can interfere with dental care and with eating. Ask your doctor about ways to improve your mouth opening, such as stretching exercises.
         3. Thyroid function testing: If you have had radiation therapy or surgery for larynx cancer, you have an increased risk of low thyroid function, or ‘hypothyroidism’. Symptoms of hypothyroidism may include fatigue, weight gain, constipation and depression. Your thyroid function should be tested every 6-12 months to determine whether you need treatment with thyroid hormone supplementation.
         4. Tobacco use:
            1. Most head and neck cancers are associated with tobacco use, especially smoking cigarettes.
            2. Continued tobacco use after treatment is associated with worse survival and higher risk of other cancers, among many other negative health effects.
            3. It is important to know that quitting tobacco at any time will improve your overall health and chances of survival from head and neck cancer.
            4. If you still use tobacco after head and neck cancer treatment, we strongly encourage you to consider quitting. Your doctor can help you find resources, including medications and counseling programs, that have been proven to help.
         5. Lymphedema: Lymphedema is swelling of the soft tissue that is common for patients who have had surgery and/or radiation. Specialized Physical Therapy called Lymphedema Therapy provide massage, compression garments, exercises and skin care, is available and can significantly improve lymphedema.
         6. Shoulder dysfunction: Many head and neck cancer survivors have shoulder dysfunction, including decreased range of motion, weakness and stiffness as a result of surgery and/or radiation. Physical therapy is very helpful in improving shoulder function. If you have problems with your shoulder, ask your doctor about a referral to a physical therapist.
         7. Obstructive sleep apnea: Survivors of head and neck cancer treatment are at risk for obstructive sleep apnea (OSA) because of changes to the upper airway anatomy. Symptoms may include daytime sleepiness, snoring, gasping or choking during sleep, daytime headaches, and irritability. OSA is diagnosed with a sleep study, and there are several options for treatment. Discuss your risk of OSA with your doctor, to decide whether you should have a sleep study.
         8. Carotid artery stenosis evaluation: Radiation therapy to the neck increases the risk of carotid artery narrowing (stenosis) later in life. Carotid artery stenosis increases the risk of stroke. If you have had radiation to your neck, ask your doctor about an ultrasound to look for carotid artery stenosis.
         9. Mental and sexual health: Head and neck cancer and its treatment can result in cognitive dysfunction, anxiety, depression, body image concerns, and changes in sexual function and desire. If you suffer from any of these, you are not alone. Ask your doctor about meeting with a mental health professional to determine whether counseling and/or medication may be helpful for you.
         10. Hearing evaluation: Head and neck cancer treatments, especially with certain chemotherapy drugs, can cause hearing loss. If you have decreased hearing, you should have a hearing test to evaluate your hearing and determine whether you may benefit from hearing augmentation, such as with a hearing aid.
      4. Questions for your doctor
         1. Before/during treatment:
            1. What types of treatment are recommended (such as surgery, radiation, and/or chemotherapy)?
            2. Why are these treatments best (best chance of cure, best chance of swallowing function, best chance to preserve my voice)?
            3. Are there any other treatment options that I should learn about, such as clinical trials?
            4. Should I see a dentist before treatment begins?
            5. How long will treatment take? How long will it take to fully recover after treatment?
            6. What are the risks and side effects of each part of treatment? Which side effects are temporary, and which might be permanent?
            7. Will I need a feeding tube or a breathing tube (tracheostomy)? Will they be temporary or permanent?
            8. What will my swallowing, speech and breathing be like after treatment?
            9. If you are having a total laryngectomy:
               1. What are my options for voice rehabilitation?
               2. What permanent activity restrictions will I have?
            10. Will I have any other functional problems after treatment?
            11. Will I be able to keep doing my job after I’ve recovered?
         2. After treatment:
            1. Should I have any imaging studies?
            2. When should my next follow-up appointment be, and with whom?
            3. Should I have my thyroid function tested?
            4. Should I be referred to a speech and language pathologist (SLP), and or to a physical or occupational therapist?
            5. Am I receiving appropriate dental care?
            6. Should I have a sleep study?
            7. Do I need a carotid artery ultrasound?
            8. Should I have a hearing test?