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Laryngeal Cancer

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If an adult in your life has laryngeal cancer, you may want to learn more about it. This page has information about laryngeal cancer, its types and what to expect.

First, you should understand what cancer is. Cancer is a disease caused by abnormal cells that grow too rapidly. Our bodies are made of cells so tiny you need a microscope to see them. Cancer cells don’t look or act like normal cells, and they don’t allow our normal cells to work properly. There are many different types of cancer that can grow anywhere in the body.1 Muscat JE, Wynder EL. Tobacco, alcohol, asbestos, and occupational risk factors for laryngeal cancer. Cancer. May 1 1992;69(9):2244-2251.

Laryngeal cancer refers to cancer of the larynx, or voice box. It is the second most common cancer of the head and neck after mouth cancer. Because the voice box, and parts of the body near the voice box, are so important to breathing, speaking and eating, the cancer itself and the treatment used can greatly influence quality of life. Most cancers of the larynx are found after there a patient has hoarseness that doesn’t go away or difficulty with breathing or swallowing.

Understanding the anatomy

To understand laryngeal cancer, you need a basic understanding of the anatomy (parts) of the head and neck.

The larynx, or voice box, is part of the throat. It is located below the oropharynx (middle throat) and in front of the hypopharynx (lower throat).

04a_throat_overview CROP

The anatomy of the voice box can be complicated for people (including doctors) who don’t deal with this area all the time. It is located in the middle of the neck, partly protected by the thyroid cartilage (which you can feel in your neck as the Adam’s Apple).

33_front_larynx34_lateral_larynxCROP

From a cancer perspective, the larynx is divided into three subsites: the supraglottis, glottis and subglottis. Laryngeal cancer starts in one of these subsites, but it can grow into another subsite.

35_coronal_larynx36_vocal_cords

  • Supraglottis: This part of the voice box is above the vocal cords. Subsites of the supraglottis include the epiglottis above the hyoid bone, the epiglottis below the hyoid bone, the aryepiglottic folds, the arytenoids and the false vocal cords (also called the ventricular folds).
  • Glottis: This part of the voice box is hidden behind the thyroid cartilage. It is responsible for producing one’s voice. It is made up of the true vocal cords. The anterior commissure refers to the location in the front of the larynx where the vocal cords meet.
  • Subglottis: This part of the voice box extends from the bottom of the vocal cords to one centimeter below where it joins with the trachea (or windpipe).

Causes of laryngeal cancer

You may want to know what caused the laryngeal cancer. The short answer is that we don’t know. You can be sure that you did nothing to cause it. Also, it is not contagious (you can’t catch it).

In most cases it’s a combination of genetics and the environment.

By far the most common contributor to laryngeal cancer is using tobacco, particularly smoking it. Drinking too much alcohol also contributes to the risk of developing cancer of the larynx.

Risk factors that can increase the chance of getting laryngeal cancer include:

  • Tobacco: Smoking cigarettes, cigars or pipes and using chewing tobacco greatly increase the chance of getting a laryngeal cancer.1, Muscat JE, Wynder EL. Tobacco, alcohol, asbestos, and occupational risk factors for laryngeal cancer. Cancer. May 1 1992;69(9):2244-2251.2 Lewin F, Norell SE, Johansson H, et al. Smoking tobacco, oral snuff, and alcohol in the etiology of squamous cell carcinoma of the head and neck: a population-based case-referent study in Sweden. Cancer. Apr 1 1998;82(7):1367-1375.
  • Alcohol: Drinking too much alcohol is strongly linked to getting laryngeal cancer. And if one both smokes and drinks heavily, the risk more than doubles.1, Muscat JE, Wynder EL. Tobacco, alcohol, asbestos, and occupational risk factors for laryngeal cancer. Cancer. May 1 1992;69(9):2244-2251.2 Lewin F, Norell SE, Johansson H, et al. Smoking tobacco, oral snuff, and alcohol in the etiology of squamous cell carcinoma of the head and neck: a population-based case-referent study in Sweden. Cancer. Apr 1 1998;82(7):1367-1375.
  • Exposure to radiation in the past: Being exposed to radiation through previous treatment for another disease, certain working conditions or even a natural disaster can increase the chances of some laryngeal cancers.3 Lynch HT, Mulcahy GM, Harris RE, Guirgis HA, Lynch JF. Genetic and pathologic findings in a kindred with hereditary sarcoma, breast cancer, brain tumors, leukemia, lung, laryngeal, and adrenal cortical carcinoma. Cancer. May 1978;41(5):2055-2064.

Other factors associated with developing cancer of the larynx include:

  • Smoking marijuana
  • Possibly second-hand smoke
  • History of juvenile HPV infection (called recurrent respiratory papillomatosis, or RRP): This infection in children leads to recurrent warts in the airway. Children with this problem require frequent surgeries to prevent the warts from blocking the airway. Fortunately, in most cases the problem gets much less severe after puberty. Rarely, these patients can develop squamous cell carcinoma associated with the RRP.4 Katsenos S, Becker HD. Recurrent respiratory papillomatosis: a rare chronic disease, difficult to treat, with potential to lung cancer transformation: apropos of two cases and a brief literature review. Case Rep Oncol. 2011 Mar 23;4(1):162-71.
  • Exposure to metal, plastics, paint, wood dust and asbestos at work
  • Plummer-Vinson Syndrome (especially for hypopharyngeal and cervical esophageal cancer): This condition, more common in women, is associated with low iron and low blood counts (anemia), along with webs of tissues in the throat that cause difficulty with swallowing.6 NCCN Guidelines version 2.2012. Esophageal and esophagogastric junction cancers. Principles of Endoscopic Staging and Therapy. NCCN 2013.
  • Gastroesophageal reflux disease (GERD): Though GERD is not a proven cause of throat cancers, multiple studies have shown a link between “acid reflux” and throat cancer.7, El-Serag HB, Hepworth EJ, Lee P, Sonnenberg A. Gastroesophageal reflux disease is a risk factor for laryngeal and pharyngeal cancer. Am J Gastroenterol. Jul 2001;96(7):2013-8.8 Vaezi MF, Qadeer MA, Lopez R, Colabianchi N. Laryngeal cancer and gastroesophageal reflux disease: a case-control study. Am J Med. Sep 2006;119(9):768-76.

Signs and symptoms of laryngeal cancer

Most commonly, patients with cancer of the larynx will go to a doctor because they noticed a change in their voice.9 Hoare TJ, Thomson HG, Proops DW. Detection of laryngeal cancer--the case for early specialist assessment. Journal of the Royal Society of Medicine. Jul 1993;86(7):390-392. In some cases, the first sign of laryngeal cancer could be a lump in the neck. This might mean that the tumor has spread to the lymph nodes in the neck.

The most common symptoms of cancer of the larynx include:

  • A hoarse voice: The voice is made by a smooth vibration of the vocal cords at a super-fast speed. A tumor on the cords or around the muscles or joints of the vocal cords can cause the voice to change quite drastically.
  • A lump in the neck: This will be a symptom of laryngeal cancer if it has spread to lymph nodes in the neck. This can be the first symptom that brings a patient to the doctor. If there is a neck mass and there is concern that it represents cancer spread from somewhere else, the doctor will evaluate other areas, including the larynx.
  • Ear pain (particularly on one side, with no other ear problems): Ear pain, also known as otalgia, happens because the nerves of the throat reach the brain through the same pathway as one of the nerves in the ear. Therefore, the brain might think a pain in the throat is coming from the ear. This is called referred pain. For this reason, unexplained ear pain that doesn’t go away should be evaluated by a specialist. It is important to understand that most causes of ear pain are due to simple problems such as middle ear infection, dysfunction of the Eustachian tube, or TMJ pain due to a problem in the joint located in front of the ear.
  • Pain or difficulty with swallowing in the throat: This can occur because a tumor is in the way of swallowing, so it becomes difficult or painful to swallow. Also, there can be ulceration (an area of dead cells) and bleeding as the tumor grows, causing pain.

Other possible symptoms include:

  • Weight loss
  • Feeling like there’s something stuck in the throat
  • Bleeding from the mouth
  • Coughing when drinking liquids
  • Difficult or noisy breathing

These symptoms sound scary, but don’t jump to conclusions. A person could have one or more of these symptoms but NOT have laryngeal cancer. There are several non-cancerous causes of the same symptoms. That’s why the patient needs to see a specialist.

What will happen at the doctor visit

Step 1: History

First, the doctor will listen to the patient talk about his or her health. The doctor will probably ask many questions, too.

The doctor might ask some of these questions:

  • How long has the problem been there?
  • Is it getting worse, better or staying the same?
  • Does it come and go?
  • Have you tried anything to make it better?
  • Is it painful?
  • Do you have numbness or tingling anywhere in your face or mouth?
  • Do you have any lumps or bumps in your neck?
  • Are you losing weight?
  • Do you have any other medical conditions?
  • Have you had any surgeries in the past?
  • What medications do you take? And do you have any allergies?
  • Have you ever been exposed to radiation in the head and neck?
  • What do you (or did you) do for a living?
  • Do you have a family history of cancer?

Step 2: Physical Exam

Next, the doctor will look at and feel the patient’s head and neck. The throat typically requires a specialist to examine it because it is not easy for a general doctor to see and feel. In general, the specialist might do some of the following:

  • Feel the neck extensively and carefully to check for any lumps or bumps
  • Look inside the ears
  • Look inside the front of the nose
  • Check the cranial nerves, do some simple hearing tests and test sense of touch all over the face

Step 3: Reviewing Tests

After getting background information and doing a physical exam, the doctor will look at the results of any tests the patient has already had.

Step 4: Suggestions

Finally, the doctor will make suggestions about next steps. This will probably include more tests and doctor visits.

Diagnosing laryngeal cancer

If the symptoms haven’t been present for very long, or if the history and physical examination make the doctor less worried that the lesion is cancer, the doctor might try some medications and rehabilitation before jumping to a diagnosis of cancer.

However, if the doctor is worried, he or she may choose one or more of the following actions.

Imaging

Imaging refers to radiologic studies, or scans, that make pictures of the structures inside the head and neck. In general, imaging might not be necessary for small tumors that can be easily seen by the doctor. For larger tumors, or tumors in locations difficult to examine, the doctor will probably order some sort of imaging to get more information about the tumor location to see if the tumor has spread to nearby lymph nodes. An important reason to get a scan for sinonasal tumors is to see if there is any evidence of spread into nearby structures. Spread into other structures will influence what treatment the doctor recommends.

Some surgeons also say getting some imaging (pictures of the inside of the head and neck) will lower the chance of surprises in the operating room. Imaging will also give some clues about whether the tumor is really cancer. This will prepare the patient and the surgeon for what to expect during surgery.

There are many different kinds of imaging scans. The doctor may recommend more than one kind of scan to see a better picture of the tumor.

The two main types of imaging used in the U.S. are CT scans and MRI scans.

CT SCAN MRI
 CT Scan  MRI
Advantages A computed tomography (CT) scan is a quick test that shows a great deal of useful information. A CT scan can show the size of the tumor and how far it has spread. It can help a surgeon plan an operation. Magnetic resonance imaging (MRI) is better at showing how the tumor has spread to body parts around it. The patient will not be exposed to radiation during an MRI.
Disadvantages A CT scan uses radiation, which can be dangerous. The pictures might not be clear if the patient moves or has a lot of dental work. Also, a CT doesn’t show damage to nearby body parts as clearly unless the damage is moderate to severe. An MRI takes a lot longer than a CT scan. It requires the patient to lie perfectly still for almost an hour. The patient can’t have an MRI if he or she has metal implants.

For most head and neck cancers, if imaging is required, the doctor will likely start with a CT scan with contrast. Other tests might include an MRI and/or a positron emission tomography (PET) scan.

Biopsy

A biopsy is the main way to find out if a growth is cancer. For a biopsy, the doctor takes out a small piece of the lump or the entire tumor. Another doctor, called a pathologist, then looks at the sample under a microscope to see if it is cancer. Doctors often do biopsies because they can usually be done quickly and safely. The doctor can sometimes do a biopsy during the first visit with very little risk.

Fortunately, biopsies of the skin are more straightforward than for other sites, mainly because they are easier to get to. Typically, skin cancers can be biopsied in the office with a little numbing medicine. It usually takes only a few seconds to do a biopsy. The tissue is then sent to a pathology doctor to see if it is cancer and, if so, what type and how far it has spread.

A biopsy can help the doctor plan the surgery if he or she decides it is needed. A biopsy can also prevent unnecessary surgery.

As good as biopsies sound, there are a few problems. First, biopsies are not 100 percent accurate. A biopsy could show that a growth is NOT cancer when it really is; this is called a false-negative biopsy. A false-positive is also possible when the biopsy seems to show that a growth is cancer but more testing shows it isn’t. Sometimes doctors can’t be completely sure a tumor is cancerous from a biopsy.7 El-Serag HB, Hepworth EJ, Lee P, Sonnenberg A. Gastroesophageal reflux disease is a risk factor for laryngeal and pharyngeal cancer. Am J Gastroenterol. Jul 2001;96(7):2013-8.

Determining the type of laryngeal cancer

After the tumor has been closely looked at, the doctor will need to figure out what type of cancer it is. He or she may be able to tell from biopsy results. The doctor may also want a second opinion from a specialist to be sure. Remember, not all lumps and bumps inside the throat are cancer. Some growths are benign (non-cancerous), and some tumors are on the border between benign and malignant (cancerous).

  • Squamous cell carcinoma: These are by far the most common laryngeal cancers. They arise from cells lining the larynx.

Rare cancers found in the larynx include:

  • Lymphoma: Lymphoma is cancer of the lymphatic system, which includes lymph nodes, lymph channels, lymphatic fluid and lymphoid tissue. The throat is lined with lymphoid cells. Some major sites of lymphoid tissue include the adenoids in the nasopharynx and palatine tonsils and lingual tonsils in the oropharynx. This is why lymphoma might appear as a lump in the throat area.
  • Mucosal melanoma: These cancers come from skin cells that give skin its color. In rare cases, melanoma can be found in the lining of the mouth, nose and/or throat.

Although extremely rare, these cancers can also develop in the larynx:

  • Sarcomas such as chondsarcoma, liposarcoma and synovial sarcoma
  • Malignant fibrous histiocytoma
  • Peripheral Neuroectodermal Tumor (PNET)
  • Cancer spread from another site

The doctor will determine the treatment for the cancer based on the category (type), grade (abnormality) and stage (severity) of the tumor.

Determining the grade of the tumor

Pathologists will typically report on the grade of the tumor. This is a qualitative interpretation by the pathologist of how much the cancerous cells resemble normal tissue from that site. There are a number of different grading systems that might be used. The most common is as follows:

  • GX: Grade cannot be assessed
  • G1: Well differentiated
  • G2: Moderately differentiated
  • G3: Poorly differentiated
  • G4: Undifferentiated

Differentiation refers to how closely the cells taken from a tumor or lesion resemble normal cells from the healthy tissue surrounding the tumor. “Well differentiated” means that the cells look similar to normal cells in that area. “Undifferentiated” means the cells look nothing like normal cells in that area.

While it is important to report the tumor’s grade, few doctors use this information to make decisions regarding treatment or prognosis for this particular cancer type.

Determining the stage of the cancer

The final step before treatment is identifying the stage or the extent of the cancer. This will be determined by studying the physical exam, imaging studies, laboratory work and biopsies.

Like with all cancers of the head and neck, doctors in the U.S. use the AJCC Cancer Staging Manual (7th Ed) to figure out the stage based on three factors.

Factors that go into determining the stage of the cancer
T Characteristics of the main tumor mass
N Status of the lymph nodes in the neck (i.e., evidence of cancer spread)
M Status of cancer spread to parts of the body outside of the head and neck

T stage: the main tumor

Based on a physical examination and review of any imaging, the doctor should be able to assign a T stage that falls within one of the following categories.

38_3_subglottis_Tstage

Subglottis T-stages

38_1_supraglottis_Tstage

Supraglottis T-stages

38_2_glottis_Tstage

Glottis T-stages

 

Tx The doctor is unable to find main tumor.
T0 There is no evidence of a main tumor despite looking everywhere.
Tis Carcinoma in situ (or severe dysplasia); this means there are cancer type cells, but they have not yet invaded deep into tissue. This is more of a pre-cancer lesion.
T1 Supraglottis: The tumor is only at one subsite of the supraglottis, and the vocal cords move normally. Glottis: The tumor is only in the vocal cords with normal mobility. T1a refers to cancer involvement of only one cord. T1b refers to cancer involvement of both cords. Subglottis: The tumor is entirely within the subglottis.
T2 Supraglottis: The tumor invades more than one subsite of the supraglottis, or glottis, or a region outside the supraglottis that is immediately next to where the tumor starts. Also, there is no fixation of the vocal cords. Glottis: The tumor is large enough that it extends to the supraglottis and/or subglottis, and/or there is decreased movement of the vocal cord. Subglottis: The tumor extends up to the vocal cord(s) with normal or decreased mobility.
T3 Supraglottis: The tumor is contained within the voice box, and there is vocal cord fixation and/or it invades any of the following regions: postcricoid area, preepiglottic space, paraglottic space and/or inner aspect of the thyroid cartilage. Glottis:The tumor is contained within the voice box with fixation of the vocal cord, and/or invasion of the paraglottic space and/or invasion of the inside aspect of the thyroid cartilage. Subglottis: The tumor is contained within the voice box and there is vocal cord fixation.
T4a Supraglottis: Moderate advanced local disease. Tumor invades through the thyroid cartilage and/or invades tissues outside of the voice box (such as the trachea, soft tissues of the neck including deep extrinsic muscles of the tongue, strap muscles, thyroid gland or esophagus). Glottis: Moderate advanced local disease. Tumor invades through the thyroid cartilage and/or invades tissues outside of the voice box (such as the trachea, soft tissues of the neck including deep extrinsic muscles of the tongue, strap muscles, thyroid gland or esophagus). Subglottis: Moderate advanced local disease. Tumor invades the thyroid or cricoid cartilage and/or invades tissues outside of the voice box (such as the trachea, soft tissues of the neck including deep extrinsic muscles of the tongue, strap muscles, thyroid gland or esophagus).
T4b Supraglottis: Very advanced local disease. The tumor invades the prevertebral space, encases the carotid artery or invades structures in the upper chest area. Glottis: Very advanced local disease. The tumor invades the prevertebral space, encases the carotid artery or invades structures in the upper chest area. Subglottis: Very advanced local disease. The tumor invades the prevertebral space, encases the carotid artery or invades structures in the upper chest area.

N stage: spread of cancer to the lymph nodes in the neck

Next, the doctor will use all the available information to figure out the N stage. This is based on the assessment as to whether the cancer has spread to lymph nodes in the neck.

06_Nstages

Nx The neck lymph nodes cannot be assessed.
N0 There is no evidence of any spread to the lymph nodes.
N1 The cancer has spread to a single lymph node, on the same side of the main tumor, that is 3 centimeters or less in greatest size.
N2a The cancer has spread to a single lymph node on the same side as the main tumor, and it is more than 3 centimeters but less than or equal to 6 centimeters in greatest size.
N2b There is more than one lymph node that has cancer on the same side as the main tumor, but none of them are more than 6 centimeters.
N2c There are cancerous lymph nodes in the neck on either the opposite side as the main cancer or on both sides of the neck, but none are more than 6 centimeters.
N3 The cancer has spread to one or more neck lymph nodes, and the size is more than 6 centimeters.

M stage: spread of cancer outside the head and neck

Finally, the doctor will identify an M stage. The M stage is based on an examination of the entire body.

M0 No evidence of distant (outside the head and neck) spread.
M1 There is evidence of spread outside of the head and neck (i.e., in the lungs, bone, brain, etc.).

The cancer stage

After TNM staging, the doctor can assign a cancer stage based on the following chart.

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

The clinical stage

Once the tests are completed, and before deciding on a treatment plan, the patient should be given a clinical stage that looks like this:

CLINICAL STAGE
Site Larynx
Subsite Supraglottis
Type Squamous Cell Carcinoma
cT cT3
cN cN2b
cM cM0
cStage cIVa

Deciding on a treatment plan

Like with all cancers in the head and neck, there are three general treatment options:

Let’s look at the types of treatments available.

Surgery

The main treatment for almost all laryngeal cancers is complete surgical removal of the tumor. The surgeon will cut out the tumor plus a little bit of normal tissue around it to be sure to get all the cancer. Another doctor, called a pathologist, will look at the entire tumor under a microscope to identify a more exact stage for the tumor. This report, called the pathologic stage, can help the doctor decide if radiation and/or chemotherapy are needed.

Radiation

Radiation therapy kills cancer cells with high-energy radiation such as X-rays or gamma rays. Radiation may be used as a main treatment for tumors that cannot be easily removed. The surgeon will use radiation alone or radiation with chemotherapy, depending on the characteristics of the tumor. Radiation is also often used after surgery to lower the chances that the tumor will come back.

Chemotherapy

Chemotherapy, or “chemo,” uses drugs to kill cancer cells. It is especially helpful when:

  • Cancer has spread beyond the head and neck.
  • There is a T3 or T4 tumor in which surgery cannot remove all of the tumor.
  • There is a T3 or T4 tumor that has certain bad features found under the microscope, such as intermediate or high grade.
  • There are close edges.
  • There is growth into nerves.
  • There is spread into lymph nodes.
  • There is growth into lymphatics or vessels.

Determining the prognosis

The prognosis is a prediction of how the treatment will turn out. How likely is it that a person with cancer will be cured? Will the cancer come back? How will life change? These are the big questions on most people’s minds when they find out that someone they love has laryngeal cancer.

Prognosis is based on many factors, and a survival rate is an estimate based on large populations of patients who have been given a similar stage of their laryngeal cancer. There are many specific factors that are unique to each patient that may influence treatment success.

The following aspects of the cancer may affect the prognosis.

Stage This is the most important factor that affects the chances of being cured.
Spread to Lymph Nodes Spread of Cancer Cells Outside Lymph Node Capsule Another important factor. If there is cancerous spread to lymph nodes in the neck, there is a lower chance of a cure –especially if the cancer has spread outside of the lymph nodes.
Tumor Margins The ability to completely remove the tumor can be a very important factor that will influence the likelihood of being cured.
Spread into Local Structures Cancerous spread into large nerves, vessels, lymphatics or elsewhere might make the prognosis worse.

What to expect after treatment is completed

When the person in your life who has cancer has completed treatment, he or she will need to follow up closely with the doctor. Follow-up doctor visits and testing are to make sure the cancer doesn’t come back or to catch it quickly if it does. In general, a person should have regularly scheduled doctor’s visits every one to three months for the first year, every two to six months in the second year and every four to eight months in the third to fifth year. In addition, the doctor will order scans to help in the monitoring process. After making it past the first five years, the person can then see the doctor once a year.


References

1 Muscat JE, Wynder EL. Tobacco, alcohol, asbestos, and occupational risk factors for laryngeal cancer. Cancer. May 1 1992;69(9):2244-2251.

2 Lewin F, Norell SE, Johansson H, et al. Smoking tobacco, oral snuff, and alcohol in the etiology of squamous cell carcinoma of the head and neck: a population-based case-referent study in Sweden. Cancer. Apr 1 1998;82(7):1367-1375.

3 Lynch HT, Mulcahy GM, Harris RE, Guirgis HA, Lynch JF. Genetic and pathologic findings in a kindred with hereditary sarcoma, breast cancer, brain tumors, leukemia, lung, laryngeal, and adrenal cortical carcinoma. Cancer. May 1978;41(5):2055-2064.

4 Katsenos S, Becker HD. Recurrent respiratory papillomatosis: a rare chronic disease, difficult to treat, with potential to lung cancer transformation: apropos of two cases and a brief literature review. Case Rep Oncol. 2011 Mar 23;4(1):162-71.

5 Burch JD, Howe GR, Miller AB, Semenciw R. Tobacco, alcohol, asbestos, and nickel in the etiology of cancer of the larynx: a case-control study. Journal of the National Cancer Institute. Dec 1981;67(6):1219-1224.

6 NCCN Guidelines version 2.2012. Esophageal and esophagogastric junction cancers. Principles of Endoscopic Staging and Therapy. NCCN 2013.

7 El-Serag HB, Hepworth EJ, Lee P, Sonnenberg A. Gastroesophageal reflux disease is a risk factor for laryngeal and pharyngeal cancer. Am J Gastroenterol. Jul 2001;96(7):2013-8.

8 Vaezi MF, Qadeer MA, Lopez R, Colabianchi N. Laryngeal cancer and gastroesophageal reflux disease: a case-control study. Am J Med. Sep 2006;119(9):768-76.

9 Hoare TJ, Thomson HG, Proops DW. Detection of laryngeal cancer--the case for early specialist assessment. Journal of the Royal Society of Medicine. Jul 1993;86(7):390-392.

10 Spiro RH, Thaler HT, Hicks WF, Kher UA, Huvos AH, Strong EW. The importance of clinical staging of minor salivary gland carcinoma. Am J Surg. 1991 Oct;162(4):330-6.

11 Krause CJ, Carey TE, Ott RW, Hurbis C, McClatchey KD, Regezi JA. Human squamous cell carcinoma. Establishment and characterization of new permanent cell lines. Arch Otolaryngol. Nov 1981;107(11):703-710.

12 Mantravadi RV, Liebner EJ, Haas RE, Skolnik EM, Applebaum EL. Cancer of the glottis: prognostic factors in radiation therapy. Radiology. Oct 1983;149(1):311-314.

13 Bocca E. Supraglottic cancer. Laryngoscope. Aug 1975;85(8):1318-1326.

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