Head and Neck Cancer

1. What are the Causes for Head and Neck Cancer?
2. What are the Symptoms of Head and Neck Cancer?
3. Classification
     3.1 Oral cavity
     3.2 Nasopharynx
     3.3 Oropharynx
     3.4 Hypopharynx
     3.5 Larynx
     3.6 Trachea
4. Diagnosis
5. Methods of Treatment
     5.1 General considerations
     5.2 Surgery
     5.3 Radiation therapy
     5.4 Chemotherapy
     5.5 Photodynamic therapy
     5.6 Targeted therapy
6. Drugs rating
7. Prognosis
     7.1 Residual deficits
     7.2 Problem of second primaries
     7.3 Digestive system
     7.4 Respiratory system
     7.5 Others
8. What rehabilitation or support options are available for patients with head and neck cancers?
9. Follow-up
10. Discussion and questions

The term head and neck cancer refers to a group of biologically similar cancers originating from the upper aerodigestive tract, including the lip, oral cavity (mouth), nasal cavity, paranasal sinuses, pharynx, and larynx. Most head and neck cancers are squamous cell carcinomas (SCCHN), originating from the mucosal lining (epithelium) of these regions.

Head and neck cancers often spread to the lymph nodes of the neck, and this is often the first (and sometimes only) manifestation of the disease at the time of diagnosis. Head and neck cancer is strongly associated with certain environmental and lifestyle risk factors, including tobacco smoking, alcohol consumption, UV light and occupational exposures, and certain strains of viruses, such as the sexually transmitted human papillomavirus. These cancers are frequently aggressive in their biologic behavior; patients with these types of cancer often develop a second primary tumor. Head and neck cancer is highly curable if detected early, usually with some form of surgery although chemotherapy and radiation therapy may also play an important role.

The 2009 estimated number of head and neck cancer in the US is of 35,720 new cases.

What are the Causes for Head and Neck Cancer?

Tobacco (including smokeless tobacco, sometimes called “chewing tobacco” or “snuff”) and alcohol use are the most important risk factors for head and neck cancers, particularly those of the oral cavity, oropharynx, hypopharynx, and larynx. Eighty-five percent of head and neck cancers are linked to tobacco use. People who use both tobacco and alcohol are at greater risk for developing these cancers than people who use either tobacco or alcohol alone.

Other risk factors for cancers of the head and neck include the following:

• Oral cavity. Sun exposure (lip); possibly human papillomavirus (HPV) infection.
• Salivary glands. Radiation to the head and neck. This exposure can come from diagnostic x-rays or from radiation therapy for noncancerous conditions or cancer.
• Paranasal sinuses and nasal cavity. Certain industrial exposures, such as wood or nickel dust inhalation. Tobacco and alcohol use may play less of a role in this type of cancer.
• Nasopharynx. Asian, particularly Chinese, ancestry; Epstein-Barr virus infection; occupational exposure to wood dust; and consumption of certain preservatives or salted foods.
• Oropharynx. Poor oral hygiene; HPV infection and the use of mouthwash that has a high alcohol content are possible, but not proven, risk factors.
• Hypopharynx. Plummer-Vinson (also called Paterson-Kelly) syndrome, a rare disorder that results from iron and other nutritional deficiencies. This syndrome is characterized by severe anemia and leads to difficulty swallowing due to webs of tissue that grow across the upper part of the esophagus.
• Larynx. Exposure to airborne particles of asbestos, especially in the workplace.

Immigrants from Southeast Asia who use paan (betel quid) in the mouth should be aware that this habit has been strongly associated with an increased risk for oral cancer. Also, consumption of mate, a tea-like beverage habitually consumed by South Americans, has been associated with an increased risk of cancers of the mouth, throat, esophagus, and larynx.

People who are at risk for head and neck cancers should talk with their doctor about ways they can reduce their risk. They should also discuss how often to have checkups.

What are the Symptoms of Head and Neck Cancer?

Symptoms of several head and neck cancer sites include a lump or sore that does not heal, a sore throat that does not go away, difficulty swallowing, and a change or hoarseness in the voice. Other symptoms may include the following:

• Oral cavity. A white or red patch on the gums, tongue, or lining of the mouth; a swelling of the jaw that causes dentures to fit poorly or become uncomfortable; and unusual bleeding or pain in the mouth.
• Nasal cavity and sinuses. Sinuses that are blocked and do not clear, chronic sinus infections that do not respond to treatment with antibiotics, bleeding through the nose, frequent headaches, swelling or other trouble with the eyes, pain in the upper teeth, or problems with dentures.
• Salivary glands. Swelling under the chin or around the jawbone; numbness or paralysis of the muscles in the face; or pain that does not go away in the face, chin, or neck.
• Oropharynx and hypopharynx. Ear pain.
• Nasopharynx. Trouble breathing or speaking, frequent headaches, pain or ringing in the ears, or trouble hearing.
• Larynx. Pain when swallowing, or ear pain.
• Metastatic squamous neck cancer. Pain in the neck or throat that does not go away.

These symptoms may be caused by cancer or by other, less serious conditions. It is important to check with a doctor or dentist about any of these symptoms.

Classification

Head and neck squamous cell carcinomas (HNSCC’s) make up the vast majority of head and neck cancers, and arise from mucosal surfaces throughout this anatomic region. These include tumors of the nasal cavities, paranasal sinuses, oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx.

Oral cavity

Squamous cell cancers are common in the oral cavity, including the inner lip, tongue, floor of mouth, gingivae, and hard palate. Cancers of the oral cavity are strongly associated with tobacco use, especially use of chewing tobacco or “dip”, as well as heavy alcohol use. Cancers of this region, particularly the tongue, are more frequently treated with surgery than are other head and neck cancers.

Surgeries for oral cancers include

• Maxillectomy (can be done with or without Orbital exenteration)
• Mandibulectomy (removal of the mandible or lower jaw or part of it)
• Glossectomy (tongue removal, can be total, hemi or partial)
• Radical neck dissection
• Moh’s procedure
• Combinational e.g. glossectomy and laryngectomy done together.

The defect is covered/improved by using another part of the body and/or skin grafts and/or wearing a prosthesis.

Nasopharynx

Nasopharyngeal cancer arises in the nasopharynx, the region in which the nasal cavities and the Eustachian tubes connect with the upper part of the throat. While some nasopharyngeal cancers are biologically similar to the common HNSCC, “poorly differentiated” nasopharyngeal carcinoma is distinct in its epidemiology, biology, clinical behavior, and treatment, and is treated as a separate disease by many experts.

Oropharynx

Oropharyngeal squamous cell carcinomas (OSCC) begins in the oropharynx, the middle part of the throat that includes the soft palate, the base of the tongue, and the tonsils. Squamous cell cancers of the tonsils are more strongly associated with human papillomavirus infection than are cancers of other regions of the head and neck.

Hypopharynx

The hypopharynx includes the pyriform sinuses, the posterior pharyngeal wall, and the postcricoid area. Tumors of the hypopharynx frequently have an advanced stage at diagnosis, and have the most adverse prognoses of pharyngeal tumors. They tend to metastasize early due to the extensive lymphatic network around the larynx.

Larynx

Laryngeal cancer begins in the larynx or “voice box.” Cancer may occur on the vocal folds themselves (“glottic” cancer), or on tissues above and below the true cords (“supraglottic” and “subglottic” cancers respectively). Laryngeal cancer is strongly associated with tobacco smoking.

Surgeries can include partial laryngectomy (removal of part of the larynx) and total laryngectomy (removal of the whole larynx). If the whole larynx has been removed the person is left with a permanent tracheostomy opening and learns to speak again in a new way with the help of intensive teaching and speech therapy and/or an electronic device.

Also anyone who has had a glossectomy (tongue removal) will be taught to speak again in a new way and have intensive speech therapy.

Trachea

Cancer of the trachea is a rare malignancy which can be biologically similar in many ways to head and neck cancer, and is sometimes classified as such.

Most tumors of the salivary glands differ from the common carcinomas of the head and neck in etiology, histopathology, clinical presentation, and therapy, Other uncommon tumors arising in the head and neck include teratomas, adenocarcinomas, adenoid cystic carcinomas, and mucoepidermoid carcinomas. Rarer still are melanomas and lymphomas of the upper aerodigestive tract.

Diagnosis

To find the cause of symptoms, a doctor evaluates a person’s medical history, performs a physical examination, and orders diagnostic tests. The exams and tests conducted may vary depending on the symptoms. Examination of a sample of tissue under the microscope is always necessary to confirm a diagnosis of cancer.

Some exams and tests that may be useful are described below:

• Physical examination may include visual inspection of the oral and nasal cavities, neck, throat, and tongue using a small mirror and/or lights. The doctor may also feel for lumps on the neck, lips, gums, and cheeks.
• Endoscopy is the use of a thin, lighted tube called an endoscope to examine areas inside the body. The type of endoscope the doctor uses depends on the area being examined. For example, a laryngoscope is inserted through the mouth to view the larynx; an esophagoscope is inserted through the mouth to examine the esophagus; and a nasopharyngoscope is inserted through the nose so the doctor can see the nasal cavity and nasopharynx.
• Laboratory tests examine samples of blood, urine, or other substances from the body.
• X-rays create images of areas inside the head and neck on film.
• CT (or CAT) scan is a series of detailed pictures of areas inside the head and neck created by a computer linked to an x-ray machine.
• Magnetic resonance imaging (or MRI) uses a powerful magnet linked to a computer to create detailed pictures of areas inside the head and neck.
• PET scan uses sugar that is modified in a specific way so it is absorbed by cancer calls and appears as dark areas on the scan.
• Biopsy is the removal of tissue. A pathologist studies the tissue under a microscope to make a diagnosis. A biopsy is the only sure way to tell whether a person has cancer.

If the diagnosis is cancer, the doctor will want to learn the stage (or extent) of disease. Staging is a careful attempt to find out whether the cancer has spread and, if so, to which parts of the body. Staging may involve an examination under anesthesia (in the operating room), x-rays and other imaging procedures, and laboratory tests. Knowing the stage of the disease helps the doctor plan treatment.

Methods of Treatment

General considerations

Improvements in diagnosis and local management, as well as targeted therapy, have led to improvements in quality of life and survival for head and neck cancer patients since 1992.

After a histologic diagnosis has been established and tumor extent determined, the selection of appropriate treatment for a specific cancer depends on a complex array of variables, including tumor site, relative morbidity of various treatment options, patient performance and nutritional status, concomitant health problems, social and logistic factors, previous primary tumors, and patient preference. Treatment planning generally requires a multidisciplinary approach involving specialist surgeons and medical and radiation oncologists.

Several generalizations are useful in therapeutic decision making, but variations on these themes are numerous. Surgical resection and radiation therapy are the mainstays of treatment for most head and neck cancers and remain the standard of care in most cases. For small primary cancers without regional metastases (stage I or II), wide surgical excision alone or curative radiation therapy alone is used. More extensive primary tumors, or those with regional metastases (stage III or IV), planned combinations of pre- or postoperative radiation and complete surgical excision are generally used. More recently, as historical survival and control rates are recognized as less than satisfactory, there has been an emphasis on the use of various induction or concomitant chemotherapy regimens.

Patients with head and neck cancer can be categorized into three clinical groups: those with localized disease, those with locally or regionally advanced disease, and those with recurrent and/or metastatic disease. Comorbidities (medical problems in addition to the diagnosed cancer) associated with tobacco and alcohol abuse can affect treatment outcome and the tolerability of aggressive treatment in a given patient.

Many different treatments and therapies are used in the treatment of throat cancer. The type of treatment and therapies used are largely determined by the location of the cancer in the throat area and also the extent to which the cancer has spread at time of diagnosis. Patients’ also have the right to decide whether or not they wish to consent to a particular treatment. For example, some may decide to not undergo radiation therapy which has serious side effects if it means they will be extending their lives by only a few months or so. Others may feel that the extra time is worth it and wish to pursue the treatments.

Surgery

Surgery as a treatment is sometimes used in cases of throat cancer. In such cases an attempt is made to remove the cancerous cells. This can be particularly tricky if the cancer is near the larynx and can result in the patient being unable to speak. Surgery is more commonly used to resection (remove) some of the lymph nodes to prevent further spread of the disease. A novel approach uses harvested hematopoietic stem cells (blood stem cells) and other harvested cells (if necessary, a silicon alloy can also be used or can be used in place of the cells) from the lining of the patient’s stomach to form a new section of a trachea or esophagus.

CO2 laser surgery is also another form of treatment. Transoral laser microsurgery allows surgeons to remove tumors from the voice box with no external incisions. It also allows access to tumors that are not reachable with robotic surgery. A microscope helps the surgeon clearly view the margins of the tumor, minimizing the amount of normal tissue removed or damaged during surgery. This technique helps give the patient as much speech and swallowing function as possible after surgery.

Radiation therapy

Radiation therapy is the most common form of treatment. There are different forms of radiation therapy. One of newer treatments is Intensity-modulated radiotherapy or IMRT which is able to focus more precisely so that fewer healthy cells are destroyed than was the case with some of the older radiation therapies. IMRT reduces incidental damage to the many important structures of the throat and mouth that may not be involved. However, if the cancer has metastisized or is widespread, the older form of treatment may be the most effective at slowing the progression of the disease. Radiation will generally cause the patient to feel sicker and weaker for several weeks following the treatment, but is a very effective treatment in stopping the disease.

Chemotherapy

Chemotherapy in throat cancer is not generally used to cure the cancer as such. Instead, it is used to provide an inhospitable environment for metastases so that they will not establish in other parts of the body. Typical chemotherapy agents are a combination of Taxol and Carboplatin. Erbitux is also used in the treatment of throat cancer. While not specifically a chemotherapy, Amifostine is often administered intravenously by a chemotherapy clinic prior to a patient’s radiotherapy sessions. Amifostine protects the patient’s gums and salivary glands from the effects of radiation.

Photodynamic therapy

Photodynamic therapy may have promise in treating mucosal dysplasia and small head and neck tumors. Amphinex is giving good results in early clinical trials for treatment of advanced head and neck cancer.

Targeted therapy

Targeted therapy, according to the National Cancer Institute, is “a type of treatment that uses drugs or other substances, such as monoclonal antibodies, to identify and attack specific cancer cells without harming normal cells.” Some targeted therapy used in squamous cell cancers of the head and neck include cetuximab, bevacizumab, erlotinib, and reovirus.

The best quality data are available for cetuximab since the 2006 publication of a randomized clinical trial comparing radiation treatment plus cetuximab versus radiation treatment alone. This study found that concurrent cetuximab and radiotherapy improves survival and locoregional disease control compared to radiotherapy alone, without a substantial increase in side effects, as would be expected with the concurrent chemoradiotherapy, which is the current gold standard treatment for advanced head and neck cancer. Whilst this study is of pivotal significance, interpretation is difficult since cetuximab-radiotherapy was not directly compared to chemoradiotherapy. The results of ongoing studies to clarify the role of cetuximab in this disease are awaited with interest.

Another study evaluated the impact of adding cetuximab to conventional chemotherapy (cisplatin) versus cisplatin alone. This study found no improvement in survival or disease-free survival with the addition of cetuximab to the conventional chemotherapy.

However, another study which completed in March 2007 found that there was an improvement in survival.

The EXTREME (Erbitux in First-Line Treatment of Recurrent or Metastatic Head & Neck Cancer) study is a European multicenter phase III trial to determine whether adding cetuximab improves the impact of platinum-based chemotherapy.

Between December 2004 and March 2007, researchers enrolled 442 patients in 17 countries who had stage III or IV recurrent and/or metastatic SCCHN, and who were not candidates for further surgery or radiation. About half of the patients had cancer in their pharynx (throat), and a quarter in their larynx (voice box), but none in the nasopharynx (upper part of the throat). The patients averaged 57 years of age. Only about 10 percent were women.

Patients were randomly assigned to receive either chemotherapy (222 patients) or the same chemotherapy with cetuximab (220 patients). Chemotherapy consisted of 5-fluorouracil plus either carboplatin or cisplatin.

The trial was led by Jan Vermorken, M.D., Ph.D., of the University of Antwerp in Belgium. Vermmorken as well as other researchers involved in the trial have various relationships with Merck KGaA, Amgen, Oxygene, and sanofi-aventis. Merck KGaA provided funding for the study. (See the protocol summary.)

Results Patients treated with cetuximab reduced their risk of dying by 20 percent, surviving a median of 10.1 months compared to 7.4 months for those receiving chemotherapy alone.

Head and neck cancer clinical trials employing bevacizumab, an inhibitor of the angiogenesis receptor VEGF, are recruiting patients as of March, 2007. No published clinical trial information is available as of that date.

Erlotinib is an oral EGFR inhibitor, and was found in one Phase II clinical trial to retard disease progression. Scientific evidence for the effectiveness of erlotinib is otherwise lacking to this point. A clinical trial evaluating the use of erlotinib in metastatic head and neck cancer is recruiting patients as of March, 2007.

Reovirus is an oncolytic virus that targets RAS activated cancer cells. Trial update on November 2008 showed stable disease or better in the first eight of nine patients with refractory head and neck cancer. Phase II trials are ongoing in England and the USA with phase III trials planned.

Drugs rating:

Prognosis

Although early-stage head and neck cancers (especially laryngeal and oral cavity) have high cure rates, up to 50% of head and neck cancer patients present with advanced disease. Cure rates decrease in locally advanced cases, whose probability of cure is inversely related to tumor size and even more so to the extent of regional node involvement. Consensus panels in America (AJCC) and Europe (UICC) have established staging systems for head and neck squamous cancers. These staging systems attempt to standardize clinical trial criteria for research studies, and attempt to define prognostic categories of disease. Squamous cell cancers of the head and neck are staged according to the TNM classification system, where T is the size and configuration of the tumor, N is the presence or absence of lymph node metastases, and M is the presence or absence of distant metastases. The T, N, and M characteristics are combined to produce a “stage” of the cancer, from I to IVB.

Residual deficits

Even after successful definitive therapy, head and neck cancer patients face tremendous impacts on quality of life. Despite marked advances in reconstructive surgery and rehabilitation, intensity-modulated radiotherapy (IMRT) and conservation approaches to certain malignancies, some patients continue to have significant functional deficits.

Problem of second primaries

Survival advantages provided by new treatment modalities have been undermined by the significant percentage of patients cured of head and neck squamous cell carcinoma (HNSCC) who subsequently develop second primary tumors. The incidence of second primary tumors ranges in studies from 9.1% to 23% at 20 years. Second primary tumors are the major threat to long-term survival after successful therapy of early-stage HNSCC. Their high incidence results from the same carcinogenic exposure responsible for the initial primary process, called field cancerization.

Throat cancer has numerous negative effects on the body systems.

Digestive system

As it can impair a person’s ability to swallow and eat, throat cancer affects the digestive system. The difficulty in swallowing can lead to a person to choke on their food in the early stages of digestion and interfere with the food’s smooth travels down into the esophagus and beyond.

The treatments for throat cancer can also be harmful to the digestive system as well as other body systems. Radiation therapy can lead to nausea and vomiting, which can deprive a body of vital fluids (although these may be obtained through intravenous fluids if necessary). Frequent vomiting can lead to an electrolyte imbalance which has serious consequences for the proper functioning of the heart. Frequent vomiting can also upset the balance of stomach acids which has a negative impact on the digestive system, especially the lining of the stomach and esophagus.

Respiratory system

In the cases of some throat cancers, the air passages in the mouth and behind the nose may become blocked from lumps or the swelling from the open sores. If the throat cancer is near the bottom of the throat it has a high likelihood of spreading to the lungs and interfering with the person’s ability to breathe; this is even more likely if the patient is a smoker, because they are highly susceptible to lung cancer.

Others

Like any cancer, metastasization affects many areas of the body, as the cancer spreads from cell to cell and organ to organ. For example, if it spreads to the bone marrow, it will prevent the body from producing enough red blood cells and affects the proper functioning of the white blood cells and the body’s immune system; spreading to the circulatory system will prevent oxygen from being transported to all the cells of the body; and throat cancer can throw the nervous system into chaos, making it unable to properly regulate and control the body.

What rehabilitation or support options are available for patients with head and neck cancers?

Rehabilitation is a very important part of treatment for patients with head and neck cancer. The goals of rehabilitation depend on the extent of the disease and the treatment a patient has received. The health care team makes every effort to help the patient return to normal activities as soon as possible.

Depending on the location of the cancer and the type of treatment, rehabilitation may include physical therapy, dietary counseling, speech therapy, and/or learning how to care for a stoma after a laryngectomy. A stoma is an opening into the windpipe through which a patient breathes after a laryngectomy.

Sometimes, especially with cancer of the oral cavity, a patient may need reconstructive and plastic surgery to rebuild the bones or tissues of the mouth. If this is not possible, a prosthodontist may be able to make a prosthesis (an artificial dental and/or facial part) to restore satisfactory swallowing and speech. Patients will receive special training to use the device.

Patients who have trouble speaking after treatment, or who have lost their ability to speak, may need speech therapy. Often, a speech-language pathologist will visit the patient in the hospital to plan therapy and teach speech exercises or alternative methods of speaking. Speech therapy usually continues after the patient returns home.

Eating may be difficult after treatment for head and neck cancer. Some patients receive nutrients directly into a vein (IV) after surgery, or need a feeding tube until they can eat on their own. A feeding tube is a flexible plastic tube that is passed into the stomach through the nose or an incision (cut) in the abdomen. A nurse or speech-language pathologist can help patients learn how to swallow again after surgery. The NCI booklet Eating Hints for Cancer Patients: Before, During, and After Treatment contains many useful suggestions and recipes.

Follow-up

Regular follow-up care is very important after treatment for head and neck cancer to make sure the cancer has not returned, or that a second primary (new) cancer has not developed. Depending on the type of cancer, medical checkups could include exams of the stoma, mouth, neck, and throat. Regular dental exams may also be necessary. From time to time, the doctor may perform a complete physical exam, blood tests, x-rays, and CT, PET, or MRI scans. The doctor may continue to monitor thyroid and pituitary gland function, especially if the head or neck was treated with radiation. Also, the doctor is likely to counsel patients to stop smoking. Research has shown that continued smoking may reduce the effectiveness of treatment and increase the chance of a second primary cancer. The NCI fact sheet Follow-up Care: Questions and Answers has more information about this topic.