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| | ==[[Head and neck cancer overview|Overview]]== |
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| ==Overview== | | ==[[Head and neck cancer classification|Classification]]== |
| 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 carcinoma]]s, originating from the [[mucosa]]l lining ([[epithelium]]) of these regions.<ref>[http://www.cancer.gov/templates/doc.aspx?viewid=7BDB0B90-2F6E-48A0-BCEA-00B2920A8933 NCI factsheet on head and neck cancer]</ref> Head and neck cancers often spread to the [[lymph node]]s 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, and certain strains of the sexually transmitted [[human papillomavirus]]. Head and neck cancer is highly curable if detected early, most often through a combination of [[chemotherapy]] and [[radiation therapy]], although [[surgery]] may also play an important role.
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| ==Epidemiology== | | ==[[Head and neck cancer historical perspective|Historical Perspective]]== |
| The number of new cases of head and neck cancers in the United States was 40,490 in 2006, accounting for about 3% of adult malignancies. 11,170 patients died of their disease in 2006.<ref>{{cite journal |author=Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun M |title=Cancer statistics, 2006 |journal=CA Cancer J Clin |volume=56 |issue=2 |pages=106-30 |year= |pmid=16514137}}</ref> The worldwide incidence exceeds half a million cases annually. In North America and Europe, the tumors usually arise from the oral cavity, oropharynx, or larynx, whereas nasopharyngeal cancer is more common in the Mediterranean countries and in the Far East. In Southeast China and Taiwan, head and neck cancer, specifically Nasopharyngeal Cancer is the most common cause of death in young men.<ref>{{cite journal |author=Titcomb C |title=High incidence of nasopharyngeal carcinoma in Asia |journal=J Insur Med |volume=33 |issue=3 |pages=235-8 |year=2001 |pmid=11558403}}</ref>
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| African Americans are disproportionately affected by head and neck cancer, with younger ages of incidence, increased mortality, and more advanced disease at presentation.<ref> {{cite journal |author=Gourin C, Podolsky R |title=Racial disparities in patients with head and neck squamous cell carcinoma |journal=Laryngoscope |volume=116 |issue=7 |pages=1093-106 |year=2006 |pmid=16826042}}</ref>
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| * In the U.S. there were 28,900 people diagnosed with cancers of the throat and oral cavity in 2002.<ref name="ACS">''Cancer Facts and Figures'', http://www.cancer.org/downloads/STT/CancerFacts&Figures2002TM.pdf,, American Cancer Society 2002.</ref>
| | ==[[Head and neck cancer pathophysiology|Pathophysiology]]== |
| * Seventy-four hundred Americans are projected to die of these cancers.<ref name="ACS">1</ref>
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| * More than 70% of throat cancers are at an advanced stage when discovered.<ref name="NCH">''Throat Cancer'' patient information web page, http://cancer.nchmd.org/treatment.aspx?id=741, NCH Healthcare Systems, 1999</ref>
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| * Men are 89% more likely than women to be diagnosed with, and are almost twice as likely to die of, these cancers.<ref name="ACS">1</ref>
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| * African-American men are at a 50% higher risk of throat cancer than Caucasian males.<font color=red><sup></sup></font>
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| * Smoking and tobacco use are directly related to Oro-pharangeal (throat) cancer deaths.<ref name="HHS">''Reducing the Health Consequences of Smoking: 25 Years of Progress. A Report of the Surgeon General'', U. S. Department of Health and Human Services, Public Health Service,Centers for Disease Control and Prevention, 1989.sad</ref>
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| ==Pathophysiology== | | ==[[Head and neck cancer epidemiology and demographics|Epidemiology & Demographics]]== |
| [[ethanol|Alcohol]]<ref>{{cite journal |author=Spitz M |title=Epidemiology and risk factors for head and neck cancer |journal=Semin Oncol |volume=21 |issue=3 |pages=281-8 |year=1994 |pmid=8209260}}</ref>
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| and [[tobacco]] use are the most common risk factors for head and neck cancer in the United States. Alcohol and tobacco are likely synergistic in causing cancer of the head and neck.<ref>{{cite journal |author=Murata M, Takayama K, Choi B, Pak A |title=A nested case-control study on alcohol drinking, tobacco smoking, and cancer |journal=Cancer Detect Prev |volume=20 |issue=6 |pages=557-65 |year=1996 |pmid=8939341}}</ref>
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| Smokeless tobacco is an etiologic agent for oral and [[pharyngeal]] cancers.<ref>{{cite journal |author=Winn D |title=Smokeless tobacco and aerodigestive tract cancers: recent research directions |journal=Adv Exp Med Biol |volume=320 |issue= |pages=39-46 |year= |pmid=1442283}}</ref>
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| [[Cigar]] smoking is an important risk factor for oral cancers as well.<ref>{{cite journal |author=Iribarren C, Tekawa I, Sidney S, Friedman G |title=Effect of cigar smoking on the risk of cardiovascular disease, chronic obstructive pulmonary disease, and cancer in men |journal=N Engl J Med |volume=340 |issue=23 |pages=1773-80 |year=1999 |pmid=10362820}}</ref>
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| Other potential environmental [[carcinogens]] include [[cannabis (drug)|marijuana]] and occupational exposures such as nickel refining, exposure to textile fibers, and woodworking. [[Cigarette]] smokers have a lifetime increased risk for head and neck cancers that is 5- to 25-fold increased over the general population.<ref>{{cite journal |author=Andre K, Schraub S, Mercier M, Bontemps P |title=Role of alcohol and tobacco in the aetiology of head and neck cancer: a case-control study in the Doubs region of France |journal=Eur J Cancer B Oral Oncol |volume=31B |issue=5 |pages=301-9 |year=1995 |pmid=8704646}}</ref>
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| The ex-smoker's risk for squamous cell cancer of the head and neck begins to approach the risk in the general population twenty years after smoking cessation. The high prevalence of tobacco and alcohol use worldwide and the high association of these cancers with these substances makes them ideal targets for enhanced cancer prevention.
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| Dietary factors may contribute. Excessive consumption of processed meats and red meat were associated with increased rates of cancer of the head and neck in one study, while consumption of raw and cooked vegetables seemed to be protective.<ref>{{cite journal |author=Levi F, Pasche C, La Vecchia C, Lucchini F, Franceschi S, Monnier P |title=Food groups and risk of oral and pharyngeal cancer |journal=Int J Cancer |volume=77 |issue=5 |pages=705-9 |year=1998 |pmid=9688303}}</ref>
| | ==[[Head and neck cancer risk factors|Risk Factors]]== |
| [[Vitamin E]] was not found to prevent the development of [[leukoplakia]], the white plaques that are the precursor for carcinomas of the mucosal surfaces, in adult smokers.<ref>{{cite journal |author=Liede K, Hietanen J, Saxen L, Haukka J, Timonen T, Häyrinen-Immonen R, Heinonen O |title=Long-term supplementation with alpha-tocopherol and beta-carotene and prevalence of oral mucosal lesions in smokers |journal=Oral Dis |volume=4 |issue=2 |pages=78-83 |year=1998 |pmid=9680894}}</ref> | |
| Another study examined a combination of [[Vitamin E]] and [[beta carotene]] in smokers with early-stage cancer of the oropharynx, and found a worse prognosis in the vitamin users.<ref>{{cite journal |author=Bairati I, Meyer F, Gélinas M, Fortin A, Nabid A, Brochet F, Mercier J, Têtu B, Harel F, Mâsse B, Vigneault E, Vass S, del Vecchio P, Roy J |title=A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients |journal=J Natl Cancer Inst |volume=97 |issue=7 |pages=481-8 |year=2005 |pmid=15812073}}</ref>
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| Betel-nut chewing is associated with an increased risk of squamous cell cancer of the head and neck.<ref>{{cite journal |author=Jeng J, Chang M, Hahn L |title=Role of areca nut in betel quid-associated chemical carcinogenesis: current awareness and future perspectives |journal=Oral Oncol |volume=37 |issue=6 |pages=477-92 |year=2001 |pmid=11435174}}</ref>
| | ==[[Head and neck cancer screening|Screening]]== |
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| Some head and neck cancers may have a viral etiology.<ref name=AMN>{{cite web | author = Everett E. Vokes | title =Head and Neck Cancer | work =Head and Neck Cancer | url=http://www.health.am/cr/head-and-neck-cancer/ | year = 2006 | month= June 28 | publisher=Armenian Health Network, Health.am | accessdate=2007-09-25}}</ref> The [[DNA]] of [[human papillomavirus]] has been detected in the tissue of oral and tonsil cancers, and may predispose to oral cancer in the absence of [[tobacco]] and [[alcohol]] use. [[Epstein-Barr virus]] (EBV) infection is associated with [[nasopharyngeal carcinoma|nasopharyngeal cancer]].<ref name="AMN" />
| | ==[[Head and neck cancer causes|Causes]]== |
| Nasopharyngeal cancer occurs endemically in some countries of the Mediterranean and Asiat, where EBV [[antibody]] titers can be measured to screen high-risk populations.<ref name="AMN" />
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| Nasopharyngeal cancer has also been associated with consumption of salted fish, which may contain high levels of [[nitrites]].
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| There are a wide variety of factors which can put someone at a heightened risk for throat cancer. Such factors include [[tobacco smoking|smoking]] or [[chewing tobacco|chewing]] [[tobacco]] or other things, such as [[betel]], gutkha, [[cannabis (drug)|marijuana]] or paan, heavy [[alcohol]] consumption, poor diet resulting in [[vitamin]] deficiencies (worse if this is caused by heavy alcohol intake), weakened [[immune system]], [[asbestos]] exposure, prolonged exposure to wood dust or paint fumes, exposure to petroleum industry chemicals, and being over the age of 55 years. Another risk factor includes the appearance of white patches or spots in the mouth, known as [[leukoplakia]]; in about ⅓ of the cases this develops into cancer.
| | ==[[Head and neck cancer differential diagnosis|Differentiating Head and neck cancer from other Diseases]]== |
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| The presence of [[Gastroesophageal reflux disease|acid reflux disease]] (GERD - gastroesphogeal reflux disease) or larynx reflux disease can also be a major factor. In the case of acid reflux disease, stomach acids flow up into the [[esophagus]] and damage its lining, making it more susceptible to throat cancer.
| | ==[[Head and neck cancer natural history|Natural History, Complications & Prognosis]]== |
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| Ethnicitymay also play a part, with African American men in the [U.S.]being found to be at a 50% higher risk of throat cancer than Caucasian men.
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| ==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 cavity|nasal cavities]], [[paranasal sinuses]], [[oral cavity]], [[nasopharynx]], [[oropharynx]], [[hypopharynx]], and [[larynx]].
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| ===Nasal cavity===
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| ===Paranasal sinuses===
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| ===Oral cavity===
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| {{Main|Oral cancer}}
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| Squamous cell cancers are common in the oral cavity, including the inner lip, [[tongue]], floor of mouth, [[gingiva]]e, 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.
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| Surgeries for oral cancers include
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| * Maxillectomy (can be done with or without Orbital exenteration
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| * Mandibulectomy (removal of the mandible or lower jaw or part of it)
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| * Glossectomy (tongue removal, can be total, hemi or partial)
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| * Radical neck dissection
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| * Moh's procedure
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| * Combinational e.g. glossectomy and laryngectomy done together.
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| The defect is covered/improved by using another part of the body and/or skin grafts and/or wearing a [[prosthesis]].
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| ===Nasopharynx===
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| [[Nasopharyngeal carcinoma|Nasopharyngeal cancer]] arises in the [[nasopharynx]], the region in which the [[nasal cavity|nasal cavities]] and the [[Eustachian tube]]s 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.
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| Surgeries for nasal cancer (cancer of the nose)
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| * Surgery to removal the entire nose or part of the nose. Removal of all of the nose is called a total rhinectomy, for part of the nose it is called a partial rhinectomy. Afterwards to cover the defect, a new nose can be made by using another part of the body and/or a nose prosthesis is made.
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| ===Oropharynx===
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| Oropharyngeal cancer begins in the [[oropharynx]], the middle part of the throat that includes the [[soft palate]], the base of the [[tongue]], and the [[tonsil]]s. 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.
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| ===Hypopharynx===
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| 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 [[metastasis|metastasize]] early due to the extensive lymphatic network around the [[larynx]].
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| ===Larynx===
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| [[Laryngeal cancer]] begins in the [[larynx]] or "voice box." Cancer may occur on the [[vocal cords]] 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]].
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| Surgeries can include partial laryngectomy (removal of part of the larynx) and total laryngectomy (removal of the whole larnyx). 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.
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| Also anyone who has had a glossectomy (tongue removal) will be taught to speak again in a new way and have intensive speech therapy
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| ===Trachea===
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| Cancer of the [[Vertebrate trachea|trachea]] is a rare malignancy which can be biologically similar in many ways to head and neck cancer, and is sometimes classified as such.
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| 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 [[teratoma]]s, [[adenocarcinomas]], [[adenoid cystic carcinoma]]s, and [[mucoepidermoid carcinoma]]s. Rarer still are [[melanomas]] and [[lymphomas]] of the upper aerodigestive tract.
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| ==Diagnosis== | | ==Diagnosis== |
| ===Symptoms===
| | [[Head and neck cancer history and symptoms|History & Symptoms]] | [[Head and neck cancer physical examination|Physical Examination]] | [[Head and neck cancer staging|Staging]] | [[Head and neck cancer laboratory tests|Lab Tests]] | [[Head and neck cancer electrocardiogram|Electrocardiogram]] | [[Head and neck cancer chest x ray|Chest X Ray]] | [[Head and neck cancer CT|CT]] | [[Head and neck cancer MRI|MRI]] | [[Head and neck cancer echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Head and neck cancer other imaging findings|Other Imaging Findings]] | [[Head and neck cancer other diagnostic studies|Other Diagnostic Studies]] |
| '''Throat Cancer''' usually begins with symptoms that seem harmless enough, like an enlarged [[lymph node]] on the outside of the neck, a sore throat or a hoarse sounding voice. However, in the case of throat cancer, these conditions may persist and become chronic. There may be a lump or a sore in the throat or neck that does not heal or go away. There may be difficult or painful swallowing. Speaking may become difficult. There may be a persistent earache. Other possible but less common symptoms include some numbness or [[paralysis]] of the face muscles.
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| Presenting symptoms include
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| *Mass in the neck
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| *Neck pain
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| *Weight loss
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| *Bleeding from the mouth
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| *Sinus congestion, especially with [[nasopharyngeal carcinoma]]
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| ===Diagnostic approach===
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| A patient usually presents to the physician complaining of one or more of the above [[symptoms]] The patient will typically undergo a [[needle biopsy]] of this lesion, and a [[histopathologic]] information is available, a multidisciplinary discussion of the optimal treatment strategy will be undertaken between the [[radiation oncologist]], [[surgical oncology|surgical oncologist]], and [[medical oncology|medical oncologist]].
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| ===Histopathology===
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| Throat cancers are classified according to their [[histology]] or cell structure, and are commonly referred to by their location in the oral cavity and neck. This is because where the cancer appears in the throat affects the prognosis - some throat cancers are more aggressive than others depending upon their location. The stage at which the cancer is diagnosed is also a critical factor in the prognosis of throat cancer.
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| ====Squamous Cell Carcinoma====
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| [[Squamous cell]]s are the [[epithelium]] (tissue layer) that is the surface cells of much of the body. [[Skin]] and [[mucous membranes]] are squamous cells. This is the most common form of larynx cancer, accounting for over 90% of throat cancer.<font color=red><sup></sup></font> Squamous Cell Carcinoma is most likely to appear in males over 40 years of age with a history of heavy alcohol use coupled with smoking.
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| ====Epidimoid Cancer====
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| (See [[Squamous cell carcinoma]])
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| ====Adenocarcinoma====
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| [[Adenocarcinoma]] is a cancer of the [[columnar epithelium]] typical of the lower [[esophagus]]. It is typical of Barrett's Esophagus but may be at another location. Adenocarcinoma is thought of as a product of Barrett's Esophagus. | |
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| ==Treatment== | | ==Treatment== |
| ===General considerations===
| | '''Medical therapy:''' [[Head and neck cancer medical therapy#General considerations|General considerations]] | [[Head and neck cancer medical therapy#Radiation therapy|Radiation therapy]] | [[Head and neck cancer medical therapy#Chemotherapy|Chemotherapy]] | [[Head and neck cancer medical therapy#Targeted therapy|Targeted therapy]] |
| 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<ref> {{cite journal |author=Al-Sarraf M |title=Treatment of locally advanced head and neck cancer: historical and critical review |journal=Cancer Control |volume=9 |issue=5 |pages=387-99 |year= |pmid=12410178}}</ref>
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| 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.
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| 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. Survival and recurrence risk has been roughly equivalent between surgical and radiation-based approaches, with a head-to-head comparison in only one randomized study. 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.
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| 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.
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| 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.
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| ===Surgery===
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| [[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.
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| ===Radiation therapy===
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| [[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 [[Metastasis|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.
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| [[Image:radiation-mask.jpg|right|thumb|280px|Radiation mask used in treatment of throat cancer]] | | '''Surgical therapy:''' [[Head and neck cancer surgery#General considerations|General considerations]] | [[Head and neck cancer surgery#Surgery|Surgery]] |
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| ===Chemotherapy===
| | '''Prevention:''' [[Head and neck cancer primary prevention|Primary Prevention]] | [[Head and neck cancer secondary prevention|Secondary Prevention]] |
| [[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.
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| 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.
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| ===Targeted therapy=== | | ==Related chapters== |
| [[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]], and [[erlotinib]].
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| 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.<ref>{{cite journal |author=Bonner J, Harari P, Giralt J, Azarnia N, Shin D, Cohen R, Jones C, Sur R, Raben D, Jassem J, Ove R, Kies M, Baselga J, Youssoufian H, Amellal N, Rowinsky E, Ang K |title=Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck |journal=N Engl J Med |volume=354 |issue=6 |pages=567-78 |year=2006 |pmid=16467544}}</ref> 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.
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| 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.<ref>{{cite journal |author=Burtness B, Goldwasser M, Flood W, Mattar B, Forastiere A |title=Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study |journal=J Clin Oncol |volume=23 |issue=34 |pages=8646-54 |year=2005 |pmid=16314626}}</ref>
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| However, another study which completed in March 2007 found that there was an improvement in survival.
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| 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.
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| 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.
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| 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.
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| 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.)
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| Results
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| 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.
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| 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.
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| [[Erlotinib]] is an oral [[EGFR]] inhibitor, and was found in one [[Clinical trial#Phase II|Phase II clinical trial]] to retard disease progression.<ref>{{cite journal |author=Soulieres D, Senzer N, Vokes E, Hidalgo M, Agarwala S, Siu L |title=Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent or metastatic squamous cell cancer of the head and neck |journal=J Clin Oncol |volume=22 |issue=1 |pages=77-85 |year=2004 |pmid=14701768}}</ref>
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| 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.
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| ==Prognosis==
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| 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.<ref>{{cite journal |author=Gourin C, Podolsky R |title=Racial disparities in patients with head and neck squamous cell carcinoma |journal=Laryngoscope |volume=116 |issue=7 |pages=1093-106 |year=2006 |pmid=16826042}}</ref>
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| 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.
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| Consensus panels in America (American Joint Committee on Cancer AJCC and Europe) 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.<ref>{{cite journal |author=Iro H, Waldfahrer F |title=Evaluation of the newly updated TNM classification of head and neck carcinoma with data from 3247 patients |journal=Cancer |volume=83 |issue=10 |pages=2201-7 |year=1998 |pmid=9827726}}</ref>
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| ===Residual deficits===
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| 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.
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| ===Problem of second primaries===
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| 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%<ref>{{cite journal |author=Jones A, Morar P, Phillips D, Field J, Husband D, Helliwell T |title=Second primary tumors in patients with head and neck squamous cell carcinoma |journal=Cancer |volume=75 |issue=6 |pages=1343-53 |year=1995 |pmid=7882285}}</ref>
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| to 23%<ref>{{cite journal |author=Cooper J, Pajak T, Rubin P, Tupchong L, Brady L, Leibel S, Laramore G, Marcial V, Davis L, Cox J |title=Second malignancies in patients who have head and neck cancer: incidence, effect on survival and implications based on the RTOG experience |journal=Int J Radiat Oncol Biol Phys |volume=17 |issue=3 |pages=449-56 |year=1989 |pmid=2674073}}</ref>
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| 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.
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| Throat cancer has numerous negative effects on the body systems.
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| ===Digestive system===
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| 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 [[choking|choke]] on their food in the early stages of digestion and interfere with the food’s smooth travels down into the [[esophagus]] and beyond.
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| 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.
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| ===Respiratory system===
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| 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 [[lung]]s and interfering with the person’s ability to [[breath]]e; this is even more likely if the patient is a smoker, because they are highly susceptible to [[lung cancer]]. If the respiratory system is unable to bring oxygen into the body, the oxygen deprivation will cause the body's cells to wither and die, causing one to become weaker and sicker.
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| ===Others===
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| Like any [[cancer]], [[metastasize|metastasization]] affects many areas of the body, as the cancer spreads from cell to cell and [[organ (biology)|organ]] to organ. For example, if it spreads to the [[bone marrow]], it will prevent the body from producing enough [[red blood cell]]s and affects the proper functioning of the [[white blood cell]]s 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.
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| ==Prevention==
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| Avoidance of recognised risk factors (as described above)is the single most effective form of prevention. Regular dental examinations may identify pre-cancerous lesions in the oral cavity.
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| It will be interesting to see what effect the widespread use of HPV vaccines has on the incidence of HPV-related H&N cancers.
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| ==References==
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| {{Reflist|2}}
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| ==See also==
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| *[[oral cancer]] | | *[[oral cancer]] |
| *[[cancer of the larynx]] | | *[[cancer of the larynx]] |
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| *Bobby Hamilton - a NASCAR driver who died of head and neck cancer | | *Bobby Hamilton - a NASCAR driver who died of head and neck cancer |
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| ==External links== | | ==Resources== |
| * [http://www.nlm.nih.gov/medlineplus/headandneckcancer.html Head and Neck Cancer - Learn more from MedlinePlus] | | * [http://www.nlm.nih.gov/medlineplus/headandneckcancer.html Head and Neck Cancer - Learn more from MedlinePlus] |
| * [http://www.health.am/cr/head-and-neck-cancer/ Head and Neck Cancer Information] | | * [http://www.health.am/cr/head-and-neck-cancer/ Head and Neck Cancer Information] |
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| {{Tumors}} | | {{Tumors}} |
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