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National Cancer Institute
Ultima Vez Modificado: 16 de julio del 2012
Similar to other cancers of the head and neck, tobacco and alcohol abuse represent the most significant risk factors for the development of oropharyngeal cancer. 3 4 (Refer to the PDQ® summaries on Hypopharyngeal Cancer Treatment and Lip and Oral Cavity Cancer Treatment for more information.) Other risk factors may include: 5
Defective elimination of acetaldehyde, a carcinogen generated by alcohol metabolism, poses an additional risk factor for oropharyngeal cancers. In individuals, primarily East Asians, carrying an inactive mutant allele of alcohol dehydrogenase-2, alcohol consumption is associated with a susceptibility to multiple metachronous oropharyngeal cancers that are caused by the decreased elimination of acetaldehyde. 12
Anatomically, the oropharynx is located between the soft palate superiorly and the hyoid bone inferiorly; it is continuous with the oral cavity anteriorly and communicates with the nasopharynx superiorly and the supraglottic larynx and hypopharynx inferiorly. The oropharynx is divided into the following sites: 13
The regional lymph node anatomy of the head and neck contains lymph nodes that run parallel to the jugular veins, spinal accessory nerve, and facial artery and into the submandibular triangle; an understanding of this anatomy and the status of regional lymph nodes is critical to the care of head and neck cancer patients. 3 14 The regions of the neck have been characterized by levels (IV) to facilitate communication regarding the lymph node anatomy:
Histologically, almost all oropharyngeal cancers are squamous cell carcinomas (SCCs). 3 Other cancers in this area include minor salivary gland carcinomas, lymphomas, and lymphoepitheliomas, also known as tonsillar fossa. (Refer to the PDQ® summaries on Salivary Gland Cancer Treatment, Adult Hodgkin Lymphoma Treatment, and Adult Non-Hodgkin Lymphoma Treatment for more information.)
The concept of field cancerization may be responsible in part for the multiple, synchronous primary SCCs that occur in oropharyngeal cancer. This concept, originally described in 1953, proposes that tumors develop in a multifocal fashion within a field of tissue chronically exposed to carcinogens. 15 Molecular studies detecting genetic alterations in histologically normal tissue from high-risk individuals have provided strong support for the field cancerization concept. 16 17 18 19 20
Clinically, cancers of the base of the tongue are insidious. These cancers can grow in either an infiltrative or exophytic pattern. Because the base of the tongue is devoid of pain fibers, these tumors are often asymptomatic until they have progressed significantly. 13
Lymph node metastasis is common because of the rich lymphatic drainage of the base of the tongue. Approximately 70% or more of the patients have ipsilateral cervical nodal metastases; 30% or fewer of the patients have bilateral cervical lymph node metastases. 13 21 The cervical lymph nodes involved commonly include levels II and III.
The anterior tonsillar pillar and tonsil is the most common location for a primary tumor of the oropharynx. 13 Lesions involving the anterior tonsillar pillar may appear as areas of dysplasia, inflammation, or a superficial spreading lesion. These cancers can progress across a broad region including the lateral soft palate, retromolar trigone and buccal mucosa, and tonsillar fossa. 3 13 The lymphatic drainage is primarily to level II nodes.
Lesions of the tonsillar fossa may be either exophytic or ulcerative and have a pattern of extension similar to those of the anterior tonsillar pillar. These tumors present in advanced-stage disease more often than cancers of the tonsillar pillar. Approximately 75% of patients will present with stage III or stage IV disease. 3 13 The lymphatic drainage is primarily to level V nodes. Tumors of the posterior tonsillar pillar can extend inferiorly to involve the pharyngoepiglottic fold and the posterior aspect of the thyroid cartilage. These lesions more frequently involve level V nodes.
These lesions can spread superiorly to involve the nasopharynx, posteriorly to infiltrate the prevertebral fascia, and inferiorly to involve the pyriform sinuses and hypopharyngeal walls. Primary lymphatic drainage is to the retropharyngeal nodes and level II and III nodes. Because most pharyngeal tumors extend past the midline, bilateral cervical metastases are common.
Precancerous lesions of the oropharynx include leukoplakia, erythroplakia, and mixed erythroleukoplakia. 5 These are clinical terms that have no specific histopathologic connotations. 22 Leukoplakia, the most common of the three conditions, is defined by the World Health Organization as a white patch or plaque that cannot be characterized clinically or pathologically as any other disease. 23 The diagnosis of leukoplakia is one of exclusion; conditions such as candidiasis, lichen planus, leukoedema, and others must be ruled out before a diagnosis of leukoplakia can be made. 5
The prevalence of leukoplakia in the United States is decreasing; this decline has been related to a reduction of tobacco consumption. 24 Although erythroplakia is not as common as leukoplakia, it is much more likely to be associated with dysplasia or carcinoma. 5 25
The clinical anatomic staging of oropharyngeal cancers involves both clinical assessment and imaging techniques. 3 14 One study has reported that positron emission tomography scans are more accurate than computed tomographic scans or magnetic resonance imaging in detecting occult nodal disease. 26 Diagnostic methods involve the molecular analysis of tissue from the margins of lip and oral cavity SCCs (i.e., molecular staging) to detect tumor-associated genetic alterations in cells that appear normal by conventional light microscopy. Molecular staging may predict the likelihood of recurrence and may help to establish the relationship between index lesions of SCCs and subsequent lesions. 27 28
Traditionally, surgery and/or radiation therapy have been the standards for treatment of oropharyngeal cancers; these treatment modalities are frequently complicated by suboptimal control of locoregional disease and significant long-term functional deficits. 3 29 Although specific indications for primary surgical resection exist, some investigators suggest that the concurrent use of multiagent chemotherapy and radiation has become the standard of care for the management of patients with late-stage disease, and surgery is often reserved for salvage of those patients who fail definitive nonoperative treatment. 27 29 30 Studies using aggressive and uncompromised radiation therapy with concurrent multiagent chemotherapy have consistently demonstrated a survival and locoregional control benefit. 31 32 33 34 35 This treatment approach emphasizes organ preservation and functionality. New treatments under development include various biologic therapies (i.e., vaccines, growth factor-receptor antagonists, cyclin-dependent kinase inhibitors, oncolytic viruses, and others) and photodynamic therapy. 27 36 37 38 39 40 41 42 43
The rate of curability of cancers of the oropharynx varies depending on the stage and specific site. Local control rates for early base-of-tongue cancers approximate 85%. 3 In a large retrospective study involving 262 patients with base-of-tongue cancer, the overall 5-year disease-specific survival rate for patients with all stages of disease was approximately 50%. Treatment modalities included surgery with and without radiation therapy and radiation therapy alone. None of the treatment modalities had a significant survival advantage either overall or within the stages. 44 45
In a retrospective study involving 162 patients with tonsil carcinoma, 84 patients were treated with primary surgery, which was followed by radiation therapy and/or chemotherapy if histologic signs of aggressive behavior were identified. Survival rates were 89% for stage I, 91% for stage II, 79% for stage III, and 52% for stage IV. 46 In a retrospective study of 188 patients with SCC of the soft palate, uvula, and anterior tonsillar pillar, treatment to the primary site consisted of radiation therapy for 150 patients, surgery for 28 patients, and combined therapy for 10 patients. The overall determinant survival was 80% at 2 years, but it fell to 67% at 5 years. 47 In another retrospective study, 148 patients received definitive radiation therapy for SCC of the pharyngeal wall. Cause-specific survival rates were 89% for stage I, 88% for stage II, 44% for stage III, and 34% for stage IV. Twice-daily fractionation, stage I to stage II disease, and an oropharyngeal primary site were associated with improved locoregional control. 48
HPV-positive oropharyngeal cancers may represent a distinct disease entity that is causally associated with HPV infection and that is also associated with an improved prognosis. Several studies indicate that individuals with HPV-positive tumors have significantly improved survivals. 10 49 50 51 In a prospective study involving 253 patients with newly diagnosed or recurrent head and neck SCC, HPV was detected in 25% of the cases. Poor tumor grade and an oropharyngeal site independently increased the probability of HPV presence. 10
The risk of developing a second primary tumor in patients with tumors of the upper aerodigestive tract has been estimated to be 3% to 7% per year. 52 53 Because of this risk, surveillance of these patients should be lifelong. Patients should be counseled that continued smoking and alcohol consumption after treatment has been associated with the development of second primary tumors of the aerodigestive tract. 54 55 56 (Refer to the PDQ® Smoking Cessation and Continued Risk in Cancer Patients summary for more information.)
To date, SCC of the oropharynx has not been associated with any specific chromosomal or genetic abnormalities. Genetic/chromosomal aberrations in these cancers are complex. 57 58 Despite the lack of specific genetic abnormalities, testing for genetic alterations or ploidy in early oropharyngeal lesions may identify patients who are at the greatest risk for progression and may lead to more definitive therapy. 27
SCCs may be noninvasive or invasive. For noninvasive SCC, the term carcinoma in situ is used. Histologically, invasive carcinomas are well-differentiated, moderately differentiated, poorly differentiated, or undifferentiated. SCCs are usually moderately or poorly differentiated. 2 Grading the deep invasive margins (i.e., invasive front) of SCC may provide better prognostic information than grading of the entire tumor. 3
Immunohistochemical examination of tissues for the expression of the biomarker Ki-67, a proliferation antigen, may complement histologic grading. As a molecular indicator of epithelial dysplasia of the oropharynx, Ki-67 expression appears to correlate well with loss of heterozygosity (LOH) in tumor cells. In a retrospective study involving 43 tissue samples from 25 patients, the assessment of proliferation with Ki-67 was found to be a better surrogate for LOH than histologic grading. 4
Leukoplakia should be used only as a clinically descriptive term meaning that the observer sees a white patch that does not rub off, the significance of which depends on the histologic findings. 5 Leukoplakia can range from hyperkeratosis to an actual early invasive carcinoma or may only represent a fungal infection, lichen planus, or other benign oral disease. (Refer to the General Information About Oropharyngeal Cancer section of this summary for more information.)
Note: The American Joint Committee on Cancer has recently published a new edition of the AJCC Cancer Staging Manual, which includes revisions to the staging for this disease. The PDQ® Adult Treatment Editorial Board, which is responsible for maintaining this summary, is currently reviewing the new staging to determine the changes that need to be made in the summary. In addition to updating this Stage Information section, additional changes may need to be made to other parts of this summary to ensure that it is up-to-date. The changes will be made as soon as possible.
The staging systems for oropharyngeal cancer are all clinical, based on the best possible estimate of the extent of disease before treatment. The assessment of the primary tumor is based on inspection and palpation, when possible, and by indirect mirror examination. The appropriate nodal drainage areas are examined by careful palpation.
The tumor must be confirmed histologically, and any other pathologic data obtained from a biopsy may be included. Additional radiographic studies may be included. As an adjunct to clinical examination, magnetic resonance imaging is used to evaluate the extent of disease in the soft tissues; computed tomography is used to evaluate the mandible and maxilla. 1 Positron emission tomography has been investigated as an imaging modality for recurrent oropharyngeal cancer. 2
Complete endoscopy, typically under general anesthesia, is performed after completion of other staging studies to assess the surface extent of the tumor accurately, to assess deep involvement by palpation for muscle invasion, and to facilitate biopsy. Because of the incidence of multiple primary tumors occurring simultaneously, a careful search for other primary tumors of the upper aerodigestive tract is indicated. 3
The American Joint Committee on Cancer has designated staging by TNM classification to define oropharyngeal cancer. 3 Nonepithelial tumors such as those of lymphoid tissue, soft tissue, bone, and cartilage are not included.
|TX||Primary tumor cannot be assessed.|
|T0||No evidence of primary tumor.|
|Tis||Carcinoma in situ.|
|T1||Tumor 2 cm in greatest dimension.|
|T2||Tumor >2 cm but 4 cm in greatest dimension.|
|T3||Tumor >4 cm in greatest dimension or extension to lingual surface of epiglottis.|
|T4a||Moderately advanced local disease. Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible.b|
|T4b||Very advanced local disease. Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base, or encases carotid artery.|
|NX||Regional lymph nodes cannot be assessed.|
|N0||No regional lymph node metastasis.|
|N1||Metastasis in a single ipsilateral lymph node, 3 cm in greatest dimension.|
|N2||Metastasis in a single ipsilateral lymph node, >3 cm but 6 cm in greatest dimension, or metastasis in multiple ipsilateral lymph nodes, 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, 6 cm in greatest dimension.|
|N2a||Metastasis in a single ipsilateral lymph node >3 cm but 6 cm in greatest dimension.|
|N2b||Metastases in multiple ipsilateral lymph nodes, 6 cm in greatest dimension.|
|N2c||Metastases in bilateral or contralateral lymph nodes, 6 cm in greatest dimension.|
|N3||Metastasis in a lymph node >6 cm in greatest dimension.|
|M0||No distant metastasis.|
|IVC||Any T||Any N||M1|
On attempting to define the optimal therapeutic approach to the oropharynx, it becomes clear that no single therapeutic regimen offers a clear-cut superior survival over other regimens. The literature is filled with reports highlighting various therapeutic options but does not contain reports presenting any valid comparative studies of therapeutic options. The ultimate therapeutic choice will depend on a careful review of each individual case, paying attention to the staging of the neoplasm, the general physical condition of the patient, the emotional status of the patient, the experience of the treating team, and the available treatment facilities.
A review of published, clinical results of radical radiation therapy for head and neck cancer suggests a significant loss of local control when the administration of radiation therapy was prolonged; therefore, lengthening of standard treatment schedules should be avoided whenever possible. 1 2 Patients who smoke during treatment with radiation therapy appear to have lower response rates and shorter survival durations than those who do not; 3 therefore, patients should be counseled to stop smoking before beginning radiation therapy. The posttherapy performance status of patients with base-of-tongue primary tumors appears to be better following radiation therapy than following surgery. Local control and survival is similar in both, which suggests that radiation therapy may be superior. 4 5
Accumulating evidence has demonstrated a high incidence (i.e., >30%40%) of hypothyroidism in patients who have received external-beam radiation therapy to the entire thyroid gland or to the pituitary gland. Thyroid function testing of patients should be considered prior to therapy and as part of posttreatment follow-up. 6 7
Surgery or radiation is equally successful in controlling this stage of oropharyngeal cancer.
When radiation is given, careful choice of radiation technique by a radiation oncologist experienced in managing head and neck cancers is essential. The choice of treatment is dictated by the anticipated functional, cosmetic, and socioeconomic results of the treatment options as well as by the available expertise of the surgeon or radiation therapist. Treatment is individualized for each patient.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I oropharyngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Surgery or radiation is equally successful in controlling this stage of oropharyngeal cancer.
When radiation is given, careful choice of radiation technique by a radiation oncologist experienced in managing head and neck cancers is essential. Interstitial radiation techniques may be used when indicated. The choice of treatment is dictated by the anticipated functional, cosmetic, and socioeconomic results of the treatment options as well as by the available expertise of the surgeon or radiation therapist. Treatment is individualized for each patient.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II oropharyngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
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