Home > Oropharyngeal Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI]
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Incidence and Mortality
Estimated new cases and deaths from oropharyngeal cancer (included with oral cavity cancer) in the United States in 2017:
Oropharyngeal cancer is increasing in incidence, which is attributed to the rise in human papilloma virus (HPV)-associated oropharyngeal cancer; it typically occurs in the fifth through seventh decades of life, and men are more than twice as likely as women to have oropharyngeal cancer.[2,3,4]
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 parts:
Regional lymph node anatomy of the head and neck
The regional lymph nodes of the head and neck include the lymph nodes that run parallel to the jugular veins, spinal accessory nerve, and facial artery, and into the submandibular triangle. An understanding of regional anatomy and the status of regional lymph nodes is critical to the care of head and neck cancer patients.[4,6] The regions of the neck are described as levels I to V and retropharyngeal to facilitate communication regarding the lymph node anatomy:
The retropharyngeal lymph nodes are a possible site for nodal spread in oropharyngeal cancer. In a large retrospective cohort from the MD Anderson Cancer Center, the clinical features of 981 oropharyngeal patients who underwent primary radiation therapy were described.[Level of evidence: 3iiA][Level of evidence: 3iiDii]
Risk factors for oropharyngeal squamous cell carcinoma (SCC) include the following:
Refer to the PDQ summary on Oral Cavity and Oropharyngeal Cancer Prevention for more information.
Because of the decreased incidence of smoking in the United States, HPV-negative, smoking-related oropharyngeal cancer is decreasing; however, HPV-positive oropharyngeal cancer is increasing. According to the Surveillance, Epidemiology, and End Results (SEER) program's tissue repository data from 1988 to 2004, the prevalence of HPV-negative cancer declined by 50%, and HPV-positive oropharyngeal cancers increased by 225%.[Level of Evidence: 3iii]
HPV-positive oropharyngeal cancers may represent a distinct disease entity that is causally associated with HPV infection and is also associated with an improved prognosis. Several studies indicate that individuals with HPV-positive tumors have significantly improved survival.[12,15,16,17] In a prospective study involving 253 patients with newly diagnosed or recurrent head and neck SCC, HPV was detected in 25% of the patients. Poor tumor grade and an oropharyngeal site independently increased the probability of the presence of HPV. Oropharyngeal tumors are more likely to be HPV positive (57%) compared with oral cavity (12%) tumor sites and nonoropharyngeal (14%) sites. HPV-positive oropharyngeal cancers predominantly arise in the palatine or lingual tonsils. For tonsil or base-of-tongue sites, 62% of tumors were HPV positive, compared with 25% for other oropharyngeal sites.
Personal history of head and neck cancer
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.[18,19] Because of this risk, patients require lifelong surveillance. Smoking and alcohol consumption after treatment are associated with the development of second primary tumors of the aerodigestive tract.[20,21,22] Patients may need counseling to discontinue smoking and alcohol consumption.
The process of field cancerization may be responsible, in part, for the multiple, synchronous, primary SCCs that occur in oropharyngeal cancer and that are associated with a smoking history. Originally described in 1953, the concept of field cancerization holds that tumors develop in a multifocal fashion within a field of tissue chronically exposed to carcinogens. Molecular studies that detect genetic alterations in histologically normal tissue from high-risk individuals have provided strong support for the concept of field cancerization.[24,25,26,27,28]
A comparison of patients (N = 2,230) with index SCC of the oropharynx site and index SCC of nonoropharyngeal sites (i.e., oral cavity, larynx, and hypopharynx) was performed to determine the likelihood of developing second primary malignancies. The second primary malignancy rate was lower for patients with index oropharyngeal SCC than for patients with index nonoropharyngeal cancer (P < .001). Among patients with oropharyngeal SCC, former smokers had a 50% higher risk of second primary malignancy than never-smokers, and current smokers had a 100% higher risk than never-smokers (P trend = .008). These data suggest that patients who fit the typical HPV phenotype have a very low risk of second-primary malignancy.
The chewing of betel quid, a stimulant preparation commonly used in parts of Asia, increases the risk of oropharyngeal cancer.
Other risk factors
Other risk factors may include the following:
To date, SCC of the oropharynx has not been associated with any specific chromosomal or genetic abnormalities. Genetic and chromosomal aberrations in these cancers are complex.[32,33] 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 of disease progression and may lead to more-definitive therapy.
The clinical presentation of oropharyngeal cancer depends on the tumor's location in the oropharynx. Oropharyngeal cancer may present in the following locations:
The anterior tonsillar pillar and tonsil are the most common location for a primary tumor of the oropharynx. Lesions involving the anterior tonsillar pillar may appear as areas of dysplasia, inflammation, or a superficial spreading lesion. These cancers can spread across a broad region, including the lateral soft palate, retromolar trigone and buccal mucosa, and tonsillar fossa.[4,5] The lymphatic drainage is primarily to level II 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.
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 as advanced-stage disease more often than do cancers of the tonsillar pillar. Approximately 75% of patients will present with stage III or stage IV disease.[4,5] 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.
Signs and symptoms of tonsillar lesions may include the following:[4,5]
Base of the tongue
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 there is significant tumor progression.
Signs and symptoms of advanced base-of-the-tongue cancers may include the following:[4,5]
Lymph node metastasis is common because of the rich lymphatic drainage of the base of the tongue. Approximately 70% or more of patients with advanced base-of-the-tongue cancers have ipsilateral cervical nodal metastases; 30% or fewer of such patients have bilateral, cervical lymph-node metastases.[5,35] The cervical lymph nodes involved commonly include levels II, III, IV, and V and retropharyngeal lymph nodes.
Soft palate tumors are primarily found on the anterior surface. Lesions in this area may remain superficial and in early stages. The lymphatic drainage is primarily to level II nodes.
Pharyngeal wall 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.
Early-stage tumors are often asymptomatic. Tumors of the pharyngeal wall are typically diagnosed in an advanced stage.[4,5]
Signs and symptoms of advanced pharyngeal wall tumors may include the following:
Leukoplakia is 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. Leukoplakia can range from hyperkeratosis to an actual early invasive carcinoma or may represent a fungal infection, lichen planus, or other benign oral disease.
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 presence of tumor must be confirmed histologically. Any other pathologic data obtained from a biopsy and additional radiographic studies are also considered in the diagnosis.
The following procedures may be done to evaluate the primary tumor:
A PET-CT scan yields morphologic and metabolic data to assess the detection of primary tumor, nodal disease, and distant metastatic disease; it may also be used to guide radiation therapy planning. Retrospective data demonstrate that morphologic and PET-glycolytic parameters, which are measured in fluorodeoxyglucose PET-CT, are significantly larger (as measured by Response Evaluation Criteria In Solid Tumors [RECIST] longest diameter); more heterogenous; and have higher standardized uptake value (SUV) max, SUV mean, and metabolic tumor volume in HPV-negative disease compared with HPV-positive disease in the primary tumor for oropharyngeal carcinoma. However, the same PET parameters are frequently larger in the regional nodal disease in patients with HPV-positive disease.[Level of evidence: 3iiDiv]
Prognostic Factors and Survival
Prognostic factors for oropharyngeal carcinoma include the following:
The criteria described in Table 1 are used to determine whether patients have low-, intermediate-, or high-risk oropharyngeal carcinoma; they have been defined by using recursive partitioning analysis in a retrospective analysis of a randomized trial of stage III and IV oropharyngeal SCC patients treated with chemoradiation.
Follow-up After Treatment
A careful examination of the patient's head and neck allows the physician to look for recurrence every 6 to 12 weeks for the first posttreatment year, every 3 months for the second year, every 3 to 4 months for the third year, and every 6 months thereafter.
Other PDQ summaries containing information related to oropharyngeal cancer include the following:
Most oropharyngeal cancers are squamous cell carcinomas (SCCs).[1,2] SCCs may be noninvasive or invasive. For noninvasive SCC, the term carcinoma in situ is used. Histologically, invasive carcinomas are classified as well differentiated, moderately differentiated, poorly differentiated, or undifferentiated. SCCs are usually moderately or poorly differentiated. Grading the deep invasive margins (i.e., invasive front) of SCC may provide better prognostic information than grading the entire tumor. Human papillomavirus (HPV)-positive oropharyngeal cancers arising from the lingual and palatine tonsils are a distinct molecular-pathologic entity that is linked to infection with HPV, especially HPV16. Compared with HPV-negative tumors, HPV-positive tumors are more frequently poorly differentiated and non-keratinizing, and are strongly associated with basaloid morphology and less likely to have TP53 mutations.
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 was histologic grading.
Other types of oropharyngeal cancer include the following:
(Refer to the PDQ summaries on Salivary Gland Cancer Treatment, Adult Hodgkin Lymphoma Treatment, and Adult Non-Hodgkin Lymphoma Treatment for more information.)
The staging system for oropharyngeal cancer is clinical rather than pathological. It is based on the best estimate of the extent of disease before treatment.
Clinical anatomic staging of oropharyngeal cancer involves the following clinical assessment and imaging techniques:
PET has been investigated as an imaging modality for recurrent oropharyngeal cancer.
AJCC Staging Groupings and TNM Definitions
The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define oropharyngeal cancer. Nonepithelial tumors such as those of lymphoid tissue, soft tissue, bone, and cartilage are not included.
An optimal approach for the treatment of oropharyngeal cancer is not easily defined because no single regimen offers a clear-cut, superior-survival advantage. The literature reports various therapeutic options but does not contain reports presenting any valid comparative studies of these options. Treatment considerations should account for functional and performance status including speech and swallowing outcomes.
Surgery and/or Radiation Therapy
Surgery and radiation therapy have been the standards for treatment of oropharyngeal cancer; however, outcome data from randomized trials are limited. Studies have attempted to address the question of whether to use surgery or radiation, but the studies have been underpowered.
Evidence (surgery and/or radiation therapy):
Historically, the posttreatment performance and functional status of patients with base-of-the-tongue primary tumors appeared to be better after radiation therapy than after surgery. Local control and survival are similar in both treatment options.[4,5]
For patients with early-stage disease, single-modality treatment is preferred. Historically, radiation alone has been preferred, although use of new surgical techniques, including transoral surgery and transoral robotic surgery, is increasing. Nonrandomized comparisons of transoral surgery versus primary radiation therapy suggest superior quality of life with minimally invasive surgical techniques. Historically, more-invasive surgical techniques were associated with inferior quality of life and greater morbidity.
A prospective multicenter trial, ECOG-3311 (NCT01898494), evaluating transoral surgery approaches in human papillomavirus-positive oropharyngeal carcinoma with postoperative radiation dose de-escalation is currently under way.
Surgery Followed by Postoperative Radiation Therapy (PORT) With or Without Chemotherapy for Patients With Locally Advanced Disease
New surgical techniques for resection and reconstruction that provide access and functional preservation have extended the surgical options for patients with stage III or stage IV oropharyngeal cancer. Specific surgical procedures and their modifications are not described here because of the wide variety of surgical approaches, the variety of opinions about the role of modified neck dissections, and the multiple reconstructive techniques that may give the same results. This group of patients are managed by head and neck surgeons who are skilled in the multiple procedures available and are actively and frequently involved in the care of these patients.
Depending on pathological findings after primary surgery, PORT with or without chemotherapy is used in the adjuvant setting for the following histological findings:
The addition of chemotherapy to PORT for oropharyngeal SCC demonstrates a locoregional control and overall survival (OS) benefit compared with radiation therapy alone in patients who have high-risk pathological risk factors, extracapsular extension (ECE) of a lymph node, or positive margins, based on a pooled analysis of the EORTC-22931 [NCT00002555] and RTOG-9501 [NCT00002670] studies.[7,8,9,10][Level of evidence: 1iiA]
For patients with intermediate pathological risk factors, the addition of cisplatin chemotherapy given concurrently with PORT is unclear. Intermediate pathologic risk factors include the following:
The addition of cetuximab with radiation therapy in the postoperative setting for these intermediate pathological risk factors is being tested in a randomized trial (RTOG-0920 [NCT00956007]).
A review of published clinical results of radiation therapy for head and neck cancer suggests a significant loss of local control when the administration of radiation therapy was prolonged; therefore, the lengthening of standard treatment schedules is detrimental.[11,12]
Patients who are smokers appear to have lower response rates and shorter survival times than do those who do not smoke while receiving radiation therapy. Counseling patients to stop smoking before beginning radiation therapy may be beneficial.
Intensity-modulated radiation therapy (IMRT) has evolved over the past decade to become a standard technique for head and neck radiation therapy. IMRT allows a dose-painting technique also known as a simultaneous-integrated-boost (SIB) technique with a dose per fraction slightly higher than 2 Gy, which allows slight shortening of overall treatment time and increases the biologically equivalent dose to the tumor.
Evidence (definitive radiation therapy):
The RTOG-0022 study showed high control rates and the feasibility of IMRT at a multi-institutional level; the study also showed high tumor control rates and reduced salivary toxicity compared with previous RTOG studies. However, major target underdose deviations were associated with a higher locoregional failure rate.
Altered fractionation versus standard fractionation
Radiation therapy alone with altered fractionation may be used for patients with locally advanced oropharyngeal cancer who are not candidates for chemotherapy. Altered fractionated radiation therapy yields a higher locoregional control rate compared with standard fractionated radiation therapy for patients with stage III or stage IV oropharyngeal cancer.
Evidence (altered fractionation vs. standard fractionation):
In a long-term analysis, the three investigational arms were compared with SFX.
An additional late effect from radiation therapy is hypothyroidism, which occurs in 30% to 40% of patients who have received external-beam radiation therapy to the entire thyroid gland. Thyroid function testing of patients is considered before therapy and as part of posttreatment follow-up.[24,25]
Prospective data of two randomized controlled trials reported the incidence of hypothyroidism. At a median follow-up of 41 months, 55.1% of the patients developed hypothyroidism (39.3% subclinical, 15.7% biochemical). Patients who underwent IMRT had higher subclinical hypothyroidism (51.1% vs. 27.3%; P = .021), peaking around 1 year after radiation therapy. Younger age, hypopharynx/larynx primary, node positivity, higher dose/fraction (IMRT arm), and D100 were statistically significant factors for developing hypothyroidism.[Level of evidence: 1iiC]
For patients with well-lateralized oropharyngeal cancer, such as a T1 or T2 tonsil primary tumor with limited extension into the palate or tongue base, and limited ipsilateral lymph node involvement without extracapsular extension, elective treatment to the ipsilateral lymph nodes results in only minimal risk of spread to the contralateral neck.  For T3 and T4 tumors that are midline or approach the midline, bilateral nodal treatment is a consideration. In addition to the cervical lymph node chain, retropharyngeal lymph nodes can also be encompassed in the elective nodal treatment.
Concurrent Chemoradiation Therapy
For locally advanced disease, concurrent chemoradiation approaches are superior to radiation therapy alone. This treatment approach emphasizes organ preservation and functionality.[29,30]
Chemoradiation therapy is a standard treatment option for locally advanced (stage III and stage IV) oropharyngeal carcinoma.
Evidence (chemoradiation therapy):
Refer to the PDQ summary on Oral Complications of Chemotherapy and Head/Neck Radiation for more information about oral toxicities.
Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiation Therapy
Three published randomized trials that compared concomitant chemotherapy with induction chemotherapy followed by concomitant chemoradiation for patients with locally advanced head and neck cancer failed to show a survival advantage for induction chemotherapy regimens. The role of induction chemotherapy for patients with oropharyngeal cancer remains unclear.[34,35,36][Level of evidence: 1iA]
Treatment Options for Stage I and Stage II Oropharyngeal Cancer
The management of stage I and stage II carcinomas of the oropharynx requires multidisciplinary input to establish the optimal treatment. Radiation therapy or surgery is equally successful in controlling stage I and stage II oropharyngeal cancer. (Refer to the Treatment Option Overview for Oropharyngeal Cancer section of this summary for more information.)
The choice of treatment is dictated by the anticipated functional speech and swallowing and cosmetic outcome of the treatment options and by the available expertise of the surgeon or radiation oncologist. Treatment is individualized for each patient.
Standard treatment options for stage I and stage II oropharyngeal cancer include the following:
Current Clinical Trials
Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage I oropharyngeal cancer and 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 website.
The management of stage III and stage IV carcinomas of the oropharynx is complex and requires multidisciplinary input to establish the optimal treatment. (Refer to the Treatment Option Overview for Oropharyngeal Cancer section of this summary for more information.)
Treatment Options for Stage III and Stage IV Oropharyngeal Cancer
Treatment options for stage III and stage IV oropharyngeal cancer include the following:
Treatment Options Under Clinical Evaluation for Stage III and Stage IV Oropharyngeal Cancer
Treatment options under clinical evaluation for stage III and stage IV oropharyngeal cancer include the following:
Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage III oropharyngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Treatment Options for Recurrent Oropharyngeal Cancer
The management of recurrent carcinomas of the oropharynx is complex and requires multidisciplinary input to establish the optimal treatment. (Refer to the Treatment Option Overview for Oropharyngeal Cancer section of this summary for more information.)
Treatment options for recurrent oropharyngeal cancer include the following:
Treatment Options Under Clinical Evaluation for Recurrent Oropharyngeal Cancer
Treatment options under clinical evaluation for recurrent oropharyngeal cancer include the following:
Check the list of NCI-supported cancer clinical trials that are now accepting patients with recurrent oropharyngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
This summary was comprehensively reviewed, extensively revised, and reformatted.
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of oropharyngeal cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Oropharyngeal Cancer Treatment are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
PDQ® Adult Treatment Editorial Board. PDQ Oropharyngeal Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/head-and-neck/hp/oropharyngeal-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389168 ]
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Last Revised: 2017-04-21
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