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Oropharyngeal Cancer Treatment (PDQ)

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General Information About Oropharyngeal Cancer
Cellular Classification of Oropharyngeal Cancer
Stage Information for Oropharyngeal Cancer
Treatment Option Overview for Oropharyngeal Cancer
Stage I and Stage II Oropharyngeal Cancer Treatment
Stage III and Stage IV Oropharyngeal Cancer Treatment
Recurrent Oropharyngeal Cancer Treatment
Changes to This Summary (08/14/2017)
About This PDQ Summary

General Information About Oropharyngeal Cancer

Incidence and Mortality

Estimated new cases and deaths from oropharyngeal cancer (included with oral cavity cancer) in the United States in 2017: [1]

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]

Anatomy

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: [5]

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:

Lymph node groups of the neck; drawing shows six groups of lymph nodes in the neck: group IA and IB, group IIA and IIB, group III, group IV, group VA and VB, and group VI.

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. [7][Level of evidence: 3iiA][Level of evidence: 3iiDii]

Risk Factors

Risk factors for oropharyngeal squamous cell carcinoma (SCC) include the following: [8]

Refer to the PDQ summary on Oral Cavity and Oropharyngeal Cancer Prevention for more information.

HPV infection

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%. [14][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. [12] 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. [23] 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. [29]

Betel quid

The chewing of betel quid, a stimulant preparation commonly used in parts of Asia, increases the risk of oropharyngeal cancer. [30]

Other risk factors

Other risk factors may include the following: [8]

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. [34]

Clinical Presentation

The clinical presentation of oropharyngeal cancer depends on the tumor’s location in the oropharynx. Oropharyngeal cancer may present in the following locations:

Tonsil

The anterior tonsillar pillar and tonsil are the most common location for a primary tumor of the oropharynx. [5] 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. [5]

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

Soft palate tumors are primarily found on the anterior surface. [5] Lesions in this area may remain superficial and in early stages. [4] The lymphatic drainage is primarily to level II nodes.

Pharyngeal wall

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

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. [8] Leukoplakia can range from hyperkeratosis to an actual early invasive carcinoma or may represent a fungal infection, lichen planus, or other benign oral disease.

Diagnostic Evaluation

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. [36][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. [17]

Table 1. Characteristics Associated With the Risk of Oropharyngeal Cancera

Degree of RiskCharacteristics3-y OS Rate
LowHPV+, smoking history of ≤10 pack years, and N0–N2a nodal history93% (95% CI, 88.3–97.7)
IntermediateHPV+, smoking history of >10 pack years, and N2b–N3 nodal disease; or 70.8% (95% CI, 60.7–80.8)
HPV-, smoking history of ≤10 pack years, and N2b–N3 nodal disease or T2–T3 tumors
HighHPV- and smoking history >10 pack years; or 46.2% (95% CI, 34.7–57.7)
HPV-, smoking history ≤10 pack years, and T4 disease
CI = confidence interval; HPV = human papillomavirus; OS = overall survival; y = year; + = positive; - = negative. (Refer to the AJCC Staging Groupings and TNM Definitions section of this summary for more information.)
aAng KK, Harris J, Wheeler R, et al.: Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363 (1): 24–35, 2010.

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.

Related Summaries

Other PDQ summaries containing information related to oropharyngeal cancer include the following:

References:

  1. American Cancer Society: Cancer Facts and Figures 2017. Atlanta, Ga: American Cancer Society, 2017. Available online. Last accessed October 13, 2017.
  2. American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society, 2016. Available online. Last accessed July 13, 2017.
  3. Parkin DM, Bray F, Ferlay J, et al.: Estimating the world cancer burden: Globocan 2000. Int J Cancer 94 (2): 153-6, 2001.
  4. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.
  5. Choi WH, Hu KS, Culliney B, et al.: Cancer of the oropharynx. In: Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. 3rd ed. Philadelphia, PA: Lippincott, William & Wilkins, 2009, pp 285-335.
  6. Pharynx. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 41-56.
  7. Gunn GB, Debnam JM, Fuller CD, et al.: The impact of radiographic retropharyngeal adenopathy in oropharyngeal cancer. Cancer 119 (17): 3162-9, 2013.
  8. Neville BW, Day TA: Oral cancer and precancerous lesions. CA Cancer J Clin 52 (4): 195-215, 2002 Jul-Aug.
  9. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.
  10. Licitra L, Bernier J, Grandi C, et al.: Cancer of the oropharynx. Crit Rev Oncol Hematol 41 (1): 107-22, 2002.
  11. Mork J, Lie AK, Glattre E, et al.: Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med 344 (15): 1125-31, 2001.
  12. Gillison ML, Koch WM, Capone RB, et al.: Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92 (9): 709-20, 2000.
  13. D'Souza G, Kreimer AR, Viscidi R, et al.: Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 356 (19): 1944-56, 2007.
  14. Chaturvedi AK, Engels EA, Pfeiffer RM, et al.: Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 29 (32): 4294-301, 2011.
  15. Ringstrm E, Peters E, Hasegawa M, et al.: Human papillomavirus type 16 and squamous cell carcinoma of the head and neck. Clin Cancer Res 8 (10): 3187-92, 2002.
  16. Schwartz SR, Yueh B, McDougall JK, et al.: Human papillomavirus infection and survival in oral squamous cell cancer: a population-based study. Otolaryngol Head Neck Surg 125 (1): 1-9, 2001.
  17. Ang KK, Harris J, Wheeler R, et al.: Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363 (1): 24-35, 2010.
  18. Khuri FR, Lippman SM, Spitz MR, et al.: Molecular epidemiology and retinoid chemoprevention of head and neck cancer. J Natl Cancer Inst 89 (3): 199-211, 1997.
  19. Len X, Quer M, Diez S, et al.: Second neoplasm in patients with head and neck cancer. Head Neck 21 (3): 204-10, 1999.
  20. Do KA, Johnson MM, Doherty DA, et al.: Second primary tumors in patients with upper aerodigestive tract cancers: joint effects of smoking and alcohol (United States). Cancer Causes Control 14 (2): 131-8, 2003.
  21. Khuri FR, Kim ES, Lee JJ, et al.: The impact of smoking status, disease stage, and index tumor site on second primary tumor incidence and tumor recurrence in the head and neck retinoid chemoprevention trial. Cancer Epidemiol Biomarkers Prev 10 (8): 823-9, 2001.
  22. Day GL, Blot WJ, Shore RE, et al.: Second cancers following oral and pharyngeal cancers: role of tobacco and alcohol. J Natl Cancer Inst 86 (2): 131-7, 1994.
  23. Slaughter DP, Southwick HW, Smejkal W: Field cancerization in oral stratified squamous epithelium: clinical implications of multicentric origin. Cancer 6 (5): 963-8, 1953.
  24. Braakhuis BJ, Tabor MP, Leemans CR, et al.: Second primary tumors and field cancerization in oral and oropharyngeal cancer: molecular techniques provide new insights and definitions. Head Neck 24 (2): 198-206, 2002.
  25. Braakhuis BJ, Tabor MP, Kummer JA, et al.: A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications. Cancer Res 63 (8): 1727-30, 2003.
  26. Tabor MP, Brakenhoff RH, van Houten VM, et al.: Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications. Clin Cancer Res 7 (6): 1523-32, 2001.
  27. Tabor MP, Brakenhoff RH, Ruijter-Schippers HJ, et al.: Multiple head and neck tumors frequently originate from a single preneoplastic lesion. Am J Pathol 161 (3): 1051-60, 2002.
  28. Ha PK, Califano JA: The molecular biology of mucosal field cancerization of the head and neck. Crit Rev Oral Biol Med 14 (5): 363-9, 2003.
  29. Gan SJ, Dahlstrom KR, Peck BW, et al.: Incidence and pattern of second primary malignancies in patients with index oropharyngeal cancers versus index nonoropharyngeal head and neck cancers. Cancer 119 (14): 2593-601, 2013.
  30. Ho PS, Ko YC, Yang YH, et al.: The incidence of oropharyngeal cancer in Taiwan: an endemic betel quid chewing area. J Oral Pathol Med 31 (4): 213-9, 2002.
  31. Yokoyama A, Watanabe H, Fukuda H, et al.: Multiple cancers associated with esophageal and oropharyngolaryngeal squamous cell carcinoma and the aldehyde dehydrogenase-2 genotype in male Japanese drinkers. Cancer Epidemiol Biomarkers Prev 11 (9): 895-900, 2002.
  32. Tremmel SC, Gtte K, Popp S, et al.: Intratumoral genomic heterogeneity in advanced head and neck cancer detected by comparative genomic hybridization. Cancer Genet Cytogenet 144 (2): 165-74, 2003.
  33. Brieger J, Jacob R, Riazimand HS, et al.: Chromosomal aberrations in premalignant and malignant squamous epithelium. Cancer Genet Cytogenet 144 (2): 148-55, 2003.
  34. Forastiere A, Koch W, Trotti A, et al.: Head and neck cancer. N Engl J Med 345 (26): 1890-900, 2001.
  35. Lindberg R: Distribution of cervical lymph node metastases from squamous cell carcinoma of the upper respiratory and digestive tracts. Cancer 29 (6): 1446-9, 1972.
  36. Tahari AK, Alluri KC, Quon H, et al.: FDG PET/CT imaging of oropharyngeal squamous cell carcinoma: characteristics of human papillomavirus-positive and -negative tumors. Clin Nucl Med 39 (3): 225-31, 2014.

Cellular Classification of Oropharyngeal Cancer

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. [2] Grading the deep invasive margins (i.e., invasive front) of SCC may provide better prognostic information than grading the entire tumor. [3] 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. [4]

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. [5]

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.)

References:

  1. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.
  2. Oral cavity and oropharynx. In: Rosai J, ed.: Rosai and Ackerman's Surgical Pathology. Vol. 1. 10th ed. New York, NY: Mosby Elsevier, 2011, pp. 237-264.
  3. Bryne M, Boysen M, Alfsen CG, et al.: The invasive front of carcinomas. The most important area for tumour prognosis? Anticancer Res 18 (6B): 4757-64, 1998 Nov-Dec.
  4. Gillison ML, Koch WM, Capone RB, et al.: Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92 (9): 709-20, 2000.
  5. Tabor MP, Braakhuis BJ, van der Wal JE, et al.: Comparative molecular and histological grading of epithelial dysplasia of the oral cavity and the oropharynx. J Pathol 199 (3): 354-60, 2003.

Stage Information for Oropharyngeal Cancer

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. [3]

AJCC Staging Groupings and TNM Definitions

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define oropharyngeal cancer. [2] Nonepithelial tumors such as those of lymphoid tissue, soft tissue, bone, and cartilage are not included.

Table 2. Definitions of TNM Stage 0

StageTNMaDescription
0Tis, N0, M0Tis = Carcinoma in situ.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Pharynx. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 41–56.
The explanations for superscript a is at the end of Table 8.

Table 3. Definitions of TNM Stage I

StageTNMaDescription
IT1, N0, M0T1 = Tumor ≤2 cm in greatest dimension.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Pharynx. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 41–56.
The explanations for superscript a is at the end of Table 8.

Table 4. Definitions of TNM Stage II

StageTNMaDescription
IIT2, N0, M0T2 = Tumor >2 cm but ≤4 cm in greatest dimension.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Pharynx. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 41–56.
The explanations for superscript a is at the end of Table 8.

Table 5. Definitions of TNM Stage III

StageTNMaDescription
IIIT3, N0, M0T3 = Tumor >4 cm in greatest dimension or extension to lingual surface of epiglottis.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
T1, N1, M0T1 = Tumor ≤2 cm in greatest dimension.
N1 = Metastasis in a single ipsilateral lymph node, ≤3 cm in greatest dimension.
M0 = No distant metastasis.
T2, N1, M0T2 = Tumor >2 cm but ≤4 cm in greatest dimension.
N1 = Metastasis in a single ipsilateral lymph node, ≤3 cm in greatest dimension.
M0 = No distant metastasis.
T3, N1, M0T3 = Tumor >4 cm in greatest dimension or extension to lingual surface of epiglottis.
N1 = Metastasis in a single ipsilateral lymph node, ≤3 cm in greatest dimension.
M0 = No distant metastasis.
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Pharynx. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 41–56.
The explanations for superscript a is at the end of Table 8.

Table 6. Definitions of TNM Stage IVA

StageTNMaDescription
IVAT4a, N0, M0T4a = Moderately advanced local disease. Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible.b
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
T4a, N1, M0T4a = Moderately advanced local disease. Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible.b
N1 = Metastasis in a single ipsilateral lymph node, ≤3 cm in greatest dimension.
M0 = No distant metastasis.
T1, N2, M0T1 = Tumor ≤2 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.
M0 = No distant metastasis.
T2, N2, M0T2 = Tumor >2 cm but ≤4 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.
M0 = No distant metastasis.
T3, N2, M0T3 = Tumor >4 cm in greatest dimension or extension to lingual surface of epiglottis.
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.
M0 = No distant metastasis.
T4a, N2, M0T4a = Moderately advanced local disease. Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible.b
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.
M0 = No distant metastasis.
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Pharynx. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 41–56.
The explanations for superscripts a–b are at the end of Table 8.

Table 7. Definitions of TNM Stage IVB

StageTNMaDescription
IVBT4b, Any N, M0T4b = 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.
Any T, N3, M0TX = 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.
N3 = Metastasis in a lymph node >6 cm in greatest dimension.
M0 = No distant metastasis.
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Pharynx. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 41–56.
The explanations for superscripts a–b are at the end of Table 8.

Table 8. Definitions of TNM Stage IVC

StageTNMaDescription
IVCAny T, Any N, M1TX = 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.
M1 = Distant metastasis.
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Pharynx. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 41–56.
aMetastases at level VII are considered regional lymph node metastases.
bMucosal extension to lingual surface of epiglottis from primary tumors of the base of the tongue and vallecula does not constitute invasion of larynx.

References:

  1. Weber AL, Romo L, Hashmi S: Malignant tumors of the oral cavity and oropharynx: clinical, pathologic, and radiologic evaluation. Neuroimaging Clin N Am 13 (3): 443-64, 2003.
  2. Pharynx. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 41-56.
  3. Wong RJ, Lin DT, Schder H, et al.: Diagnostic and prognostic value of [(18)F]fluorodeoxyglucose positron emission tomography for recurrent head and neck squamous cell carcinoma. J Clin Oncol 20 (20): 4199-208, 2002.

Treatment Option Overview for Oropharyngeal Cancer

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.

Table 9. Treatment Options for Oropharyngeal Cancer

Stage (TNM Staging Criteria) Treatment Options
Stage I and stage II oropharyngeal cancerRadiation therapy using standard fractionation
Surgery
Stage III and stage IV oropharyngeal cancerSurgery followed by postoperative radiation therapy (PORT) with or without chemotherapy for patients with locally advanced disease
Radiation therapy using altered fractionation
Concurrent chemoradiation therapy
Neoadjuvant chemotherapy followed by concurrent chemoradiation therapy
Recurrent oropharyngeal cancerSurgical resection, if technically feasible and the tumor does not respond to radiation therapy
Radiation therapy, if the tumor is not completely removed by surgery and curative doses of radiation have not been given previously
A second surgery, if the tumor was not completely removed initially and if technically feasible
Chemotherapy for unresectable locoregionally recurrent disease
Additional radiation therapy using conventionally fractionated radiation therapy, or hyperfractionated radiation therapy with concomitant chemotherapy
Stereotactic body radiotherapy with concurrent cetuximab

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. [1]

Evidence (surgery and/or radiation therapy):

  1. In a prospective randomized trial, 564 head and neck cancer patients with N2 or N3 disease were randomly assigned to either planned neck dissection or surveillance with positron emission tomography–computed tomography (PET/CT) scan. [2]
  2. A pooled analysis of 6,400 patients with base-of-the-tongue oropharyngeal carcinoma from 51 reported series between 1970 and 2000 demonstrated the following: [3]

    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]

  3. In the same study, the results for patients with squamous cell carcinoma (SCC) in the tonsillar region who underwent surgery with or without radiation therapy versus radiation therapy with or without neck dissection were as follows: [3]

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. [6] 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]).

Radiation Therapy

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. [13] 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):

  1. IMRT was studied in a phase II trial (RTOG-0022 [NCT00006360]) of 69 patients with stages T1 to T2, N0 to N1, M0 oropharyngeal carcinoma who were treated with primary radiation therapy without chemotherapy. [14] The median follow-up was 2.8 years. The prescribed planning target volume (PTV) dose to the primary tumor and involved nodes was 66 Gy at 2.2 Gy per fraction over 6 weeks. Subclinical PTVs received simultaneously 54 to 60 Gy at 1.8 to 2.0 Gy per fraction using an SIB technique. The following results were observed:

    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.

  2. Similar nonrandomized multicenter studies used fractionally escalated doses, ranging from 2.3 to 2.5 Gy with IMRT. These doses have been safe when given without concurrent chemotherapy for pharyngolaryngeal T2N0, T2N1, or laryngeal T3N0 SCC. [15] [16] [17] [18] [19]
  3. A randomized trial (PARSPORT [NCT00081029]) conducted in the United Kingdom compared conventional 3-dimensional conformal radiation therapy with IMRT. The following results were observed: [20][Level of evidence: 1iiA]

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):

  1. The randomized trial RTOG-9003 (NCT00771641) included four radiation therapy treatment arms: [21] [22][Level of evidence: 1iiA]

    In a long-term analysis, the three investigational arms were compared with SFX.

  2. The following results were shown in a meta-analysis of 15 randomized trials with a total of 6,515 patients and a median follow-up of 6 years involving the assessment of HFX or AFX-S for patients with stage III and stage IV oropharyngeal cancer: [23][Level of evidence: 1iiA]

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. [26] 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. [26][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. [27] 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. [28] 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):

  1. A meta-analysis of 93 randomized, prospective head and neck cancer trials published between 1965 and 2000 showed the following: [31][Level of evidence: 2A]
  2. In a randomized trial of locally advanced head and neck cancer patients, curative-intent radiation therapy alone (213 patients) was compared with radiation therapy plus weekly cetuximab (211 patients). [32] The initial dose of cetuximab was 400 mg/m2 of body-surface area 1 week before radiation therapy was started, followed by a weekly dose of 250 mg/m2 of body-surface area for the duration of the radiation therapy. This study allowed altered-fractionation regimens to be used in both arms. [32] [33][Level of evidence: 1iiA]

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]

References:

  1. Iyer NG, Tan DS, Tan VK, et al.: Randomized trial comparing surgery and adjuvant radiotherapy versus concurrent chemoradiotherapy in patients with advanced, nonmetastatic squamous cell carcinoma of the head and neck: 10-year update and subset analysis. Cancer 121 (10): 1599-607, 2015.
  2. Mehanna H, Wong WL, McConkey CC, et al.: PET-CT Surveillance versus Neck Dissection in Advanced Head and Neck Cancer. N Engl J Med 374 (15): 1444-54, 2016.
  3. Parsons JT, Mendenhall WM, Stringer SP, et al.: Squamous cell carcinoma of the oropharynx: surgery, radiation therapy, or both. Cancer 94 (11): 2967-80, 2002.
  4. Harrison LB, Zelefsky MJ, Armstrong JG, et al.: Performance status after treatment for squamous cell cancer of the base of tongue--a comparison of primary radiation therapy versus primary surgery. Int J Radiat Oncol Biol Phys 30 (4): 953-7, 1994.
  5. Mendenhall WM, Morris CG, Amdur RJ, et al.: Definitive radiotherapy for squamous cell carcinoma of the base of tongue. Am J Clin Oncol 29 (1): 32-9, 2006.
  6. Chen AM, Daly ME, Luu Q, et al.: Comparison of functional outcomes and quality of life between transoral surgery and definitive chemoradiotherapy for oropharyngeal cancer. Head Neck 37 (3): 381-5, 2015.
  7. Cooper JS, Pajak TF, Forastiere AA, et al.: Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350 (19): 1937-44, 2004.
  8. Bernier J, Domenge C, Ozsahin M, et al.: Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350 (19): 1945-52, 2004.
  9. Bernier J, Cooper JS, Pajak TF, et al.: Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 27 (10): 843-50, 2005.
  10. Cooper JS, Zhang Q, Pajak TF, et al.: Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 84 (5): 1198-205, 2012.
  11. Fowler JF, Lindstrom MJ: Loss of local control with prolongation in radiotherapy. Int J Radiat Oncol Biol Phys 23 (2): 457-67, 1992.
  12. Allal AS, de Pree C, Dulguerov P, et al.: Avoidance of treatment interruption: an unrecognized benefit of accelerated radiotherapy in oropharyngeal carcinomas? Int J Radiat Oncol Biol Phys 45 (1): 41-5, 1999.
  13. Browman GP, Wong G, Hodson I, et al.: Influence of cigarette smoking on the efficacy of radiation therapy in head and neck cancer. N Engl J Med 328 (3): 159-63, 1993.
  14. Eisbruch A, Harris J, Garden AS, et al.: Multi-institutional trial of accelerated hypofractionated intensity-modulated radiation therapy for early-stage oropharyngeal cancer (RTOG 00-22). Int J Radiat Oncol Biol Phys 76 (5): 1333-8, 2010.
  15. Leclerc M, Maingon P, Hamoir M, et al.: A dose escalation study with intensity modulated radiation therapy (IMRT) in T2N0, T2N1, T3N0 squamous cell carcinomas (SCC) of the oropharynx, larynx and hypopharynx using a simultaneous integrated boost (SIB) approach. Radiother Oncol 106 (3): 333-40, 2013.
  16. Buettner F, Miah AB, Gulliford SL, et al.: Novel approaches to improve the therapeutic index of head and neck radiotherapy: an analysis of data from the PARSPORT randomised phase III trial. Radiother Oncol 103 (1): 82-7, 2012.
  17. Gulliford SL, Miah AB, Brennan S, et al.: Dosimetric explanations of fatigue in head and neck radiotherapy: an analysis from the PARSPORT Phase III trial. Radiother Oncol 104 (2): 205-12, 2012.
  18. Kohler RE, Sheets NC, Wheeler SB, et al.: Two-year and lifetime cost-effectiveness of intensity modulated radiation therapy versus 3-dimensional conformal radiation therapy for head-and-neck cancer. Int J Radiat Oncol Biol Phys 87 (4): 683-9, 2013.
  19. Gupta T, Agarwal J, Jain S, et al.: Three-dimensional conformal radiotherapy (3D-CRT) versus intensity modulated radiation therapy (IMRT) in squamous cell carcinoma of the head and neck: a randomized controlled trial. Radiother Oncol 104 (3): 343-8, 2012.
  20. Nutting CM, Morden JP, Harrington KJ, et al.: Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol 12 (2): 127-36, 2011.
  21. Fu KK, Pajak TF, Trotti A, et al.: A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys 48 (1): 7-16, 2000.
  22. Beitler JJ, Zhang Q, Fu KK, et al.: Final results of local-regional control and late toxicity of RTOG 9003: a randomized trial of altered fractionation radiation for locally advanced head and neck cancer. Int J Radiat Oncol Biol Phys 89 (1): 13-20, 2014.
  23. Baujat B, Bourhis J, Blanchard P, et al.: Hyperfractionated or accelerated radiotherapy for head and neck cancer. Cochrane Database Syst Rev (12): CD002026, 2010.
  24. Turner SL, Tiver KW, Boyages SC: Thyroid dysfunction following radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys 31 (2): 279-83, 1995.
  25. Constine LS: What else don't we know about the late effects of radiation in patients treated for head and neck cancer? Int J Radiat Oncol Biol Phys 31 (2): 427-9, 1995.
  26. Murthy V, Narang K, Ghosh-Laskar S, et al.: Hypothyroidism after 3-dimensional conformal radiotherapy and intensity-modulated radiotherapy for head and neck cancers: prospective data from 2 randomized controlled trials. Head Neck 36 (11): 1573-80, 2014.
  27. O'Sullivan B, Warde P, Grice B, et al.: The benefits and pitfalls of ipsilateral radiotherapy in carcinoma of the tonsillar region. Int J Radiat Oncol Biol Phys 51 (2): 332-43, 2001.
  28. Denis F, Garaud P, Bardet E, et al.: Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol 22 (1): 69-76, 2004.
  29. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.
  30. Adelstein DJ: Oropharyngeal cancer: the role of chemotherapy. Curr Treat Options Oncol 4 (1): 3-13, 2003.
  31. Pignon JP, le Matre A, Maillard E, et al.: Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 92 (1): 4-14, 2009.
  32. Bonner JA, Harari PM, Giralt J, et al.: Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354 (6): 567-78, 2006.
  33. Curran D, Giralt J, Harari PM, et al.: Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab. J Clin Oncol 25 (16): 2191-7, 2007.
  34. Haddad R, O'Neill A, Rabinowits G, et al.: Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol 14 (3): 257-64, 2013.
  35. Cohen EE, Karrison TG, Kocherginsky M, et al.: Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer. J Clin Oncol 32 (25): 2735-43, 2014.
  36. Hitt R, Grau JJ, Lpez-Pousa A, et al.: A randomized phase III trial comparing induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as treatment of unresectable head and neck cancer. Ann Oncol 25 (1): 216-25, 2014.

Stage I and Stage II Oropharyngeal Cancer Treatment

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:

  1. Radiation therapy using standard fractionation.
  2. Surgery.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Stage III and Stage IV Oropharyngeal Cancer Treatment

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:

  1. Surgery and postoperative radiation therapy (PORT) with or without chemotherapy for patients with advanced disease. [1] [2] [3] [4][Level of evidence: 1iiA]
  2. Radiation therapy using altered fractionation. [5] [6] [7] [8] [9][Level of evidence: 1iiA]
  3. Concurrent chemoradiation therapy. [10] [11] [12] [13] [14] [15][Level of evidence: 1iiA]
  4. Neoadjuvant chemotherapy followed by concurrent chemoradiation therapy.

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:

  1. Neoadjuvant chemotherapy as given in clinical trials has been used to shrink tumors and render them more definitively treatable with either surgery or radiation. Chemotherapy is given before the other modalities; therefore, the designation neoadjuvant distinguishes it from standard adjuvant therapy, which is given after or during definitive therapy with radiation or after surgery. Many drug combinations have been used in neoadjuvant chemotherapy. [16] [17] [18] [19] [20]
  2. Chemoradiation therapy with immunotherapy. RTOG 3504 (NCT02764593) is evaluating concurrent chemoradiation therapy with nivolumab in patients with intermediate- to high-risk head and neck cancer.
  3. Treatment de-intensification using radiation dose de-escalation is being studied in NRG HN002 (NCT02254278).
  4. Treatment de-intensification using transoral surgery followed by radiation dose de-escalation is being studied in ECOG 3311 (NCT01898494).

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References:

  1. Bernier J, Cooper JS, Pajak TF, et al.: Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 27 (10): 843-50, 2005.
  2. Cooper JS, Zhang Q, Pajak TF, et al.: Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 84 (5): 1198-205, 2012.
  3. Cooper JS, Pajak TF, Forastiere AA, et al.: Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350 (19): 1937-44, 2004.
  4. Bernier J, Domenge C, Ozsahin M, et al.: Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350 (19): 1945-52, 2004.
  5. Horiot JC, Le Fur R, N'Guyen T, et al.: Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomized trial of the EORTC cooperative group of radiotherapy. Radiother Oncol 25 (4): 231-41, 1992.
  6. Bourhis J, Lapeyre M, Tortochaux J, et al.: Phase III randomized trial of very accelerated radiation therapy compared with conventional radiation therapy in squamous cell head and neck cancer: a GORTEC trial. J Clin Oncol 24 (18): 2873-8, 2006.
  7. Overgaard J, Hansen HS, Specht L, et al.: Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomised controlled trial. Lancet 362 (9388): 933-40, 2003.
  8. Overgaard J, Mohanti BK, Begum N, et al.: Five versus six fractions of radiotherapy per week for squamous-cell carcinoma of the head and neck (IAEA-ACC study): a randomised, multicentre trial. Lancet Oncol 11 (6): 553-60, 2010.
  9. Fu KK, Pajak TF, Trotti A, et al.: A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys 48 (1): 7-16, 2000.
  10. Bonner JA, Harari PM, Giralt J, et al.: Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354 (6): 567-78, 2006.
  11. Curran D, Giralt J, Harari PM, et al.: Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab. J Clin Oncol 25 (16): 2191-7, 2007.
  12. Denis F, Garaud P, Bardet E, et al.: Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol 22 (1): 69-76, 2004.
  13. Olmi P, Crispino S, Fallai C, et al.: Locoregionally advanced carcinoma of the oropharynx: conventional radiotherapy vs. accelerated hyperfractionated radiotherapy vs. concomitant radiotherapy and chemotherapy--a multicenter randomized trial. Int J Radiat Oncol Biol Phys 55 (1): 78-92, 2003.
  14. Semrau R, Mueller RP, Stuetzer H, et al.: Efficacy of intensified hyperfractionated and accelerated radiotherapy and concurrent chemotherapy with carboplatin and 5-fluorouracil: updated results of a randomized multicentric trial in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys 64 (5): 1308-16, 2006.
  15. Pignon JP, le Matre A, Maillard E, et al.: Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 92 (1): 4-14, 2009.
  16. Al-Kourainy K, Kish J, Ensley J, et al.: Achievement of superior survival for histologically negative versus histologically positive clinically complete responders to cisplatin combination in patients with locally advanced head and neck cancer. Cancer 59 (2): 233-8, 1987.
  17. Stupp R, Weichselbaum RR, Vokes EE: Combined modality therapy of head and neck cancer. Semin Oncol 21 (3): 349-58, 1994.
  18. Ensley J, Crissman J, Kish J, et al.: The impact of conventional morphologic analysis on response rates and survival in patients with advanced head and neck cancers treated initially with cisplatin-containing combination chemotherapy. Cancer 57 (4): 711-7, 1986.
  19. Pfister DG, Harrison LB, Strong EW, et al.: Organ-function preservation in advanced oropharynx cancer: results with induction chemotherapy and radiation. J Clin Oncol 13 (3): 671-80, 1995.
  20. Dimery IW, Hong WK: Overview of combined modality therapies for head and neck cancer. J Natl Cancer Inst 85 (2): 95-111, 1993.

Recurrent Oropharyngeal Cancer Treatment

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:

  1. Surgical resection, if technically feasible and the tumor does not respond to radiation therapy. [1]
  2. Radiation therapy, if the tumor is not completely removed by surgery and curative doses of radiation have not been given previously. [2]
  3. A second surgery, if the tumor was not completely removed initially and if technically feasible. [1]
  4. Chemotherapy, for unresectable locoregionally recurrent disease.
  5. Additional radiation therapy using conventionally fractionated radiation therapy, or hyperfractionated radiation therapy (HFX) with concomitant chemotherapy. [3]
  6. Stereotactic body radiotherapy with concurrent cetuximab. [4]

Treatment Options Under Clinical Evaluation for Recurrent Oropharyngeal Cancer

Treatment options under clinical evaluation for recurrent oropharyngeal cancer include the following:

  1. Clinical trials evaluating additional radiation therapy using HFX with concomitant chemotherapy, targeted therapy, stereotactic body radiation therapy, or immunotherapy. [5]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References:

  1. Wong LY, Wei WI, Lam LK, et al.: Salvage of recurrent head and neck squamous cell carcinoma after primary curative surgery. Head Neck 25 (11): 953-9, 2003.
  2. Vikram B, Strong EW, Shah JP, et al.: Intraoperative radiotherapy in patients with recurrent head and neck cancer. Am J Surg 150 (4): 485-7, 1985.
  3. Spencer SA, Harris J, Wheeler RH, et al.: RTOG 96-10: reirradiation with concurrent hydroxyurea and 5-fluorouracil in patients with squamous cell cancer of the head and neck. Int J Radiat Oncol Biol Phys 51 (5): 1299-304, 2001.
  4. Vargo JA, Ferris RL, Ohr J, et al.: A prospective phase 2 trial of reirradiation with stereotactic body radiation therapy plus cetuximab in patients with previously irradiated recurrent squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 91 (3): 480-8, 2015.
  5. Tortochaux J, Tao Y, Tournay E, et al.: Randomized phase III trial (GORTEC 98-03) comparing re-irradiation plus chemotherapy versus methotrexate in patients with recurrent or a second primary head and neck squamous cell carcinoma, treated with a palliative intent. Radiother Oncol 100 (1): 70-5, 2011.

Changes to This Summary (08/14/2017)

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.

Editorial changes were made to this summary.

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.

About This PDQ Summary

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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Disclaimer

Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

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Date last modified: 2017-08-14

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Dr. G. Quade
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