Oropharyngeal Cancer Treatment (Adult) (PDQ®)–Health Professional Version

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 2018:[1]

  • New cases: 51,540.
  • Deaths: 10,030.

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.[1-3]


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:[4]

  • Base of the tongue, which includes the pharyngoepiglottic folds and the glossoepiglottic folds.
  • Vallecula.
  • Tonsillar region, which includes the fossa and the anterior and posterior pillars.
  • Soft palate, which includes the uvula.
  • Posterior and lateral pharyngeal walls.

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.[3,5] The regions of the neck are described as levels I to V and retropharyngeal to facilitate communication regarding the lymph node anatomy:

  • Level I contains the submental and submandibular lymph nodes.
  • Level II contains the upper jugular lymph nodes, which are above the digastric muscle.
  • Level III contains the mid-jugular lymph nodes, which are between the omohyoid muscle and the digastric muscle.
  • Level IV contains the lower jugular lymph nodes.
  • Level V contains the lymph nodes of the posterior triangle.
  • Retropharyngeal lymph nodes.
ENLARGELymph 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.[6][Level of evidence: 3iiA][Level of evidence: 3iiDii]

  • The base of the tongue (47%) and the tonsil (46%) were the most common primary sites.
  • Most patients had stage T1 to T2 primary tumors (64%) and stage III to IVB disease (94%).
  • The incidence of radiographic retropharyngeal-node involvement was 10% and was highest for the pharyngeal wall (23%) and lowest for the base of the tongue (6%).
  • Retropharyngeal lymph-node involvement was associated with inferior 5-year local control and inferior recurrence-free survival, distant metastases–free survival, and overall survival on multivariate analysis.

Risk Factors

Risk factors for oropharyngeal squamous cell carcinoma (SCC) include the following:[7]

  • Smoking history of more than 10 pack years and other tobacco use.[8,9]
  • Heavy alcohol use.
  • HPV, especially HPV type16, also known as HPV-16.[10-12]
  • Personal history of head and neck cancer.
  • Betel quid chewing.

Refer to the PDQ summary on Oral Cavity, Pharyngeal, and Laryngeal 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%.[13][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.[11,14-16] 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.[11] 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.[17,18] 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.[19-21] 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.[22] Molecular studies that detect genetic alterations in histologically normal tissue from high-risk individuals have provided strong support for the concept of field cancerization.[23-27]

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 (< .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.[28]

Betel quid

The chewing of betel quid, a stimulant preparation commonly used in parts of Asia, increases the risk of oropharyngeal cancer.[29]

Other risk factors

Other risk factors may include the following:[7]

  • Defective elimination of acetaldehyde, a carcinogen generated by alcohol metabolism. In individuals, primarily East Asians, who carry an inactive mutant allele of alcohol dehydrogenase-2, alcohol consumption is associated with a susceptibility to multiple metachronous oropharyngeal cancers that are caused by the decreased elimination of acetaldehyde.[30]

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.[31,32] 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.[33]

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, tonsillar fossa, tonsillar pillars, or glossotonsillar sulci.
  • Base of the tongue (posterior 1/3 of tongue posterior to circumvallate papillae).
  • Vallecula.
  • Soft palate, inferior surface, or uvula.
  • Posterior pharyngeal wall.


The anterior tonsillar pillar and tonsil are the most common location for a primary tumor of the oropharynx.[4] 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.[3,4] 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.[3,4] 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:[3,4]

  • Pain.
  • Dysphagia.
  • Weight loss.
  • Ipsilateral referred otalgia.
  • A mass in the neck.

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.[4]

Signs and symptoms of advanced base-of-the-tongue cancers may include the following:[3,4]

  • Pain.
  • Dysphagia.
  • Weight loss.
  • Referred otalgia secondary to cranial nerve involvement.
  • Trismus secondary to pterygoid muscle involvement.
  • Fixation of the tongue that is caused by infiltration of the deep muscle.
  • A mass in the neck.

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.[4,34] 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.[4] Lesions in this area may remain superficial and in early stages.[3] 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.[3,4]

Signs and symptoms of advanced pharyngeal wall tumors may include the following:

  • Pain.
  • Bleeding.
  • Dysphagia.
  • Weight loss.
  • A mass in the neck.


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.[7] 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:

  • Positron emission tomography–computed tomography scan (PET-CT) scan.
  • Magnetic resonance imaging.
  • Endoscopy.
  • Laryngoscopy.
  • Biopsy and p16 testing to assess for HPV status.

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.[35][Level of evidence: 3iiDiv]

Prognostic Factors and Survival

Prognostic factors for oropharyngeal carcinoma include the following:

  • HPV status.
  • Smoking history (pack-year smoking history of 10 or more years).
  • Tumor stage and nodal status.

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.[16]

Table 1. Characteristics Associated With the Risk of Oropharyngeal Cancera
Degree of Risk Characteristics 3-y OS Rate
CI = confidence interval; HPV = human papillomavirus; OS = overall survival; + = 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.
Low HPV+, smoking history of ≤10 pack years, and N0–N2a nodal history 93% (95% CI, 88.3–97.7)
Intermediate HPV+, 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
High HPV- and smoking history >10 pack years; or 46.2% (95% CI, 34.7–57.7)
HPV-, smoking history ≤10 pack years, and T4 disease

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:

  1. American Cancer Society: Cancer Facts and Figures 2018. Atlanta, Ga: American Cancer Society, 2018. Available online. Last accessed August 3, 2018.
  2. Parkin DM, Bray F, Ferlay J, et al.: Estimating the world cancer burden: Globocan 2000. Int J Cancer 94 (2): 153-6, 2001. [PUBMED Abstract]
  3. 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.
  4. 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.
  5. 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.
  6. Gunn GB, Debnam JM, Fuller CD, et al.: The impact of radiographic retropharyngeal adenopathy in oropharyngeal cancer. Cancer 119 (17): 3162-9, 2013. [PUBMED Abstract]
  7. Neville BW, Day TA: Oral cancer and precancerous lesions. CA Cancer J Clin 52 (4): 195-215, 2002 Jul-Aug. [PUBMED Abstract]
  8. 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.
  9. Licitra L, Bernier J, Grandi C, et al.: Cancer of the oropharynx. Crit Rev Oncol Hematol 41 (1): 107-22, 2002. [PUBMED Abstract]
  10. 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. [PUBMED Abstract]
  11. 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. [PUBMED Abstract]
  12. 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. [PUBMED Abstract]
  13. 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. [PUBMED Abstract]
  14. Ringström 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. [PUBMED Abstract]
  15. 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. [PUBMED Abstract]
  16. 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. [PUBMED Abstract]
  17. 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. [PUBMED Abstract]
  18. León X, Quer M, Diez S, et al.: Second neoplasm in patients with head and neck cancer. Head Neck 21 (3): 204-10, 1999. [PUBMED Abstract]
  19. 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. [PUBMED Abstract]
  20. 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. [PUBMED Abstract]
  21. 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. [PUBMED Abstract]
  22. Slaughter DP, Southwick HW, Smejkal W: Field cancerization in oral stratified squamous epithelium: clinical implications of multicentric origin. Cancer 6 (5): 963-8, 1953. [PUBMED Abstract]
  23. 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. [PUBMED Abstract]
  24. 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. [PUBMED Abstract]
  25. 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. [PUBMED Abstract]
  26. 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. [PUBMED Abstract]
  27. 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. [PUBMED Abstract]
  28. 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. [PUBMED Abstract]
  29. 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. [PUBMED Abstract]
  30. 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. [PUBMED Abstract]
  31. Tremmel SC, Götte 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. [PUBMED Abstract]
  32. Brieger J, Jacob R, Riazimand HS, et al.: Chromosomal aberrations in premalignant and malignant squamous epithelium. Cancer Genet Cytogenet 144 (2): 148-55, 2003. [PUBMED Abstract]
  33. Forastiere A, Koch W, Trotti A, et al.: Head and neck cancer. N Engl J Med 345 (26): 1890-900, 2001. [PUBMED Abstract]
  34. 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. [PUBMED Abstract]
  35. 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. [PUBMED Abstract]