Pharyngeal Cancer

Last updated by Peer reviewed by Dr John Cox
Last updated Meets Patient’s editorial guidelines

Added to Saved items
This page has been archived. It has not been updated since 27/07/2015. External links and references may no longer work.
This article is for Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Mouth Cancer (Oral Cancer) article more useful, or one of our other health articles.

Read COVID-19 guidance from NICE

Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.

See also the separate Head and Neck Cancers article.

Cancer of the pharynx is less common than other head and neck cancers. It occurs in three locations:

  • The oropharynx, which includes tumours of the base of tongue, tonsil and the undersurface of the soft palate.[1]
  • The hypopharynx, which includes tumours of the postcricoid area, pyriform sinus and the posterior pharyngeal wall.[1]
  • The nasopharynx, which is behind the nasal cavity and above the soft palate.

Cancers of the oropharynx and hypopharynx are, like oral cancer and cancer of the larynx, usually squamous cell carcinomas (SCCs) which originate in the epithelial cells that line the throat.[2]

Cancer of the nasopharynx has a different aetiology and natural history (and is therefore discussed separately at the end of this article).[3]

  • Pharyngeal cancer is relatively uncommon in England and Wales but higher among those with a South Asian background. Among immigrants from the Indian sub-continent, the risk of death from cancer of the pharynx is five times that of British natives.
  • Oropharyngeal cancer is uncommon and typically affects people aged between 40 and 70 years.[4]
  • There is an increasing incidence of human papillomavirus (HPV)-related SCC, while the incidence of tobacco-related SCC of the oropharynx is decreasing.[5]
  • Nasopharyngeal carcinoma is endemic in Asia and is aetiologically associated with Epstein-Barr virus (EBV).[6]

The symptoms of cancer of the pharynx differ according to the type:

  • Oropharynx: common symptoms are a persistent sore throat, a lump in the mouth or throat, pain in the ear.
  • Hypopharynx: problems with swallowing and ear pain are common symptoms and hoarseness is not uncommon.
  • Nasopharynx: most likely to cause a lump in the neck but may also cause nasal obstruction, deafness and postnasal discharge.

Other symptoms include bleeding causing haemoptysis, halitosis, trismus (suggests involvement of the pterygoid muscles) and weight loss.

See the separate articles on Problems in the Mouth, Oral Ulceration and Salivary Gland Disorders.

It is important to do a full head and neck examination (inspection and palpation) including the mouth. A neck mass or mouth lesion combined with regional pain might suggest a malignant or premalignant process.[7]

  • Any unexplained red or white patches - particularly if these are painful, swollen or bleed easily - should be treated as suspicious until proven otherwise.
  • A mass may be visible.
  • Palpate for nodes. Lymph node metastases generally occur in the upper jugular chain, although they can 'skip' to lower levels and spread. Bilateral metastases are more common with tongue base and soft palate lesions, especially with midline lesions.
  • LFTs may raise suspicions of abdominal metastases (in which case, a CT scan of the abdomen is warranted).
  • CXR will identify pulmonary metastases. An urgent CXR is also warranted in individuals who have an unexplained change in the quality of their voice (hoarse, husky or quiet) for more than three weeks, particularly in smokers and heavy drinkers.
  • Biopsy is the only way to establish the diagnosis. A fine-needle aspiration (FNA) or biopsy may be an alternative for a neck mass; lesions that are harder to reach may require endoscopy.
  • Imaging (CT and MRI) studies should focus on identifying spread: invasion through the pharyngeal constrictors, bony involvement of the pterygoid plates or mandible, invasion of the parapharyngeal space or carotid artery, involvement of the prevertebral fascia and extension into the larynx.

For urgent referrals for suspected cancer, the National Institute for Health and Care Excellence (NICE) recommends:[8]

  • Consider a suspected cancer pathway referral (for an appointment within two weeks) for oral cancer in people with either:
    • Unexplained ulceration in the oral cavity lasting for more than three weeks; or
    • A persistent and unexplained lump in the neck.

90% of all oropharyngeal tumours are SCCs.[3, 9] Other oropharyngeal tumours include adenocarcinomas, lymphomas, sarcomas and melanomas. Pre-cancerous lesions of the oropharynx include leukoplakia, erythroplakia and mixed erythroleukoplakia.[4]

Staging[1]

The 'tumour, nodes, metastases' (TNM) staging system is used for staging head and neck cancers. T is the extent of the primary tumour; N is the involvement of regional lymph nodes; M is the presence of metastases. The depth of infiltration is predictive of prognosis.

T - Primary tumour

Oropharynx:

  • TX - primary tumour cannot be assessed.
  • T0 - no evidence of primary tumour.
  • Tis - pre-invasive cancer (carcinoma in situ).
  • T1 - tumour 2 cm or less in greatest dimension.
  • T2 - tumour larger than 2 cm but not larger than 4 cm.
  • T3 - tumour larger than 4 cm.
  • T4a - larynx, deep/extrinsic muscle of tongue, medial pterygoid, hard palate, mandible.
  • T4b - lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, skull base, carotid artery.

Hypopharynx:

  • TX - primary tumour cannot be assessed.
  • T0 - no evidence of primary tumour.
  • Tis - pre-invasive cancer (carcinoma in situ).
  • T1 - tumour 2 cm or less in greatest dimension and limited to one subsite.
  • T2 - tumour larger than 2 cm but not larger than 4 cm or more than one subsite.
  • T3 - tumour larger than 4 cm or with hemilarynx fixation.
  • T4a - thyroid/cricoid cartilage, hyoid bone, thyroid gland, oesophagus, central compartment soft tissue.
  • T4b - prevertebral facia, carotid artery, mediastinal structures.

The N and M staging definitions are the same for all areas of the upper aerodigestive tract (UAT) and are outlined in the separate Head and Neck Cancers article.

Management[1]

Oropharyngeal cancer
Oropharyngeal malignancies can be treated by surgery (using open or minimally invasive approaches for tumour resection and reconstruction), radiotherapy, chemotherapy, or a combination of these methods.

Surgical resection may include neck dissection to remove lymph nodes. When the malignancy is considered to be unresectable, palliative chemotherapy and radiotherapy can be used.[10]

A Cochrane review found weak evidence that elective neck dissection of clinically negative neck nodes at the time of removal of the primary tumour results in reduced locoregional recurrence. There was insufficient evidence to conclude that elective neck dissection increases overall survival or disease-free survival compared to therapeutic neck dissection. There was no evidence that radical neck dissection increases overall survival compared to conservative neck dissection surgery.[11]

  • Patients with oropharyngeal cancer may be treated by:
    • Primary resection with reconstruction, and selective neck dissection including neck node levels II-IV (or II-V if the base of the tongue is affected); or
    • External beam radiotherapy to include the primary tumour and neck node levels II-IV (or levels II-V if the base of the tongue is affected). Altered fractionation radiotherapy is associated with an improvement in overall survival and locoregional control in patients with oral cavity and oropharyngeal cancers.[12]
    • Transoral carbon dioxide laser surgery:[10]
      • Is a minimally invasive endoscopic approach for treating tumours in the oropharynx.
      • Is usually performed under general anaesthesia, with the tumours visualised using a modified mouth gag and/or an endoscope.
      • Uses the laser beam to excise the tumour completely, together with an adequate margin of tissue around it. Large tumours are removed in two or more pieces.
      • Can be considered, NICE recommends, for the primary treatment of oropharyngeal malignancy.
  • Chemotherapy, in addition to radiotherapy and surgery, is associated with improved overall survival in patients with oral cavity and oropharyngeal cancers.[13]

    (See separate article on Head and Neck Cancers for explanation of node levels)
  • Patients with small accessible tumours may be treated by a combination of external beam radiotherapy and brachytherapy.
  • Prophylactic treatment of the same side of the neck is required for patients with tumours clearly confined to one side of the oropharynx but bilateral treatment of the neck is recommended when the tumour is encroaching on the base of the tongue or soft palate.
  • Postoperative radiotherapy should be considered for patients with a high risk of recurrence.
  • Concurrent cisplatin chemotherapy with postoperative radiotherapy should be considered, especially in patients with extracapsular spread and/or positive surgical margins.
  • Patients with advanced oropharyngeal cancer may be treated by an organ preservation approach:
    • Radiotherapy with concurrent cisplatin chemotherapy.
    • The primary tumour and neck node levels II-IV should be treated bilaterally.
    • In patients medically unsuitable for chemotherapy, concurrent administration of cetuximab with radiotherapy should be considered.
    • Patients with lymph node involvement should be treated with chemoradiotherapy followed by:
      • N1 nodal disease: neck dissection where there is clinical evidence of residual disease following completion of therapy.
      • N2 and N3 nodal disease: planned neck dissection.
    • In patients with a small primary tumour, locally advanced nodal disease may be resected prior to treatment with chemoradiotherapy.

Hypopharyngeal cancer
Patients with early hypopharyngeal cancer may be treated by:

  • Medical external beam radiotherapy with concomitant cisplatin chemotherapy and prophylactic irradiation of neck nodes (levels II-IV bilaterally).
  • Surgical resection which is also a standard management option, whether or not combined with postoperative radiotherapy.[14]Conservative surgery and bilateral selective neck dissection (levels II-IV).
  • Radiotherapy for patients unsuitable for concurrent chemoradiation or surgery.
  • Postoperative radiotherapy - consider for patients with clinical and pathological features that indicate a high risk of recurrence.
  • Concurrent administration of cisplatin with postoperative radiotherapy - consider, especially in patients with extracapsular spread and/or positive surgical margins.

Locally advanced hypopharyngeal cancer:

  • Patients with resectable locally advanced hypopharyngeal cancer may be treated either by:
    • Surgical resection:
      • Postoperative radiotherapy should be considered for patients with clinical and pathological features that indicate a high risk of recurrence.
      • Concurrent cisplatin chemotherapy with postoperative radiotherapy should be considered for patients with extracapsular spread and/or positive surgical margins.
    • An organ preservation approach, with external beam radiotherapy and concurrent cisplatin treatment.
    • Treatment with external beam radiotherapy with concurrent cisplatin chemotherapy for patients with unresectable disease. For patients medically unsuitable for chemotherapy, cetuximab with radiotherapy should be considered.
    • Neoadjuvant cisplatin or 5-fluorouracil (5-FU) followed by radical radiotherapy alone may be used in patients who have a complete response to chemotherapy.

Lymph node involvement:

  • Patients with clinically N0 disease should undergo prophylactic treatment of the neck, either by selective neck dissection or radiotherapy, including bilateral nodal levels II-VI.
  • Patients with clinically node-positive neck disease should be treated by modified radical neck dissection (neck nodal levels II-IV should be included) with postoperative chemotherapy and/or radiotherapy when indicated.
  • In patients with a small primary tumour, locally advanced nodal disease may be resected prior to treating the primary tumour and neck with radiotherapy, with or without chemotherapy.

Complications

  • Surgical resection or contracture after radiotherapy of the soft palate may result in velopharyngeal insufficiency (VPI). This causes nasal regurgitation of liquids and solids and hypernasal speech.
  • Surgical augmentation of the soft palate can be performed or a palatal obturation may be used:
    • With surgical augmentation of the palate, the balance between reducing VPI and causing obstructive sleep apnoea is difficult.
    • A palatal obturator requires cleaning and is not permanent but patients are able to remove them during sleep. For patients who have had the base of the tongue resected, an inferiorly directed palatal obturator assists in achieving contact at the tongue base that is necessary for the projection of food posteriorly during the oral and pharyngeal phases of swallowing.
  • Other complications may include:
    • Hypernasal speech.
    • Dysphagia.[15]
    • Middle-ear effusion (from scarring of the Eustachian tube or loss of function of tensor and/or levator palatini muscles).
  • There is a high incidence of hypothyroidism in patients who have received external beam radiation therapy to the entire thyroid gland or to the pituitary gland.[4]

Prognosis

Five-year survival rates for oropharyngeal cancer depend on the cancer stage but overall five-year survival rates are just above 40%.[9]

Recurrence[16]

  • The risk of recurrence is strongly dependent on the site and stage of the original disease.
  • About 25% of recurrences are asymptomatic and therefore these patients should benefit from close oncological follow-up in the first three years with liberal use of imaging ± endoscopic exploration under anaesthesia.
  • 60% of patients have recurrence by two years and 80% by three years.

Mortality

  • The outlook for these patients has improved over the past couple of decades.
  • The survival depends heavily on the stage of the disease at presentation but the overall survival rate at five years is about 55% and 41% at 10 years.[3]
  • When considering all the different forms of orolaryngeal cancers together, the two-year survival rate is 89.7% for stage I and 48.6% for stage IV.

Nasopharyngeal cancer most often occurs within the lateral nasopharyngeal recess. Nasopharyngeal cancer may be well-differentiated, moderately-differentiated or undifferentiated. The undifferentiated form is the most common and is the most strongly associated with EBV infection.

Sinonasal malignant neoplasms are rare tumours that constitute about 3% of tumours in the upper respiratory tract. Only a fraction of these arise in the nasal cavity.

Epidemiology

  • Nasopharyngeal carcinoma is a prevalent malignancy in Southeast Asia (including China, Hong Kong, Singapore, Malaysia and Taiwan) and also in Alaska, Greenland and Tunisia.
  • Nasopharyngeal carcinoma is relatively uncommon in western countries.
  • Although reported in all age groups, the peak incidence appears to occur in those aged 30-40 years and 50-60 years.
  • Nasopharyngeal carcinoma is more common in males, with a male:female ratio of 3:1.

Risk factors[17]

Unlike other SCCs of the head and neck, nasopharyngeal cancer does not appear to be linked to excess use of tobacco or moderate alcohol intake. Factors thought to predispose to nasopharyngeal carcinoma include:

  • Chinese (or Asian) ancestry.
  • EBV exposure.
  • Heavy alcohol intake.

Presentation

  • Nasopharyngeal carcinoma often presents at a late stage of disease.
  • Initial nonspecific symptoms may include nasal obstruction, blood-tinged sputum or nasal discharge, tinnitus, sore throat, headache, ear fullness and unilateral conductive hearing loss from serous otitis media or recurrent acute otitis media.
  • In advanced disease, the tumour may invade the skull and spread intracranially.
  • Cranial nerve involvement (usually II-VI or IX-XII), including diplopia and numbness of the face, suggests cavernous sinus invasion.
  • Nasopharyngeal cancer spreads readily to the lymph nodes in the neck and over half of patients either present with an enlarged mass in the neck or are found to have cervical metastasis at the time of diagnosis. The enlarged lymph nodes are often painless, bilateral and posterior.
  • Distant metastases occur more often than in other head and neck cancers and are present in 5-10% of patients at the initial presentation. The most frequent sites for metastases are bone, lung, and liver.

Investigations[17]

  • Diagnosis is made by biopsy of the nasopharyngeal mass. FNA of a neck mass may be useful for the detection of an occult nasopharyngeal primary tumour. Workup includes:
    • Careful visual examination (by mirror or endoscope), evaluation of neck nodes, evaluation of cranial nerve function and hearing.
    • Skull X-rays (especially base-of-skull views) to evaluate neural foramina. CXR. FBC, renal function tests and electrolytes.
    • Complete CT scan or MRI scan with views delineating the upper and lower extent of the lesion.
  • In the patient who presents with only cervical adenopathy, the finding of EBV genomic material in the tissue after amplification of DNA with the polymerase chain reaction (PCR) lends strong evidence for a nasopharyngeal primary tumour.
  • Any clinical or laboratory suggestion of distant metastasis may prompt further evaluation of other sites. Careful dental and oral hygiene evaluation and therapy are particularly important prior to initiation of radiation treatment. MRI is often more helpful than CT scans in detecting abnormalities and in defining their extent.
  • Positron emission tomography (PET) using radioisotope fluorodeoxyglucose (18 F) (FDG-PET) has been shown to be more sensitive and specific than CT scan in assessing for distant metastasis to lungs, liver and bones. PET scans may also be useful in planning treatment for patients with suspected recurrence.

Staging[18]

The 'tumour, nodes, metastases' (TNM) staging system is used for staging head and neck cancers. T is the extent of the primary tumour; N is the involvement of regional lymph nodes; M is the presence of metastases. The depth of infiltration is predictive of prognosis. With increasing depth of invasion of the primary tumour, the risk of nodal metastasis increases and survival decreases.

T - Primary tumour

  • TX - primary tumour cannot be assessed.
  • T0 - no evidence of primary tumour.
  • Tis - carcinoma in situ.
  • T1 - tumour confined to the nasopharynx.
  • T2 - tumour extends to the soft tissues of the oropharynx and/or the nasal fossa:
    • T2a - without parapharyngeal extension.
    • T2b - with parapharyngeal extension.
  • T3 - tumour invades the bony structures and/or the paranasal sinuses.
  • T4 - tumour with intracranial extension and/or involvement of cranial nerves, infratemporal fossa, hypopharynx, orbit, or masticator space.

N - regional lymph nodes

  • NX - regional lymph nodes cannot be assessed.
  • N0 - no regional lymph node metastasis.
  • N1 - unilateral metastasis in lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa.
  • N2 - bilateral metastasis in lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa.
  • N3 - metastasis in lymph node(s):
    • N3a - greater than 6 cm in dimension.
    • N3b - extension to the supraclavicular fossa.

Distant metastasis

  • MX - distant metastasis cannot be assessed.
  • M0 - no distant metastasis.
  • M1 - distant metastasis.

Stage

  • Stage I - T1, N0, M0.
  • Stage IIA - T2a, N0, M0.
  • Stage IIB - T1/T2a, N1, M0; T2b, N0/N1, M0.
  • Stage III - T1/T2a/T2b, N2, M0; T3, N0/N1/N2, M0.
  • Stage IVA - T4, N0/N1/N2, M0.
  • Stage IVB - any T, N3, M0.
  • Stage IVC - any T, any N, M1.

Management

  • External beam radiation therapy is the primary mode of therapy for previously untreated nasopharyngeal carcinoma.
  • Chemotherapy as an adjunct to radiotherapy has been shown to result in a small but significant improvement in survival for patients with locally advanced nasopharyngeal carcinoma compared with radiotherapy alone.[19] Chemotherapy can be delivered before (neoadjuvant), during (concurrent), or following (adjuvant) radiation therapy. Active chemotherapeutic agents include cisplatin, 5-FU, doxorubicin, epirubicin, bleomycin, mitoxantrone, methotrexate, and vinca alkaloids.
  • Salvage nasopharyngectomy and neck dissection may be indicated in patients with nasopharyngeal carcinoma that persists or recurs following prior treatment with radiation with or without chemotherapy.
  • Salvage nasopharyngectomy is sometimes used for the treatment of recurrent disease.
  • For patients with distant metastases, there is no curative treatment and palliative care is directed toward pain relief, symptom control and prolongation of life. Radiation can be very effective in controlling pain from bone metastasis.
  • Monitoring of patients should include thorough examination of the head and neck for any risk of recurrence, surveillance of thyroid function and pituitary function, regular check of dental and oral hygiene, jaw exercises to avoid trismus, evaluation of cranial nerve function, and evaluation of systemic complaints to identify distant metastasis.

Prognosis

  • Unlike other head and neck carcinomas, some nasopharyngeal carcinomas have a long, protracted course and some patients can live for many years.
  • During the past decades, the overall five-year survival rate has improved from 60% to 80%. However, 20-30% patients finally progress with distant metastasis and/or loco-regional recurrence.[18]

Are you protected against flu?

See if you are eligible for a free NHS flu jab today.

Check now

Further reading and references

  1. Diagnosis and management of head and neck cancer; Scottish Intercollegiate Guidelines Network - SIGN (2006)

  2. Moyer VA; Screening for oral cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014 Jan 7160(1):55-60. doi: 10.7326/M13-2568.

  3. Service guidance on improving outcomes in head and neck cancers; NICE, November 2004 (checked June 2015).

  4. General Information About Oropharyngeal Cancer; National Cancer Institute

  5. Pytynia KB, Dahlstrom KR, Sturgis EM; Epidemiology of HPV-associated oropharyngeal cancer. Oral Oncol. 2014 May50(5):380-6. doi: 10.1016/j.oraloncology.2013.12.019. Epub 2014 Jan 22.

  6. Zhang L, Chen QY, Liu H, et al; Emerging treatment options for nasopharyngeal carcinoma. Drug Des Devel Ther. 20137:37-52. doi: 10.2147/DDDT.S30753. Epub 2013 Feb 1.

  7. Epstein JB, Gorsky M, Cabay RJ, et al; Screening for and diagnosis of oral premalignant lesions and oropharyngeal squamous cell carcinoma: role of primary care physicians. Can Fam Physician. 2008 Jun54(6):870-5.

  8. Suspected cancer: recognition and referral; NICE guideline (2015 - last updated October 2023)

  9. Mouth and oropharyngeal cancer; Cancer Research UK

  10. Transoral carbon dioxide laser surgery for primary treatment of oropharyngeal malignancy; NICE Interventional Procedure Guidance, March 2014

  11. Bessell A, Glenny AM, Furness S, et al; Interventions for the treatment of oral and oropharyngeal cancers: surgical treatment. Cochrane Database Syst Rev. 2011 Sep 7(9):CD006205. doi: 10.1002/14651858.CD006205.pub3.

  12. Glenny AM, Furness S, Worthington HV, et al; Interventions for the treatment of oral cavity and oropharyngeal cancer: radiotherapy. Cochrane Database Syst Rev. 2010 Dec 812:CD006387.

  13. Furness S, Glenny AM, Worthington HV, et al; Interventions for the treatment of oral cavity and oropharyngeal cancer: chemotherapy. Cochrane Database Syst Rev. 2011 Apr 13(4):CD006386. doi: 10.1002/14651858.CD006386.pub3.

  14. Mura F, Bertino G, Occhini A, et al; Surgical treatment of hypopharyngeal cancer: a review of the literature and proposal for a decisional flow-chart. Acta Otorhinolaryngol Ital. 2013 Oct33(5):299-306.

  15. Greven KM, White DR, Browne JD, et al; Swallowing dysfunction is a common sequelae after chemoradiation for oropharynx carcinoma. Am J Clin Oncol. 2008 Jun31(3):209-12.

  16. Sesterhenn AM, Muller HH, Wiegand S, et al; Cancer of the oro- and hypopharynx - when to expect recurrences? Acta Otolaryngol. 2008 Aug128(8):925-9.

  17. Head and Neck Cancer; National Cancer Institute

  18. Li J, Zou X, Wu YL, et al; A comparison between the sixth and seventh editions of the UICC/AJCC staging system for nasopharyngeal carcinoma in a Chinese cohort. PLoS One. 2014 Dec 239(12):e116261. doi: 10.1371/journal.pone.0116261. eCollection 2014.

  19. Baujat B, Audry H, Bourhis J, et al; Chemotherapy as an adjunct to radiotherapy in locally advanced nasopharyngeal Cochrane Database Syst Rev. 2006 Oct 18(4):CD004329.

newnav-downnewnav-up