Squamous cell carcinoma (SCC) represents more than 90% of all head and neck cancers. The majority of cancers of the head and neck arise from the surface layers of the upper aerodigestive tract (UAT). UAT cancers include:
- Oral cavity cancers, which include tumours of the buccal mucosa, retromolar triangle, alveolus, hard palate, anterior two thirds of the tongue, floor of the mouth, and the mucosal surface of the lip.
- Cancers of the pharynx:
- Cancers of the oropharynx, which include tumours of the base of the tongue, the tonsil and the under surface of the soft palate.
- Cancers of the hypopharynx (bottom part of the throat), which include tumours of the postcricoid area, pyriform sinus and the posterior pharyngeal wall.
- Cancers of the nasopharynx (behind the nose).
- Cancers of the larynx.
Other UAT sites include the salivary glands, nose, sinuses and middle ear but these cancers are relatively rare. Cancer originating in the nerves and bone of the head and neck is even rarer.
- Head and neck SCC is the sixth most common cancer worldwide, predominantly associated with tobacco use.
- Head and neck cancers are traditionally associated with older men who smoke and consume alcohol. However, the incidence in the younger population of both sexes is rising.
- The incidence of head and neck cancer is relatively low in developed countries and highest in Southeast Asia.
- There are marked regional variations in the incidence of head and neck cancers, with rates ranging from 8 per 100,000 in the Thames and Oxford regions to 13-15 per 100,000 in Wales and in the North Western region.
Heavy smoking, heavy alcohol consumption (the two act synergistically) and poor dentition are the principal risk factors in western countries. The role of alcohol consumption in the development of tongue cancer appears to be independent of cigarette smoking.
- Both incidence and mortality from UAT cancers are higher among socially disadvantaged groups.
- Smoking: smoking is a risk factor for all tumour sites. Leaving a cigarette on the lip is predictive of lip cancer risk irrespective of cumulative tobacco consumption. Chewing tobacco and similar substances (eg, betel quid, which is common in parts of Asia and among some immigrant groups in the UK) is a risk factor for cancer of the oral cavity. A long duration of passive smoking is also a risk factor.
- Alcohol: alcohol consumption strongly increases the risk of developing cancers of the oral cavity, pharynx and larynx. There is a strong relationship between the quantity of alcohol consumption and the level of risk.
- Poor diet is a risk factor for head and neck cancer. Frequent consumption of fruit and vegetables is associated with a reduced risk. Several specific nutritional deficiencies (eg, zinc and vitamin A) may predispose individuals.
- Eating Cantonese-style salted fish increases the risk.
- People with a good Mediterranean diet have less than half the risk of developing oral or pharyngeal cancer and half the risk of developing laryngeal cancer. The key protective elements of the Mediterranean diet include citrus fruit; vegetables (particularly fresh or processed tomatoes), olive oil and fish oils.
- There is evidence to suggest that the presence of gastro-oesophageal reflux disease (GORD) is a risk factor for laryngeal and pharyngeal cancer.
- Genetic factors: there is evidence to suggest a genetic susceptibility to head and neck cancer.
- Human papillomavirus type 16 (HPV16) seropositivity is associated with an increased risk of oral, pharyngeal and laryngeal cancer. The incidence of HPV-related oropharyngeal carcinoma is rising rapidly in developed countries and is easily missed. It has a different presentation and better prognosis than other head and neck cancers.
- Excessive sunlight exposure is associated with melanoma of the lip.
There is no evidence for an effective screening programme for head and neck cancers but dentists should include a full examination of the oral mucosa as part of routine dental check-up.
Other causes of presenting features, including persistent hoarseness, sore throat, cough, earache, neck lumps and mouth lesions.
Refer any patient who presents with symptoms suggestive of head and neck or thyroid cancer to an appropriate specialist or the neck lump clinic, depending on local arrangements. For referrals for patients with possible head and neck cancer, the National Institute for Health and Care Excellence (NICE) recommends:
- Laryngeal cancer: consider a suspected cancer pathway referral (for an appointment within two weeks) for laryngeal cancer in people aged 45 and over with:
- Persistent unexplained hoarseness; or
- An unexplained lump in the neck.
- Oral cancer: consider a suspected cancer pathway referral for oral cancer in people with either:
- Unexplained ulceration in the oral cavity lasting for more than three weeks,
- A persistent and unexplained lump in the neck.
- A red or red and white patch in the oral cavity consistent with erythroplakia or erythroleukoplakia; or
- A lump on the lip or in the oral cavity consistent with oral cancer.
- Thyroid cancer: consider a suspected cancer pathway referral for thyroid cancer in people with an unexplained thyroid lump.
The Scottish Referral Guidelines for Suspected Cancer specify urgent referral for patients meeting the following criteria:
- Unexplained tooth mobility not associated with periodontal disease.
- Persistent, particularly unilateral, discomfort in the throat for more than four weeks.
- Pain on swallowing persisting for three weeks that does not resolve with antibiotics.
- Dysphagia which persists for more than three weeks.
- Stridor (requires same-day referral).
- Unresolved head or neck mass which persists for more than three weeks.
- Unilateral serosanguineous nasal discharge which persists for more than three weeks, particularly with associated symptoms.
- Facial palsy, weakness or severe facial pain or numbness.
- Orbital masses.
With the exception of persistent hoarseness (urgent CXR to decide where to refer), investigations in primary care are not recommended, as they can delay referral.
- 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.
- Other investigations will include a baseline and monitoring of renal function tests, electrolytes, TFTs and pulmonary function tests.
- Diagnosis and staging of head and neck malignancy includes thorough clinical examination by an experienced clinician, fibre-optic endoscopy, fine-needle aspiration (or biopsy) of any neck masses, followed by further examination under anaesthetic, with additional biopsies if needed.
- Biopsy is the only way to establish the diagnosis. Fine-needle aspiration cytology should be used in the investigation of head and neck masses. Lesions that are harder to reach may require endoscopy.
- CT or MRI scanning of the primary tumour site should be performed to help define the spread of the tumour and to stage the neck for nodal metastatic disease. MRI should be used in preference to CT:
- For staging of oropharyngeal and oral tumours.
- For assessment of laryngeal cartilage invasion.
- For the assessment of tumour involvement of the skull base, orbit, cervical spine or neurovascular structures.
- All patients with head and neck cancer should have a CT of the thorax.
- Positron emission tomography (PET) using radioisotope fluorodeoxyglucose (18 F) (FDG-PET) should be performed as the next investigation of choice in patients presenting with:
- Cervical lymph node metastases, where CT or MRI does not demonstrate an obvious primary tumour.
- Suspected recurrent head and neck cancer, where CT/MRI does not demonstrate a clear-cut recurrence.
- Direct pharyngolaryngoscopy and CXR are recommended for patients with SCC of the head and neck, while oesophagoscopy and bronchoscopy might be reserved for patients with associated symptoms.
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 metastases increases and survival decreases. The disease can be classified as:
- Stage I - early disease.
- Stage II - locally advanced disease.
- Stage III - tumour present in lymph nodes.
- Stage IV - metastatic disease.
Patients may also said to be in an unknown stage.
The precise T staging definitions are different for the different tumour sites within the UAT and can be found in the relevant articles (see links above).
T - primary tumour
- Tis - pre-invasive cancer (carcinoma in situ).
- T0 - no evidence of primary tumour.
- 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.
- T4 - tumour with extension to bone, muscle, skin, antrum, neck.
- Tx - minimum requirements to assess primary tumour cannot be met.
N - regional lymph nodes
- N0 - no evidence of regional lymph node involvement.
- N1 - evidence of involvement of a movable homolateral regional lymph node smaller than 3 cm.
- N2a - evidence of involvement of a movable homolateral regional lymph node 3-6 cm.
- N2b - evidence of involvement of multiple homolateral regional lymph nodes smaller than 6 cm.
- N2c - evidence of involvement of contralateral or bilateral regional lymph nodes smaller than 6 cm.
- N3 - any lymph node larger than 6 cm.
- Nx - minimum requirements to assess the regional nodes cannot be met.
M - distant metastases
- M0 - no evidence of distant metastases.
- M1 - evidence of distant metastases.
- Mx - minimum requirements to assess the presence of distant metastases cannot be met.
Lymph node levels
Mainly for the purpose of surgical neck dissection, the lymph nodes of the neck are divided into six areas (called levels):
- I - submental and submandibular triangles.
- II - upper third including the upper jugular and jugulodigastric nodes and the upper posterior cervical nodes.
- III - middle third jugular nodes extending from the carotid bifurcation down to the cricothyroid notch.
- IV - lower jugular nodes extending from the omohyoid muscle down to the clavicle inferiorly.
- V - posterior triangle group of lymph nodes located along the lower half of the spinal accessory nerve and the transverse cervical artery. The supraclavicular nodes are also included in this group.
- VI - anterior compartment group, which comprises lymph nodes surrounding the midline visceral structures of the neck extending from the level of the hyoid bone down to the suprasternal notch.
- Early-stage cancers are usually treated either by surgery or by radiotherapy. More advanced tumours usually require both surgery and chemoradiotherapy.[9, 10]
- Chemotherapy is rarely used alone but chemotherapy used with other treatment modalities has been shown to improve survival in patients curatively treated for non-metastatic head and neck SCC.
- Plastic or reconstructive surgery and specialised dentistry are often needed.
- Patients need considerable help and support with nutrition and communication, both during and after primary treatment.
- Cancers of the head and neck should be managed by specialists as part of a multidisciplinary team, which should include a radiologist, a pathologist, specialist head and neck cancer surgeons (ear, nose and throat; maxillofacial and plastic), a clinical oncologist, a restorative dentist, a clinical nurse specialist, a speech and language therapist and a dietitian.
- The following interventions have been used to reduce or prevent mucositis, which is a common complication of treatment for head and neck cancers: allopurinol, aloe vera, amifostine, cryotherapy, glutamine (intravenous), honey, keratinocyte growth factor, laser, and polymyxin/tobramycin/amphotericin (PTA) antibiotic pastille/paste.
Transoral surgery using the carbon dioxide laser under microscopic guidance is now a widely accepted technique that can help organ preservation, mainly in early disease. Robotic surgery has been used and evaluated, especially for transoral resection of cancers of the base of the tongue and the tonsils.
- Neck dissection techniques:
- Radical neck dissection: all ipsilateral lymph nodes are removed along with the spinal accessory nerve, internal jugular vein and the sternocleidomastoid muscle.
- Modified radical neck dissection: radical neck dissection with preservation of one or more non-lymphatic structures.
- Selective neck dissection: one or more of the lymphatic groups is preserved, based on the patterns of metastases which are predictable for each site of the disease.
- Extended neck dissection: additional lymph node groups or non-lymphatic structures are removed.
- Salvage surgery should be considered in any patient with a resectable local recurrence of oral cavity, oropharyngeal, laryngeal or hypopharyngeal cancer following previous radiotherapy or surgery.
Orofacial reconstruction may be required after removal of orofacial tumours. Various materials are used, including autologous grafts, tissue-engineered bone, or alloplastic materials (such as silicone, titanium or hydroxyapatite). NICE recommends that there is sufficient evidence on efficacy and safety for customised titanium implant insertion for orofacial reconstruction (including reconstruction of the orbital floor, where implants are covered or expected to become substantially covered with soft tissue) to be considered as a management option.
- Altered fractionation radiotherapy improves survival in patients with head and neck SCC. Comparison of the different types of altered radiotherapy suggests that hyperfractionation provides the greatest benefit.
- There is also some evidence that hyperbaric oxygen may improve effectiveness of radiotherapy for cancers of the head and neck.
Management of radiation side-effects
- Patients with oral cavity, laryngeal, oropharyngeal or hypopharyngeal tumours who are being treated with radiotherapy should be offered benzydamine oral rinse before, during and up to three weeks after completion of radiotherapy.
- Pilocarpine may be offered, to improve radiation-induced xerostomia following radiotherapy, to patients with evidence of some intact salivary function, providing there are no medical contradictions.
- There is no evidence to support the use of chemotherapy alone as a curative treatment for SCC of head and neck but chemotherapy is often used in combination with surgery and/or radiotherapy.
- Single-agent cisplatin is recommended as the chemotherapeutic agent of choice in concurrent chemoradiotherapy.
- Neoadjuvant (given in the weeks before surgery or radiotherapy) cisplatin/5-fluorouracil (5FU) followed by radical radiotherapy alone may be used in patients with locally advanced resectable hypopharyngeal cancers who have a complete response to chemotherapy.
- Cetuximab (an anti-epidermal growth factor receptor antibody) in combination with radiotherapy is recommended as a treatment option only for patients with locally advanced SCC of the head and neck whose Karnofsky performance-status score is 90% or greater and for whom all forms of platinum-based chemoradiotherapy treatment are contra-indicated.
- Patients should be seen frequently and regularly within the first three years following treatment.
- Patients with head and neck cancer with dysphagia should receive appropriate speech and language therapy to optimise swallowing function and reduce the risk of aspiration.
- Specialist speech and language therapy should be provided before, during and after chemoradiation treatment, when communication problems are likely to occur and when undergoing laryngectomy to restore voice either by transoesophageal voice prosthesis and/or oesophageal speech.
- All patients with head and neck cancer should be screened at diagnosis for nutritional state. At-risk patients should receive early intervention for nutritional support by an experienced dietician. See also the separate Nutritional Support in Primary Care article.
Management of locoregional recurrence
- In patients with metastatic or locally recurrent head and neck cancer, treatment is usually palliative.
- However, salvage surgery should be considered in any patient with a resectable locoregional recurrence of oral cavity, oropharyngeal, laryngeal or hypopharyngeal cancer following previous radiotherapy or surgery. Selected patients who have unresectable locally recurrent disease following previous radiotherapy may be considered for potentially curative re-irradiation.
- If the recurrence occurs in previously untreated tissues of the head and neck then surgery and chemoradiation may be used as local salvage treatments. If not, then chemotherapy with cisplatin and fluorouracil may be used to reduce symptoms. The addition of cetuximab to cisplatin and fluorouracil has been shown to achieve only a modest benefit for overall survival.
- Because of only modest survival benefit, cetuximab in combination with platinum-based chemotherapy is not recommended by NICE for the treatment of recurrent and/or metastatic SCC of the head and neck.
- Patients with small accessible recurrence in a previously irradiated region may be considered for interstitial brachytherapy in centres with appropriate facilities and expertise.
Palliation of incurable disease
- Patients of adequate performance status should be considered for palliative chemotherapy which may reduce tumour volume. Single-agent methotrexate, single-agent cisplatin or cisplatin/5FU combination should be considered for palliative chemotherapy in patients with head and neck cancer.
- Radiotherapy should be considered for palliative treatment in patients with locally advanced incurable head and neck cancer.
- Appropriate surgical procedures should be considered for palliation of particular symptoms.
- Due to their location, there may also be important practical, social and psychological sequelae - eg, impairment of speech, gastrostomy tube dependence and possible disfigurement.
- Important factors contributing to the quality of life include stage of illness, gastrostomy tube dependence, complication, recurrence and treatment modality.
The main prognostic factors are stage, site of disease, age of the patient and comorbidities.
- Five-year survival rates for patients diagnosed with head and neck cancer in 1996-1999 in England and Wales were:
- Lip: 93%
- Larynx: 65%
- Oral cavity: 51%
- Tongue: 49%
- Oropharynx: 44%
- Hypopharynx: 19%
- Early presentation tends to be associated with good outcomes. However, late presentations are common; treatment in these cases can be particularly demanding and the outlook may be very bleak. As with any type of cancer, the prognosis for individual patients depends heavily on the stage of the disease at presentation.
- There has been little, if any, improvement in survival rates for patients with head and neck cancers over recent decades.
- People who have been treated for UAT cancers remain at high risk, both of developing recurrent disease and of new cancers in the head and neck region and other parts of the body such as the lungs.
- The risk of developing head and neck cancer can be reduced by:
- Not smoking or chewing tobacco.
- Limiting alcohol consumption.
- Increasing the intake of fruit and vegetables (especially tomatoes), olive oil and fish oils.
- Reducing the intake of red meat, fried food and fat.
- High-risk patients should be encouraged to visit the dentist regularly.
- It has been estimated that more than half of all cancers of the mouth, pharynx and larynx in the UK could be prevented by healthy lifestyle changes.
- HPV-related oropharyngeal cancer may theoretically be prevented by vaccination against HPV16, although there is no strong evidence to support this.
Further reading and references
; Squamous cell carcinoma of the head and neck: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2009 May20 Suppl 4:121-2. doi: 10.1093/annonc/mdp149.
; NICE CKS, June 2009 (UK access only)
; NICE Guidance (February 2016)
; Scottish Intercollegiate Guidelines Network - SIGN (2006)
; NICE, November 2004
; Epidemiologic trends in head and neck cancer and aids in diagnosis. Oral Maxillofac Surg Clin North Am. 2014 May26(2):123-41. doi: 10.1016/j.coms.2014.01.001.
; Head and neck cancer--Part 1: Epidemiology, presentation, and prevention. BMJ. 2010 Sep 20341:c4684. doi: 10.1136/bmj.c4684.
; Cancer of the oropharynx. Crit Rev Oncol Hematol. 2002 Jan41(1):107-22.
; Head and neck cancer: changing epidemiology and public health implications. Oncology (Williston Park). 2010 Sep24(10):915-9, 924.
; NICE Clinical Guideline (2015 - last updated July 2017)
; Imaging for Head and Neck Cancer. Surg Oncol Clin N Am. 2015 Jul24(3):455-471. doi: 10.1016/j.soc.2015.03.012. Epub 2015 Apr 16.
; Current management of locally advanced head and neck cancer: the combination of chemotherapy with locoregional treatments. Semin Oncol. 2014 Dec41(6):798-806. doi: 10.1053/j.seminoncol.2014.09.018. Epub 2014 Oct 7.
; Head and neck cancer--Part 2: Treatment and prognostic factors. BMJ. 2010 Sep 28341:c4690. doi: 10.1136/bmj.c4690.
; Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 Radiother Oncol. 2009 Jul92(1):4-14. Epub 2009 May 14.
; Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev. 2011 Apr 13(4):CD000978. doi: 10.1002/14651858.CD000978.pub5.
; NICE Interventional Procedure Guidance, March 2013
; Hyperfractionated or accelerated radiotherapy for head and neck cancer. Cochrane Database Syst Rev. 2010 Dec 812:CD002026.
; Hyperbaric oxygenation for tumour sensitisation to radiotherapy: a systematic Cancer Treat Rev. 2008 Nov34(7):577-91. Epub 2008 Jul 21.
; NICE Technology Appraisal Guidance, June 2008
; NICE Technology Appraisal Guidance, June 2009
; Immediate impact of primary surgery on health-related quality of life of hospitalized patients with oral and oropharyngeal cancer. J Oral Maxillofac Surg. 2008 Jul66(7):1343-50.
; Predictors of quality of life after treatment for oral cavity and oropharyngeal carcinoma. Otolaryngol Head Neck Surg. 2008 Aug139(2):262-7.
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