Cancers of the Oral Cavity

Authored by , Reviewed by Dr John Cox | Last edited | Meets Patient’s editorial guidelines

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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.

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See also the separate Head and Neck Cancers article.

Most cancers of the oral cavity and pharynx are squamous cell carcinomas (SCCs)[1]. About one third of oral cancers are diagnosed in the mouth cavity and a similar proportion on the tongue[2]. Lip cancer is the least frequent type of oral cancer. Oral cavity cancer includes tumours of the[3]:

  • Buccal mucosa.
  • Retromolar triangle.
  • Alveolus.
  • Hard palate.
  • Anterior two thirds of the tongue.
  • Floor of the mouth.
  • Mucosal surface of the lip.

Oral mucosal melanomas may occur, particularly affecting the palate, alveolar gingivae and lips. Virtually any malignancy can metastasise to the oral cavity but carcinomas of the breast, lung, kidney and adrenal gland are the most common.

Early detection and treatment are critical, as they increase survival chances considerably, allow for simpler treatment and result in a better quality of life for survivors.

  • Around 6,800 people (4,510 men and 2,257 women) were diagnosed with oral cancer in 2011 in the UK (incidence 9 per 100,000).
  • One fifth of oral cancer cases diagnosed in the UK occur in people aged 75 and over. The 50-74 age group contributes around 7 in 10 male oral cancer cases and around 6 in 10 female cases.
  • Oral cancer incidence rates in the UK have risen by a third in the last decade.
  • Worldwide, more than 300,000 new cases of lip and oral cavity cancer were estimated to have been diagnosed in 2012, with incidence rates varying across the world.
  • In India the incidence rate approaches 50% of all cancers. In Europe the incidence of oral cavity cancer is very low, accounting for less than 5% of all cancers; However, in France, it is the third most common cancer in males and the second most common cause of death from cancer.

Risk factors

Heavy smoking (or chewing tobacco products), heavy alcohol consumption and poor dentition are the principal risk factors in western countries.

Smoking is the main avoidable risk factor for oral cancer, linked to an estimated 65% of oral cancer cases in the UK. An estimated 91% of oral cancers in the UK are linked to lifestyle factors, including smoking, alcohol (30%) and infections (13%). Betel quid, smokeless tobacco, ionising radiation and certain occupational exposures also cause oral cancer[4].

  • There is increasing evidence which shows that oral sex can be a contributory factor in passing on the disease, via the transmission of the human papillomavirus (HPV) which can be found in the lining of the mouth and throat, the cervix and the anus. HPV has been detected in various amounts in persons with oral dysplasia, leukoplakia and malignancy[5].
  • Paterson Brown-Kelly syndrome (Plummer-Vinson syndrome), which includes iron deficiency, has been associated with an increased risk of cancer of the oral cavity. Increasing amounts of data suggest that vitamins A and C, along with the carotenoids, may be protective against epithelial cancers.
  • Excessive sunlight exposure is associated with melanoma of the lip.

November 2017 - Dr Hayley Willacy recently read a meta-analysis published in PLoS One suggesting Epstein-Barr virus (EBV) infection significantly increases the risk for oral squamous cell carcinoma (OSCC)[6]. EBV-associated malignancies may be mediated by viral proteins which regulate cell proliferation, apoptosis and immune response. A pooled analysis of 13 studies showed a significant association between EBV infection and risk for OSCC, but the heterogeneity among studies was high. Sensitivity analysis showed stable results, with OR estimates ranging from 3.87 to 6.53. A sub-group analysis revealed positive associations between EBV infection and OSCC risk in all sub-groups; however, not all had statistical significance. (November 2017.)

Although there is evidence that a visual examination as part of a population-based screening programme reduces the mortality rate of oral cancer in high-risk individuals, there is otherwise little evidence to support any screening programme for early detection of oral cavity cancers[7].

Medical and dental professionals should remain vigilant for signs of potentially malignant disorders and oral cancer when performing oral examinations[8].

A systematic population screening programme is not currently recommended in the UK[9].

Tongue cancer

  • Malignancies of the tongue may grow to significant size before they cause symptoms.
  • Approximately 75% occur in the mobile tongue:
    • They are often well differentiated. The cancer may spread easily and become symptomatic only when its size interferes with movement:
    • SCC of the tongue may arise in apparently normal epithelium, in areas of leukoplakia, or in an area of chronic glossitis. These lesions are usually larger than 2 cm at presentation, with the lateral border being the most common site.
    • The macroscopic appearance of these lesions depends on the duration of the lesion, the amount of keratinisation and the changes in the adjoining mucosa. A fully developed lesion has the appearance of an exophytic bulky lesion that is grey to greyish-red and has a rough, shaggy or papillomatous surface.
    • The patient may develop speech and swallowing dysfunction.
    • Pain occurs when the tumour involves the lingual nerve and this pain may also be referred to the ear.
  • Carcinomas of the tongue base:
    • These are clinically silent until they deeply infiltrate the tongue musculature. They are usually less differentiated.
    • Because of the difficulties with direct visualisation, they may extend into the oral tongue or have clinical lymph metastases before the diagnosis is established.

Tonsillar cancer

More than 70% of tonsillar cancers are SCC. Most of the others are lymphomas. Metastases to the palatine tonsils are rare but there have been reports of secondaries from breast, lung, renal, pancreatic and colorectal malignancies.

  • Patients with tonsillar carcinomas may present with a neck mass, usually in the jugulodigastric region. Even if the neck mass is not evident on casual inspection, careful palpation may reveal cervical lymphadenopathy.
  • Sore throat, ear pain, foreign body or mass sensation, and bleeding may occur.
  • Trismus is an ominous sign because it probably indicates involvement of the parapharyngeal space. Such tumours may be large enough to involve or encase the carotid sheath. In addition, the tumour may extend to the skull or mediastinum.
  • If the tumour has involved the tongue base, contralateral nodes may be involved.
  • Primary tonsillar tumours may grow entirely beneath the surface. The clinician may therefore see nothing suspicious or may see only a slight increase in the size of the tonsil or the firmness of the area.
  • Alternatively, an exophytic fungating mass with central ulceration and heaped-up edges may be present. It may be deep red to white.
  • Weight loss and fatigue are not uncommon.
  • Treatment may lead to pain, xerostomia, infections, poor wound healing, dysphagia, fistula formation, trismus, potential disfigurement and fatigue.

Buccal mucosa cancer

  • The tumour is usually at the level of the occlusal plane or below it.
  • The lesion is usually painless in the early stages and, only when it becomes ulcerated and secondarily infected or invades an adjacent nerve, is pain the noticeable feature.
  • This may be followed by bleeding and difficulty chewing.
  • They may be proliferative warty exophytic growth with little fixation, or deeply ulcerative invasive lesion.
  • The proliferative lesion, although it looks dangerous, is easily treatable and long-term prognosis is good, as the metastasis to the local lymph nodes is relatively late.
  • In contrast, the ulcerative lesion (which is not so easily noticeable in the early stages) is more dangerous because of its invasive nature and very early metastasis to the local lymph nodes.

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.

  • 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 - through cortical bone, deep/extrinsic muscle of tongue, maxillary sinus, skin.
  • T4b - masticator space, pterygoid plates, skull base, internal carotid artery.

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

Oral metastatic lesions from other sites are uncommon but the most common primary sites are lung, prostate, gastrointestinal tract, thyroid gland, breast and liver[10].

For urgent referrals to assess the possibility of oral cancer, the National Institute for Health and Care Excellence (NICE) recommends[11]:

  • 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.
  • Consider an urgent referral (for an appointment within two weeks) for assessment for possible oral cancer by a dentist in people who have either:
    • A lump on the lip or in the oral cavity; or
    • A red or red and white patch in the oral cavity consistent with erythroplakia or erythroleukoplakia.
  • Altered fractionation radiotherapy is associated with an improvement in overall survival and locoregional control in patients with oral cavity and oropharyngeal cancers[12].
  • Chemotherapy, in addition to radiotherapy and surgery, is associated with improved overall survival in patients with oral cavity and oropharyngeal cancers[13].
  • A Cochrane review found[14]:
    • 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.
    • Insufficient evidence to conclude that elective neck dissection increases overall survival or disease-free survival compared to therapeutic neck dissection.
    • No evidence that radical neck dissection increases overall survival compared to conservative neck dissection surgery.

Early oral cavity cancer

  • Surgical resection, or brachytherapy in accessible well-demarcated lesions. Re-resection should be performed to achieve clear histological margins if the initial resection has positive surgical margins.
  • Clinically, N0 neck disease (levels I-III) should be treated prophylactically either by external beam radiotherapy or selective neck dissection (NB: the neck lymph node levels I-VI are defined in the separate article Head and Neck Cancers).
  • Postoperative radiotherapy should be considered for patients who have positive nodes after pathological assessment.
  • Concurrent administration of cisplatin chemotherapy with postoperative radiotherapy should be considered, especially in patients with extracapsular spread and/or positive surgical margins.

Advanced oral cavity cancer

  • Patients with resectable disease who are fit for surgery should have surgical resection with reconstruction.
  • Patients with node-positive disease should be treated by modified radical neck dissection.
  • Elective dissection of the contralateral neck should be considered if the primary tumour is locally advanced, arises from the midline or if there are multiple ipsilateral nodes involved.
  • Radical external beam radiotherapy with concurrent cisplatin chemotherapy should be considered when:
    • The tumour cannot be adequately resected.
    • The patient's general condition precludes surgery, or
    • The patient does not wish to undergo surgical resection.
  • Bilateral neck irradiation may be required (eg, if the primary tumour is locally advanced, it arises from the midline or there are multiple ipsilateral nodes involved).
  • 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 medically unsuitable for chemotherapy, concurrent administration of cetuximab with radiotherapy should be considered.
  • Postoperative radiotherapy should be considered for patients with clinical and pathological features that indicate a high risk of recurrence.
  • Administration of cisplatin chemotherapy concurrently with postoperative radiotherapy should be considered, especially in patients with extracapsular spread and/or positive surgical margins.

Around 2,100 people died of oral cancer in 2012 in the UK. Two thirds of oral cancer deaths in the UK in 2012 were in men. 74% of oral cancer deaths in the UK in 2012 were in people aged 60 and older. Oral cancer mortality rates have increased by around 10% in the UK in the period of a decade[4].

Tongue cancer

For T1 and T2 lesions, radiotherapy (using interstitial implants with or without external beam radiotherapy) and surgical excision have equivalent results:

  • The five-year disease-free survival rate ranges from 80-90% for lesions treated with either modality (the long-term complications of radiation implants, including local necrosis and bone exposure, are more frequent than those associated with surgery).
  • The five-year survival rates for patients in stages III and IV are 30-50%, decreasing to 15-30% in patients with lymph node metastasis.

Tonsillar cancer

  • The five-year survival rate of treated SCC of the tonsillar region is 80% for stage I but 30% for stage IV.
  • Patients with HPV-positive tumours have improved survival.

Cancer of the buccal mucosa

  • The overall reported five-year survival rates for buccal carcinoma are between 49% and 68%.
  • About 90% of recurrences occur within the first 1.5 years after treatment. Local recurrence (reported rate 23%) is more common than regional recurrence (reported rate of 11%). Distant metastases are uncommon in buccal carcinoma.
  • Lifestyle factors, including smoking avoidance/cessation, avoiding excessive alcohol intake, good dental hygiene.
  • Eating a well-balanced diet can reduce the risk of oral cancer. This includes a diet high in fruits, vegetables and fish and low in high-fat and cholesterol meats, rice and refined grains[15].

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Further reading and references

  1. 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.

  2. Oral cancer statistics; Cancer Research UK

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

  4. Testicular cancer; survival statistics. Cancer Research UK

  5. Andrews E, Seaman WT, Webster-Cyriaque J; Oropharyngeal carcinoma in non-smokers and non-drinkers: a role for HPV. Oral Oncol. 2009 Jun45(6):486-91. Epub 2008 Nov 21.

  6. She Y, Nong X, Zhang M, et al; Epstein-Barr virus infection and oral squamous cell carcinoma risk: A meta-analysis. PLoS One. 2017 Oct 2412(10):e0186860. doi: 10.1371/journal.pone.0186860. eCollection 2017.

  7. Brocklehurst P, Kujan O, O'Malley LA, et al; Screening programmes for the early detection and prevention of oral cancer. Cochrane Database Syst Rev. 2013 Nov 1911:CD004150. doi: 10.1002/14651858.CD004150.pub4.

  8. Walsh T, Liu JL, Brocklehurst P, et al; Clinical assessment to screen for the detection of oral cavity cancer and potentially malignant disorders in apparently healthy adults. Cochrane Database Syst Rev. 2013 Nov 2111:CD010173. doi: 10.1002/14651858.CD010173.pub2.

  9. UK NSC recommendation on Oral Cancer screening in adults; Legacy Screening Portal

  10. Murillo J, Bagan JV, Hens E, et al; Tumors metastasizing to the oral cavity: a study of 16 cases. J Oral Maxillofac Surg. 2013 Sep71(9):1545-51. doi: 10.1016/j.joms.2013.03.017. Epub 2013 Jun 22.

  11. Suspected cancer: recognition and referral; NICE guideline (2015 - last updated December 2021)

  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. 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.

  15. Mangalath U, Aslam SA, Abdul Khadar AH, et al; Recent trends in prevention of oral cancer. J Int Soc Prev Community Dent. 2014 Dec4(Suppl 3):S131-8. doi: 10.4103/2231-0762.149018.