The oral cavity extends from the lips anteriorly to the circumvallate line and hard–soft palate junction posteriorly. The lips include the apposing vermilion surfaces with upper and lower portions joining laterally at the oral commissures. The buccal mucosa separates the lips from the mandibular and maxillary alveoli which contain 32 teeth in most adults. Multiple minor salivary glands are found here, as well as the orifice of Stenson's duct which is located just opposite the upper second molar tooth. From here the duct courses toward the anterior border of the masseter muscle on its way to the parotid gland. Posterior to the molars the mandible courses cephalad, forming the deep margin of a triangular mucosal region known as the retromolar trigone, which extends from the distal surface of the third molar tooth to the maxillary tuberosity. The hard palate lies posterior to the maxillary teeth and is formed by the maxillary and palatine bones. The mucoperiosteum here is directly apposed to bone, with an abundance of minor salivary glands but few lymphatics. The floor of mouth includes the soft tissue compartment between the mandibular alveolus and the ventral surface of the tongue. The frenulum of the tongue here lies in the midline and is straddled by the papillary openings to Wharton's ducts from the submandibular salivary glands and minor duct orifices from the sublingual salivary glands. Deep to the mucosa course the lingual and hypoglossal nerves, the former in association with Wharton's duct. The tongue lies posterior to the floor of mouth and is divided into ventral, lateral, tip, and dorsal regions. Filiform, foliate, and fungiform papillae occupy the oral tongue and contain varying proportions of taste buds whose receptors transmit taste through the seventh cranial nerve. Intrinsic and extrinsic tongue musculature alters tongue shape during deglutition and speech and is controlled by the paired hypoglossal or twelfth cranial nerves.

The oropharynx begins anteriorly at the circumvallate line at the posterior third of the tongue. The large circumvallate papillae form an inverted V which separates the oral tongue from the tongue base. Here the glossopharyngeal (ninth cranial nerve) supplies touch, pain, and taste sensations. The valleculae are two small fossae that lie posterior to the tongue base, separating it from the epiglottis. Laterally the palatine tonsil, tonsil fossa, anterior and posterior pillars form the lateral oropharynx, limited deeply by the superior and middle pharyngeal constrictor muscle. Superiorly lies the mucosally lined muscular curtain of the soft palate, formed by the palatoglossus, glossopharyngeus, levator veli palatini, tensor veli palatini, and uvular muscles. The posterior oropharynx overlies the vertebral bodies and retropharyngeal space, extending from the level of the tip of the epiglottis to the plane of the hard palate, distinguishing it from the hypopharynx and nasopharynx, respectively.

The mucosa of the oral cavity is made up of a stratified squamous epithelium with varying thicknesses of submucosa. Multiple minor salivary glands, mucus glands, and taste buds are scattered throughout the mucosa. Submucosal lymphatic tissue, including the tubal, palatine, pharyngeal, and lingual tonsils, forms a circular aggregate known as Waldeyer's ring.

The oral cavity and pharynx are supplied by cranial nerves V, VII, IX, X, and XII. The predominant blood supply is from branches of the external carotid artery, especially the lingual and facial arteries. Venous drainage is to the internal jugular vein.

Approximately 19000 new cases of oral cancer and 7000 new cases of oropharyngeal cancer are diagnosed each year. The most important risk factors for development of oral and oropharyngeal cancers include cigarette smoking and use of alcohol, chewing tobacco, and snuff. Cigarette smoke contains carcinogens that act directedly on the mucosa, while alcohol acts both as a direct carcinogen and as a facilitator for the absorption of carcinogens from cigarette smoke. The risk of cancer developing in smokers who drink is therefore higher than that in non-drinking smokers. Pipe smoking and exposure to ultraviolet light is most associated with lip cancers. Alcohol may also act indirectly by its systemic effects on nutrition and immune surveillance. The contribution of poor oral hygiene and trauma (e.g. an ill-fitting denture plate) to the risk of the disease has been noted, but this is difficult to quantitate. Although syphilis has been implicated in the aetiology of oral cancer in the past, more recent studies cast doubt on its role in the disease.

In the East and Far East, where oral cancers make up as many as half of all malignancies, other carcinogens have been noted. Chewing of betel nuts and reverse smoking of chuttas predispose to oral carcinomas in this part of the world. Patients with head and neck cancer often show depressed cellular immunity, although the importance of this in predisposing to malignancy has not been clearly defined. Tongue cancers have been associated with cirrhosis and with the Plummer–Vinson syndrome. Other possible aetiological factors include viruses and industrial chemical agents.

The most common presentation of oral cancer is a painless mass in the mouth. Despite the fact that most oral lesions are readily apparent, patients often present with advanced cancers which have caused pain, ulceration, referred otalgia, bleeding, and cervical masses. The presentation may be delayed by an altered sensorium due to alcohol abuse, patient denial, or prolonged therapy for an incorrect diagnosis of infection. Some patients develop carcinoma in areas of leukoplakia. These white, mucosal lesions usually represent benign hyperkeratosis, but they occasionally harbour squamous cell carcinoma. Red, slightly raised, friable lesions known as erythroplakia harbour carcinoma more often. Monitoring of patients with these lesions through regular examination and appropriate biopsy is useful in detecting early carcinomas.

The most common finding on physical examination is a mass lesion in the mouth. This can be exophytic and friable or ulcerative and apparently infiltrative in cases of squamous cell carcinoma. Adenocarcinomas often begin as submucosal masses, involving the mucosa relatively late in their course. The tumour may be palpably mobile or fixed to underlying soft tissue or bone. A careful, systematic examination of the oral cavity with excellent illumination is critical. Bimanual palpation of the tongue and floor of mouth along with the submandibular and submental areas is often useful in defining the lesion. Occasional benign lesions such as mandibular tori (benign bony projections on the inner aspect of the jaw) or submandibular duct calculi can be easily differentiated from tumour. There may be areas of leukoplakia or erythroplakia surrounding a mucosal lesion, or skip areas suspicious for carcinoma. Such findings are consistent with the concept of ‘field cancerization’, resulting from the simultaneous, chronic exposure of different mucosal areas to carcinogens. This principle also explains the common finding of multiple synchronous or metachronous squamous cell cancers in the head and neck. Large tumours occasionally undergo significant necrosis, leading to a foul odour emanating from the mouth. Involvement of the muscles of mastication can lead to trismus in advanced disease. Hypoglossal nerve involvement results in ipsilateral tongue weakness. Mandibular anaesthesia may be due to bone erosion with involvement of the inferior alveolar nerve.

Cervical palpation may reveal abnormally enlarged, indurated, and/or fixed nodes, most commonly in the submandibular, submental, and upper jugular chains. However, adenopathy may involve the middle and inferior jugular chains, the lateral retropharyngeal nodes, the periparotid nodes, and the posterior cervical triangle. Involvement of the contralateral side of the neck is not uncommon, especially with floor of mouth and tongue lesions. In these areas there is little lymphatic compartmentalization, and drainage pathways cross the midline, allowing bilateral metastatic spread. Ipsilateral cervical metastasis also blocks and reroutes predictable lymphatic flow, occasionally allowing contralateral tumour spread.

Oropharyngeal tumours tend to produce few early symptoms and can become quite large before being detected. Patients usually note soreness in the throat on swallowing and may develop referred otalgia mediated through cranial nerves IX and X. Late involvement of the pterygoid muscles produces trismus. Tumour necrosis may produce bleeding and foul odour. Masses affecting the base of the tongue may give the voice a muffled quality, while tonsillar tumours may involve the inferior alveolar nerve, with resulting mandibular anaesthesia. Cervical metastasis tends to occur more frequently in oropharyngeal cancer than in oral malignancies. The upper jugular nodal chain is most commonly involved, although retropharyngeal and spinal accessory nodes are more frequently involved than in oral carcinomas. The middle and lower jugular nodes become affected in advanced disease. There is a higher rate of contralateral cervical metastatic spread than is seen with oral tumours. This spread is due to the dense lymphatic network which tends to cross the midline with few anatomical barriers. The idea that oropharyngeal tumours are more aggressive than oral tumours may be a misconception due to their often ‘silent’ nature and later presentation.

Examination of the oropharynx, directly and with mirrors, usually reveals an exophytic or ulcerated mass. Occasionally tumours show little mucosal change, especially at the base of tongue. Palpation is important and should be performed bimanually, with simultaneous intraoral and cervical manipulation. The tonsillar fossa and the base of tongue are two of the most common sites for occult squamous cell carcinoma, and these should be examined carefully in patients who present with cervical metastatic disease with an ‘unknown’ primary tumour. Cervical palpation usually reveals a higher incidence of bilateral and posterior triangle disease than is seen in oral tumours.

Carcinoma of the lip occurs most commonly on the lower lip and least frequently at the oral commissures. Early findings of a bleeding, ulcerative lesion may eventually progress to cervical metastasis, mental nerve involvement, and mandibular invasion. Upper lip carcinomas tend to metastasize earlier and grow more rapidly than lower lip lesions. Early (T1) tumours can be managed by local wedge resection, including at least 0.5cm of normal tissue with pathological margins. More advanced lesions usually require combined surgery and radiation therapy. Overall 5-year survival is between 65 and 80 per cent.

Tongue carcinoma is second only to cancer of the lip in frequency. As in other head and neck cancers, this tumour tends to occur in older males who smoke and drink excessively. However, tongue cancer has also been noted in younger individuals with no predisposing history and should therefore not be overlooked in this population. The most common site of disease is along the lateral border of the middle third of the tongue; very few tumours occur on the dorsum. Cervical metastasis at presentation is common. The primary tumour is treated by either surgery or radiation therapy (T1 and T2 lesions); more advanced disease requires combination therapy. Patients with early lesions treated surgically who have no clinical nodal disease require radiation treatment to the neck because of the significant incidence of occult cervical metastasis. Overall 5-year survival is about 50 per cent.

Carcinomas of the floor of mouth usually begin anteriorly and can go on to invade the submandibular ducts, root of the tongue, and mandible. About half of the tumours have metastasized to lymph nodes at presentation, with significant occult nodal involvement in N0 disease. T1 and T2 lesions are treated with surgery or radiation, although radiotherapy to the cervical area for occult disease is important. Combination therapy is necessary for advanced disease. Mandibular involvement should be assessed by palpation and radiologically. Periosteal attachment or superficial invasion requires at least a partial thickness resection of bone, while radiographically confirmed destruction requires segmental mandibular resection. Overall 5-year survival is about 40 per cent.

The alveolar ridge is a relatively infrequent site of carcinoma. Here the aetiology is often related to local trauma from a denture, in addition to smoking and alcohol use. Most tumours are located on the lower gingiva posteriorly. Up to half affect bone, because of the direct apposition of the mucoperiosteum to the mandible. Surgery is the preferred treatment for T1 and T2 lesions, because of the risk of osteoradionecrosis of the mandible with radiation therapy. More advanced disease requires combined therapy with segmental mandibulectomy and the requisite reconstruction. Overall 5-year survival is 50 to 65 per cent.

The buccal area is an uncommon site of carcinoma. In addition to smoking and alcohol use, chewing tobacco and snuff have been implicated as aetiological factors, and local trauma from nearby teeth may also contribute. A small proportion of tumours at this site are verrucous carcinomas, relatively low-grade malignancies with low metastatic potential and a deceptively benign papillary appearance histologically. Deep extension or infiltration of other oral cavity sites is common, especially with the infiltrative variety of squamous carcinoma. Early lesions require surgery or radiation therapy. Verrucous carcinoma is usually managed surgically; there is some evidence of its anaplastic transformation with radiation therapy. Combination therapy for larger lesions is probably prudent, although surgery alone has been used successfully. Overall 5-year survival is about 50 per cent.

Hard palate cancers are about equally divided into squamous cell carcinomas and salivary gland malignancies. Squamous cell carcinoma of this site is rare, except in parts of the East where reverse smoking is practised. The tumour tends to spread tangentially as it grows since the periosteum acts as a barrier to bone destruction early in the disease process. Cervical metastasis is not common, due in part to the relatively sparse lymphatics. Although radiation therapy has been used for small lesions, surgery is the mainstay of treatment. Overall 5-year survival is about 60 per cent.

Cancer of the retromolar trigone tends to be less well differentiated than tumours located more anteriorly in the oral cavity. Mandibular invasion is common because of the direct apposition of the mucoperiosteum at this site. Superficial lesions should be treated with radiation therapy to avoid the effects of surgery on speech and swallowing. However, when bone is invaded surgery combined with radiation therapy is indicated. Five-year survival is difficult to assess here because this area is often included with nearby sites in reporting results.

The tonsillar fossa is the most common site of oropharyngeal malignancy. Many malignancies of this site are lymphoma, but the majority are squamous carcinomas. Extension to the base of tongue, soft palate, retromolar trigone, and pterygoid muscles is not uncommon. Occasionally a mass high in the cervical area is evidence not of metastasis, but of direct extension into the parapharyngeal space. T1 and T2 lesions are managed with radiation therapy, including the ipsilateral neck. More advanced lesions and T2 tumours that fail to regress adequately during radiation therapy should be treated with combined therapy. Five-year survival is as high as 93 per cent for patients with T1 lesions but drops to 27 per cent and 17 per cent for stage III and IV disease, respectively.

Soft palate cancers tend to be diffuse tumours and may be mixed in with premalignant ‘field’ changes as well as nicotine stomatitis. There is a propensity for bilateral metastasis to the neck and thus prophylactic irradiation of both cervical areas is necessary. Early lesions are best treated with radiotherapy to avoid the effects of surgery on speech and deglutition. More advanced disease is best managed with combination therapy. Cure rates of 70 to 90 per cent for T1 and T2 lesions drop to 20 to 30 per cent for more advanced disease.

Cancers of the base of the tongue tend to present late; most are advanced at the primary site, often associated with bilateral cervical metastases. Most of these tumours require combined therapy, but the prognosis remains poor in general. Five-year cure rates are usually about 30 per cent.

The most important aspect of diagnosis of an oral or oropharyngeal mass lesion is a careful examination and biopsy. This can often be performed under local anaesthesia. Biopsy usually consists of a punch or wedge of tissue taken from the periphery of the mass, both to allow comparison with the surrounding normal tissue and to avoid sampling only necrotic tissue at the centre of the mass. The specimen should be submitted for pathological examination in an appropriate fixative such as formalin. Because of the concept of ‘field cancerization’ an examination under general anaesthesia allows the addition of endoscopy and tumour mapping. Endoscopy usually consists of direct laryngoscopy, rigid oesophagoscopy, and bronchoscopy in order to detect second primary malignancies of the head and neck. Tumour mapping involves outlining the tumour mass by tattooing the surrounding normal mucosa with India ink. This method offers the surgeon a fairly permanent marking of the tumour for purposes of determining original extent following treatment with chemotherapy or radiation therapy.

Biopsy specimens of any cervical adenopathy should be limited to fine needle aspiration for cytology. Large bore needle biopsy and open surgical biopsy have been associated with a reduction in survival, presumably due to tumour dissemination. Abnormal adenopathy in the presence of an oral carcinoma should be presumed to represent metastasis, so that cervical tissue diagnosis is rarely necessary. In patients with cervical adenopathy and a primary tumour of unknown site, open biopsy should be preceded by endoscopy with random biopsies of suspicious occult sites (base of tongue, tonsillar fossa, nasopharynx, and piriform sinus). Immediate neck dissection should be performed following confirmation of malignancy.

The local and regional extent of tumour can be further clarified by appropriate imaging studies, although these examinations are ancillary and should not be necessary for diagnosis. Orthoplanograms (panorex) are useful to assess mandibular bony invasion by tumours originating close to the mandible. These are also useful in differentiating between primary bony tumours and cysts. Barium swallow is especially useful in evaluating the inferior extent of oropharyngeal tumours. CT scanning can define bony invasion, extension into the nose or maxillary sinuses, prevertebral invasion, pterygoid and parapharyngeal space disease, and the extent of cervical metastasis. Magnetic resonance imaging (MRI) may offer superior resolution of soft tissue detail in comparison to CT, but is limited in evaluating bony involvement. CT and MRI may be useful in determining the resectability of advanced tumours in certain instances and may allow assessment of response to therapy in certain deeply invasive malignancies. Bone scanning, gallium scanning, and sialography are rarely useful in assessing oral cancers.

The clinical staging of oral and oropharyngeal tumours is listed in Table 1 608. In general, larger oral tumours are associated with an increased risk of cervical metastasis, although this does not always hold true. The staging system according to the American Joint Committee (AJC) is useful for purposes of prognostication, treatment planning, and reporting. In general, stage I and II disease is treatable with either surgery or radiation. Advanced disease in stages III and IV requires combined therapy with both surgery and radiation for maximum rates of cure. Cure here is defined as no evidence of disease 5 years following treatment.

Ninety per cent of oral cavity malignancies are squamous cell carcinomas. Histologically, squamous carcinomas at this site usually exhibit relatively less pleomorphism, few mitoses, and significant keratinization (grades I and II) compared to the less frequent, more poorly differentiated cancers (grades III and IV). Adenocarcinomas of salivary gland origin make up the bulk of the remaining malignancies. Other more unusual cancers include sarcomas, melanomas, lymphomas, and metastatic disease. More recently oral Kaposi's sarcoma has been noted with increased frequency in patients with AIDS.

Squamous cell carcinomas are most commonly ulcerative, with relatively early metastasis and higher histological grade. The infiltrative form shows less surface change but is similarly aggressive. Exophytic tumours are less common and tend to grow along mucosal surfaces and metastasize later in their course. The least common form is verrucous carcinoma, a relatively benign appearing, papillary lesion found most commonly along the buccal mucosa. This proliferative, well-differentiated lesion may be mistaken for benign hyperplasia, leading to underdiagnosis. Although it carries the best prognosis of the various types of squamous cell carcinoma it can be locally aggressive. Its diagnosis requires a high index of suspicion.

Unusual malignancies include lymphomas, melanomas, sarcomas, and metastatic disease from distant sites.

‘Field cancerization’ refers to the risk of synchronous or metachronous second malignancies related to the chronic, simultaneous exposure of multiple areas of the upper aerodigestive tract to carcinogenic influences. In a Mayo Clinic series, second primary cancers of the oral cavity, pharynx, or oesophagus were noted in 16.3 per cent of 732 patients with squamous cell carcinoma of the oral cavity. Thus, the rule of initial ‘panendoscopy’ (direct laryngoscopy, oesophagoscopy, bronchoscopy, and nasopharyngoscopy) to search for synchronous second primary tumours as well as careful follow-up monitoring for metachronous second malignancies, is critical.

In the oropharynx squamous cell carcinoma is often non-keratinizing and poorly differentiated, although the histology of the tumour at a specific site appears to make little difference prognostically. In addition there are more unusual variants of squamous cell carcinoma including spindle cell and adenoid squamous cell carcinoma which are treated in the same fashion. Verrucous carcinoma is these sites is rare. Lymphomas, especially in the tonsillar and base of tongue areas are more common than in the oral cavity.

Over 80 per cent of tumours in minor salivary glands of the oral cavity are malignant. These tumours consist of adenoid cystic carcinomas, adenocarcinomas, and mucoepidermoid carcinomas. They occur mostly on the posterior hard palate and tend to present as painless, non-ulcerated submucosal masses. Wide resection with or without radiation therapy produces a 5-year survival rate of about 40 per cent. This figure can be deceiving, however, in light of the significant incidence of recurrence at 10 and 15 years. Salivary malignancies rarely also involve the oropharynx.

A detailed discussion of radiation therapy for oral and oropharyngeal malignancy is beyond the scope of this chapter. In general oral squamous cell carcinomas are treated with 65 to 60Gy of external beam radiotherapy. The cervical areas at risk are included in the treatment field in N0 disease when the risk of occult metastasis is significant (>25per cent). In combination therapy 55 to 60Gy are administered to the primary site and neck following surgical resection. Intraoral cone irradiation along with radium or iridium-192 implants can be used in combination with external beam therapy. This programme offers the advantage of a relatively high dose of radiation to a small treatment volume. The complications of treatment include xerostomia, mucositis, loss of taste, and the infrequent although dreaded osteoradionecrosis of the mandible.

Surgical therapy of oral and oropharyngeal carcinomas requires radical or modified neck dissection for the treatment of clinically apparent or proved metastatic lymphadenopathy. This en-bloc resection of cervical nodes includes removal of the sternocleidomastoid muscle, internal jugular vein, and the spinal accessory (XI) nerve. Primary site resection can sometimes be performed transorally for earlier lesions and involves excision with a gross margin of 2cm of normal tissue. Primary closure is often possible; reconstruction using a dermal or free mucosal graft may be needed where mucosa cannot be advanced or rotated, or where tethering of the mobile tongue may result. Lip lesions can often be removed by wedge resection with either primary closure or use of nasolabial flaps for reconstruction. More advanced lesions intraorally and in the oropharynx require median mandibulotomy for access to the tumour for resection and reconstruction (Figs. 1 and 2) 2346,2347. Exposure can be performed through a lower lip splitting approach with elevation of a cheek flap or through a submandibular degloving approach to the mandible. Resection may require segmental mandibulectomy, creating not only a soft tissue, but also a bony defect. Rehabilitation of speech and deglutition requires reconstruction of the resultant defect, using local and regional tongue, cutaneous, and myocutaneous flaps (Fig. 3) 2348. Mandibular reconstruction using stainless steel plating, pedicled and microvascular osteomyocutaneous flaps, and bone trays can be performed.

Recurrent disease can additionally be treated with laser vaporization or cryotherapy for palliation.

While combination therapy with surgery and radiation has improved local control, it has done little to improve overall survival in patients with oral and oropharyngeal cancer. In an effort to improve long-term results, various combinations of induction and adjuvant chemotherapy have been investigated recently. One such study at the Dana-Farber Cancer Institute has used cisplatin, 5-fluorouracil, and leucovorin as an induction protocol for treating stage III and IV squamous cell carcinoma of the head and neck. Clinical responses were recorded in 78 per cent of 46 patients treated with this regimen, with 65 per cent complete responses. Eighty per cent of the patients were disease free after surgery or radiation, although long-term survival figures are not yet available. Primary site management with radiation alone was possible in 78 per cent of patients, obviating the need for local radical resection. Systemic treatment of this type may produce less functional and cosmetic debility in treating these advanced tumours and perhaps prevent the later occurrence of distant metastases seen in patients with adequate local control of disease.

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