Oral Cavity Carcinoma

Anatomy & Pathophysiology:

The oral cavity consists of the lips, anterior two-thirds of the tongue, floor of mouth (FOM), buccal mucosa, dentoalveolar ridges, retromolar trigone (RMT), and hard palate. Numerous conditions affect the soft tissue, teeth, and bone of the oral cavity. The mucosa may be affected by inflammatory changes, premalignant lesions, and malignancy. Similarly, dentoalveolar structures may harbor development cysts, inflammation, and malignancies. A differential diagnosis is presented in a subsequent section of this chapter. As a thorough discussion of all pathologies is beyond the scope of this text, this chapter will focus primarily on oral cavity carcinoma, which accounts for 14% of all head and neck malignancies.

As with most other regions of the head and neck, squamous cell carcinoma (SCC) represents 90% of malignancies of the oral cavity. Importantly, the accessibility of the oral cavity mucosa allows for ready inspection, such that earlier detection of malignancy should be possible. Oral cavity SCC is most strongly associated with tobacco and alcohol, likely accounting for the 60% male preponderance and the mean age at diagnosis (60-65 years).

The following is a brief summary of anatomic, epidemiologic, and pathophysiologic features of each of the oral cavity subsites pertinent to malignancy:

Lips: The lower lip is a common site for oral cavity cancer. SCC is the most common malignancy of the lower lip; basal cell carcinoma is also common in the upper lip. Sun exposure, tobacco, and alcohol appear to be epidemiological factors. A persistent abnormality of the lower lip should be evaluated, as early tumors may present with an indolent course. Lymphatic spread is uncommon in small lower lip tumors.

Oral tongue: The oral tongue is the other common site of oral cavity malignancy. Tumors of the oral tongue most frequently arise on the lateral surfaces and may be preceded by dysplasia that appears clinically as erythroplakia. Oral tongue tumors may extend to the floor of mouth. Lymphatic drainage of the tongue (to ipsilateral levels I and II nodes) is very common when the tumor thickness is greater than 3-4 mm.

Dentoalveolar ridges: Tumors of the alveolar ridges or gingiva account for up to 10% of oral cavity cancer. It is important to evaluate whether there has been extension through cortical bone to the marrow space, which often occurs along the teeth.

Retromolar trigone: The retromolar trigone refers to the region of gingival tissue that overlies the ascending ramus of the mandible, posterior to the third molar. The RMT is contiguous laterally with the buccal mucosa, and medially with the anterior tonsillar pillar. As with alveolar ridge malignancies, assessing the underlying bone is critical in planning intervention.

Buccal mucosa: The buccal mucosa is a relatively rare site for tumor occurrence in the United States. The incidence of buccal mucosal cancers is much higher in geographic regions where carcinogenic exposure is prevalent, such as in regions of India where betel nut chewing is popular. As elsewhere, SCC of the buccal mucosa frequently arises from dysplastic precursor lesions.

Floor of mouth: The FOM refers to the mucosal surface overlying the mylohyoid and hyoglossus muscles. It extends from the lingual aspect of the mandibular alveolus to the ventral surface of the tongue, and contains the lingual frenulum and submandibular duct openings. Tumors in this region may affect lingual nerves or sublingual glands. Because of the midline location of the FOM, bilateral cervical nodal spread of disease is common.

Hard palate: The hard palate extends from the lingual surface of the maxillary alveolus to the posterior edge of the palatine bone. This subsite is notable for a higher incidence of malignancies other than SCC (50% of tumors), such as tumors of minor salivary gland origin. Surgical resection of tumors in this region is often well-rehabilitated with a prosthesis, with good functional outcomes for swallowing and speech.

Presentation:

Signs and symptoms of oral cavity cancer depend on the subsite of tumor origin. Patients commonly present with pain and bleeding, crusting, or ulcerated mucosal lesions. A patient may be unaware of the presence of early tumor, noted only by a dental professional during an oral examination. Extension of tumor to surrounding structures can cause lead to lip or chin paresthesia, speech impairment, loose teeth, or a neck mass.

Differential Diagnosis of Oral Cavity Tumor:

Evaluation:

History

The patient history should include details of tobacco and alcohol use as well as oral hygiene habits.

Physical Examination

The head and neck examination includes bimanual palpation of all oral cavity subsites. Important tumor features to note include size, location, fixation to underlying or overlying structures, and whether the tumor crosses the midline. Any sensory deficits over the lips, cheeks, and chin should be noted. Tongue protrusion and lateral mobility should be tested. The state of the dentition should be documented, including any missing or loose teeth or dental caries. Dentures, if present, must be removed to enable thorough examination. The neck should be palpated for cervical lymphadenopathy. Flexible fiberoptic laryngoscopy should be done to screen for synchronous lesions and to evaluate for posterior extension into the oropharynx.

Biopsy

A tissue biopsy is necessary to confirm a diagnosis of oral cavity carcinoma. In many cases, this can be done in an office with local anesthesia; alternatively, a fine needle aspiration biopsy of a palpable node can be taken.

Imaging Studies

Radiographic evaluation of oral cavity carcinoma is best done with magnetic resonance imaging (MRI), as the soft tissue definition is superior to computed tomography (CT). MRI also allows for better evaluation of both the mandibular marrow space and superior extension to the sinuses. Occasionally, CT is complementary, but the technique is often affected by dental artifact. Positron emission tomography (PET)-CT scanning is often ordered to assess for nodal and distant metastases.

Staging

Staging of oral cavity cancer is according to the American Joint Committee on Cancer (AJCC) TNM (tumor, node, metastasis) system.

AJCC TNM Staging for Lip and Oral Cavity
Primary Tumor (T)
T1	Tumor <2 cm in greatest dimension
T2	Tumor >2 cm and <4 cm in greatest dimension
T3	Tumor >4 cm in greatest dimension
T4 (lip)	Primary tumor invading cortical bone, inferior alveolar nerve, floor of mouth, or skin of face
T4a (OC)	Tumor invades adjacent structures (e.g., through cortical bone, into deep tongue musculature, maxillary sinus) or skin of face
T4b (OC)	Tumor invades masticator space, pterygoid plates, or skull base, or encases the internal carotid artery
Nodal Metastasis (N)
NX	Regional lymph nodes cannot be assessed
N0	No regional lymph node metastasis
N1	Metastasis in a single ipsilateral lymph node, ≤3 cm in greatest dimension
N2a	Metastasis in a single ipsilateral lymph node, >3 cm but <6 cm in greatest dimension
N2b	Metastasis in multiple ipsilateral lymph nodes, none >6 cm in greatest dimension
N2c	Metastasis in bilateral or contralateral lymph nodes, none >6 cm in greatest dimension
N3	Metastasis in a lymph node, >6 cm in greatest dimension
Distant Metastasis (M)
MX	Distant metastasis cannot be assessed
M0	No distant metastasis
M1	Distant metastasis present
Staging Groups
Stage	T	N	M
I	T1	N0	M0
II	T2	N0	M0
III	T3	N0	M0
	T1-3	N1	M0
IVA	T4a	N0-1	M0
	T1-4a	N2	M0
IVB	T4b	Any N	M0
	Any T	N3	M0
IVC	Any T	Any N	M1

Treatment:

The mainstay of treatment for oral cavity carcinoma is surgical resection. In early stage disease, surgery may be used as the only modality of therapy. In advanced disease, surgery is generally followed by adjunctive radiotherapy, with or without chemotherapy.

Lip

Resection of lip tumors is primarily challenging from a reconstructive perspective. Reconstructive options depend on the amount of lip resected. Defects less than one-third of the length of the lip can usually be closed primarily. Local flaps of varying types are used for larger defects and microvascular free flaps may be used to repair the largest defects.

Oral tongue

Tongue tumors can generally be resected transorally, with the amount of resection dependent on the size of the tumor. Frozen section pathologic analysis of surgical margins at the primary site is typically done to confirm adequate resection prior to reconstruction. Reconstructive options and potential for functional restoration depend on the size of the surgical defect. Smaller tongue defects (less than one-third of the oral tongue) can be left to heal by secondary intention or closed primarily. Some surgeons consider skin grafting for a floor of mouth tumor, hoping to prevent contracture and fixation of the tongue. Resection of significantly more than half of the tongue may result in impaired handling of food and compromised swallowing or pronunciation, whether a flap reconstruction is done or not. A microvascular free flap is commonly utilized for large soft tissue reconstructions, particularly if mandibulectomy is also done (composite resection).

Dentoalveolar ridge

The extent of resection in alveolar ridge tumors depends on whether bony invasion has occurred. Periosteal involvement requires a marginal mandibulectomy, wherein the superior cortex is removed, leaving the continuity of the inferior mandible intact. Invasion of tumor into the medullary bone requires segmental mandibulectomy, which entails en bloc removal of an entire segment of mandibular bone. Reconstruction after segmental mandibulectomy is best done via an osteomyocutaneous microvascular fibular free flap; however, for lateral defects in patients with significant comorbidities, a pectoralis major myocutaneous flap over a titanium bar is associated with less perioperative risk.

Retromolar trigone

Retromolar trigone cancer tends to present at a later stage than other oral cavity malignancies. Mandibulectomy is often indicated due to bony involvement.

Buccal mucosa

Buccal mucosal cancers are generally resected transorally. In most cases, the depth of excision should extend to include at least the buccinator muscle. Deep extension may require a through-and-through resection that includes cheek skin, with local or free flap reconstruction.

Floor of mouth

Floor of mouth carcinoma may be resected transorally if no mandibular involvement is present. If deep soft tissue extension is present, a supplemental transcervical approach is often warranted. Composite resection is indicated if bony invasion is present. Microvascular free flap reconstruction is useful to reconstruct the mandible after a composite resection. Cervical nodal metastasis is common in FOM carcinoma, with bilateral nodal spread frequently seen in anterior FOM tumors.

Hard palate

Resection of small hard palate malignancies without bony involvement is done transorally. More extensive tumors may require resection of the bony palate and an inferior maxillectomy. A maxillofacial prosthodontist should be consulted preoperatively, as a dental prosthesis often addresses the subsequent oroantral or oronasal defect. The incidence of occult cervical metastasis is low in hard palate SCC; therefore, no treatment is recommended for the clinically negative neck.

Management of the neck

For all of the above sites, a comprehensive neck dissection is recommended when nodal metastases are present. A selective neck dissection (supraomohyoid neck dissection: levels I-III) should be considered when there is no evident nodal metastasis but where the risk is high, such as when a tongue tumor is more than 3-4 mm deep. A third indication for at least a selective neck dissection is when the neck must be entered, either to resect the primary or as part of the reconstruction (such as for vascular access for a free flap).

Postoperative adjuvant radiation

Postoperative irradiation (or chemoradiation) is indicated in cases with positive surgical margins, T3-4 disease, extensive regional lymph node metastasis (most cases of N2b, all cases of N3), presence of extracapsular spread, and perineural invasion at the primary site.

Complications, Prognosis & Follow-Up:

The prognosis for oral cavity malignancy varies according to the site of tumor origin.

Lip

Carcinomas of the lip, like most non-melanoma cutaneous neoplasms, have a very high survival rate (overall 5-year survival of >90%). Poor prognostic indicators include the presence of cervical nodal metastasis and involvement of the oral commissure or upper lip.

Oral tongue

Cancers of the oral tongue have 5-year survival rates of 60-90% for early stage disease, but 25-40% for advanced disease. Nodal disease, especially with extracapsular spread, is a negative prognostic indicator. Recurrent disease does worse than initial disease, likely both because of underlying biological aggressiveness of the tumor and limitations of subsequent intervention if there has been prior irradiation.

Dentoalveolar ridge

Alveolar ridge carcinoma has a 5-year survival of 85% for early stage disease, 65% for advanced disease without distant metastasis, and 35-60% for cases with distant spread. Negative prognostic indicators include advanced T-stage, positive surgical margins, mandibular invasion, and presence of nodal metastasis.

Retromolar trigone

Five-year survival rates for retromolar trigone carcinoma are reported as 76% overall, with lower survival in advanced T- and N-stages. Survival rates for N2 disease may be as low as 25%.

Buccal mucosa

Buccal mucosal carcinoma has a 5-year survival rate ranging from 75% at stage I to 20-50% for stage IV. Locoregional recurrence rates are high.

Floor of mouth

Prognosis for early stage floor of mouth carcinoma is quite good, with 5-year survival rates in the 80-90% range. This decreases significantly with increased disease stage to only 30% for stage IV tumors.

Hard palate

Hard palate malignancies are prone to locoregional recurrence at higher stages. Five-year survival rates range from 44-75% overall. The prognosis is better for salivary gland malignancies than for squamous cell carcinoma.

Follow-up after treatment of oral cavity malignancies addresses multiple issues in addition to surveillance for tumor recurrence. Surgical resection in the region may affect speech and swallowing, causing significant impact on patient quality of life. Postoperative radiotherapy may further exacerbate these problems and is associated with xerostomia and the risk of osteoradionecrosis, should a dental extraction be needed in the future. Preoperative dental assessment, excellent dental hygiene, and lifelong local fluoride rinses help minimize the effect of irradiation on dentoalveolar structures. Rehabilitative speech therapy and nutritional counseling may be of benefit and should be considered.