Cancer of the oral cavity is one of the most common malignancies worldwide. Although early diagnosis is relatively easy, presentation with advanced disease is not uncommon. The standard of care is primary surgical resection with or without postoperative adjuvant therapy. Improvements in surgical techniques combined with the routine use of postoperative radiation or chemoradiation therapy have resulted in improved survival. Successful treatment is predicated on multidisciplinary treatment strategies to maximize oncologic control and minimize impact of therapy on form and function. Prevention of oral cancer requires better education about lifestyle-related risk factors, and improved awareness and tools for early diagnosis.
Key points
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Cancer of the oral cavity is a common malignancy in the United States and around the world.
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The standard of care is primary surgical resection with or without postoperative adjuvant therapy.
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Multidisciplinary treatment is crucial to improve the oncologic and functional results in patients with oral cancer.
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Primary and secondary prevention of oral cancer requires education about lifestyle-related risk factors, and improved awareness and tools for early diagnosis.
Introduction
Cancer of the oral cavity is one of the most common malignancies, especially in developing countries but also in the developed world. Squamous cell carcinoma (SCC) is the most common histology, and the main etiologic factors are tobacco and alcohol use. Although early diagnosis is relatively easy, presentation with advanced disease is not uncommon. The standard of care is primary surgical resection with or without postoperative adjuvant therapy. Improvements in surgical techniques combined with the routine use of postoperative radiation or chemoradiation therapy have resulted in improved survival statistics over the past decade. Successful treatment of patients with oral cancer is predicated on multidisciplinary treatment strategies to maximize oncologic control and minimize impact of therapy on form and function.
Introduction
Cancer of the oral cavity is one of the most common malignancies, especially in developing countries but also in the developed world. Squamous cell carcinoma (SCC) is the most common histology, and the main etiologic factors are tobacco and alcohol use. Although early diagnosis is relatively easy, presentation with advanced disease is not uncommon. The standard of care is primary surgical resection with or without postoperative adjuvant therapy. Improvements in surgical techniques combined with the routine use of postoperative radiation or chemoradiation therapy have resulted in improved survival statistics over the past decade. Successful treatment of patients with oral cancer is predicated on multidisciplinary treatment strategies to maximize oncologic control and minimize impact of therapy on form and function.
Anatomy of the oral cavity
The oral cavity extends from the vermilion border of the lips to the circumvallate papillae of the tongue inferiorly and the junction of the hard and soft palate superiorly. The oral cavity is divided into several anatomic subsites: lip, oral tongue, floor of the mouth, buccal mucosa, upper and lower gum, retromolar trigone, and hard palate ( Fig. 1 ). Despite their proximity, these subsites have distinct anatomic characteristics that need to be taken into account in planning oncologic therapy.
Epidemiology and etiology
Worldwide, 405,000 new cases of oral cancer are anticipated each year, the countries with the highest rates being Sri Lanka, India, Pakistan, Bangladesh, Hungary, and France ( Fig. 2 ). In the European Union there are an estimated 66,650 new cases each year. The American Cancer Society estimates that there will be 45,780 new cancers of the oral cavity and pharynx in the United States in 2015, causing 8,650 deaths.
Tobacco smoking and alcohol are the main etiologic factors in SCC of the oral cavity (SCCOC). Other habits such as chewing of betel nuts and tobacco have been implicated in the Asian population. Tobacco contains many carcinogenic molecules, especially polycyclic hydrocarbons and nitrosamines. A directly proportional effect exists between the pack-years of tobacco used and the risk of SCCOC. This risk can be reduced after tobacco cessation, but does not fully abate (30% in the first 9 years and 50% for more than 9 years). A decreased incidence of oral cavity cancer has been reported in the last 15 years, widely attributed to a reduction in tobacco use.
Alcohol and tobacco seem to have a synergistic effect in the etiology of oral and oropharyngeal SCC. However, alcohol is linked to an increased risk of cancer even in nonsmokers. Other factors such as poor oral hygiene, wood dust exposure, dietary deficiencies, and consumption of red meat and salted meat have been reported as etiologic factors. The herpes simplex virus (HSV) has been suspected but has not been implicated in the etiology of SCCOC. Despite the emerging evidence supporting the role of the human papillomavirus (HPV) in the etiology of oropharyngeal cancer, it has not been conclusively linked to SCCOC. Host factors such as immune-system alterations in transplant patients and human immunodeficiency virus–infected patients with AIDS, and genetic conditions such as xeroderma pigmentosum, Fanconi anemia, and ataxia-telangiectasia are associated with an increased incidence of head and neck cancer.
Oral cancer is more common in men and usually occurs after the fifth decade of life. Approximately 1.5% will have another synchronous primary in the oral cavity or the aerodigestive tract (larynx, esophagus, or lung). Metachronous tumors develop in 10% to 40% in the first decade after treatment of the index primary ; therefore, regular post-therapy surveillance and lifestyle alteration are important strategies for secondary prevention.
Pathology
SCCs constitute more than 90% of all oral cancers. Other malignant tumors can arise from the epithelium, connective tissue, minor salivary glands, lymphoid tissue, and melanocytes, or metastasis from a distant tumor.
A variety of premalignant lesions have been associated with development of SCC. The more common premalignant lesions including leukoplakia, erythroplakia, oral lichen planus, and oral submucous fibrosis have varying potential for malignant transformation. The 2005 classification of the World Health Organization categorizes premalignant lesions according to degree of dysplasia into mild, moderate, severe, and carcinoma in situ.
Leukoplakia is a clinical term defined as a “white patch or plaque that cannot be characterized clinically or pathologically as any other disease.” This lesion is usually associated with smoking and alcohol use. The prevalence of leukoplakia worldwide is about 2%. Dysplastic changes are seen in only 2% to 5% of patients. The annual rate of malignant transformation for leukoplakia is 1%. Risk factors for malignant transformation include presence of dysplasia, female gender, long duration of leukoplakia, location on the tongue or floor of the mouth, leukoplakia in nonsmokers, size greater than 2 cm, and nonhomogeneous type. In addition to lifestyle alteration to avoid tobacco and alcohol use, excision constitutes the only definitive modality for accurate diagnosis and treatment.
Erythroplakia is a “bright red velvety patch that cannot be characterized clinically or pathologically as being caused by any other condition.” Surgical excision is recommended, as these lesions have higher malignant potential than leukoplakia and are commonly associated with dysplasia and carcinoma in situ.
Nonsquamous cell carcinomas of the oral cavity are uncommon. Minor salivary gland carcinomas, representing less than 5% of the oral cavity cancers, frequently arise on the hard palate (60%), lips (25%), and buccal mucosa (15%). Mucoepidermoid carcinoma is the most common type (54%), followed by low-grade adenocarcinoma (17%) and adenoid cystic carcinoma (15%).
Mucosal melanomas are rare but usually present as locally aggressive tumors, mainly of the hard palate and gingiva. Bony tumors, including osteosarcoma of the mandible or maxilla and odontogenic tumors such as ameloblastoma, can present within the oral cavity and may be mistaken for a mucosal lesion if there is surface ulceration.
Clinical presentation and evaluation
Despite easy self-examination and physical examination, patients often present with advanced-stage disease. A comprehensive head and neck examination is mandatory in patients with suspected oral cavity cancer. Visual inspection and palpation allow an accurate impression of the extent of the disease, the third dimension of tumor, the presence of bone invasion, or skin breakdown. Appropriate documentation with drawings and photographic records of the tumor are useful in staging, decision making, and further follow-up. The clinical TNM stage should be recorded at first encounter and modified as evaluation progresses.
The initial workup consists of diagnosis by biopsy. Accessible lesions may be adequately biopsied in the clinic using punch forceps, core needle biopsy, or fine-needle aspiration. Some patients will require examination under general anesthesia to access posteriorly located lesions or complete a physical examination limited by pain and trismus. Radiographic imaging is crucial for evaluation of the relation of the tumor to adjacent bone and for assessing regional lymph nodes. Computed tomography (CT) is the method of choice for evaluation of bone and neck nodes, especially early cortical involvement and extracapsular nodal spread. MRI provides complementary information about the extent of soft tissue and perineural invasion, and is also helpful for evaluating the extent of medullary bone involvement because adult marrow is normally replaced by fat. Most patients with oral cancer are not at risk for distant metastases, and therefore the role of positron emission tomography (PET) in initial assessment is debatable. However, a preoperative PET scan may be useful as a baseline if adjuvant treatment is anticipated, and a PET scan will be used for radiation therapy planning (although this is undertaken differently from a diagnostic PET scan). Patients with locally advanced tumors require appropriate multidisciplinary consultations with the reconstructive surgeon, medical specialists for presurgical optimization, dental professionals, speech and swallowing pathologists, and behavioral therapists for smoking cessation and other lifestyle alterations.
The TNM system is the most widely accepted prognostic system, owing to its relatively simple design and user-friendliness. The clinical staging of the oral cavity tumors consists of primary tumor characteristics, the neck, and assessment for distant metastases ( Table 1 ). This information allows TNM stage grouping for the tumor ( Table 2 ). The basic elements in staging of the primary site are the tumor size and invasion of deep structures. Advanced disease is defined by invasion of structures such as medullary bone, deep muscle of the tongue, maxillary sinus, and skin for T4a disease, or masticator space, pterygoid plates, or skull base and/or encasement of the internal carotid artery for T4b disease. Lymphatic spread into the neck generally occurs in a stepwise, orderly, and predictable fashion. The lymph node echelons of the neck are described using the terminology standardized by the American Head and Neck Society Guidelines ( Fig. 3 ).
| T | Primary Tumor |
| TX | Primary tumor cannot be assessed |
| T0 | No evidence of primary tumor |
| Tis | Carcinoma in situ |
| T1 | Tumor 2 cm or less in greatest dimension |
| T2 | Tumor more than 2 cm but not more than 4 cm in greatest dimension |
| T3 | Tumor more than 4 cm in greatest dimension |
| T4a (lip) | Tumor invades through cortical bone, inferior alveolar nerve, floor of mouth, or skin (chin or nose) |
| T4a (oral cavity) | Tumor invades through cortical bone, into deep/extrinsic muscle of tongue (genioglossus, hyoglossus, palatoglossus, and styloglossus), maxillary sinus, or skin of face |
| T4b (lip and oral cavity) | Tumor invades masticator space, pterygoid plates, or skull base; or encases internal carotid artery |
| N | Regional Lymph Nodes |
| NX | Regional lymph nodes cannot be assessed |
| N0 | No regional lymph node metastasis |
| N1 | Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension |
| N2 | Metastasis as specified in N2a, 2b, 2c below |
| N2a | Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension |
| N2b | Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension |
| N2c | Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension |
| N3 | Metastasis in a lymph node more than 6 cm in greatest dimension |
| M | Distant Metastasis |
| MX | Distant metastasis cannot be assessed |
| M0 | No distant metastasis |
| M1 | Distant metastasis |
| Stage | T | N | M |
|---|---|---|---|
| 0 | Tis | N0 | M0 |
| I | T1 | N0 | M0 |
| II | T2 | N0 | M0 |
| III | T3 | N0 | M0 |
| T1 | N1 | M0 | |
| T2 | N1 | M0 | |
| T3 | N1 | M0 | |
| IVA | T4a | N0 | M0 |
| T4a | N1 | M0 | |
| T1 | N2 | M0 | |
| T2 | N2 | M0 | |
| T3 | N2 | M0 | |
| T4a | N2 | M0 | |
| IVB | Any T | N3 | M0 |
| T4b | Any N | M0 | |
| IVC | Any T | Any N | M1 |
Knowledge of the patterns of nodal metastasis has practical implications in the design of neck dissection for patients with oral cancer. The patient with a clinically negative neck is at highest risk of metastasis to levels I to III. Skip metastases to level IV do occur, especially in cancer of the anterior tongue. Metastases to level V are extremely rare (1%), even in patients with clinically positive neck. Oral tongue tumors have the greatest propensity of all oral cancers for metastasis to the neck, and tumor thickness ( Fig. 4 ) is a major predictor of the risk of nodal metastasis.
Treatment
Surgical resection is the treatment of choice for SCCOC. Resection allows accurate pathologic staging, with information about the status of margins, tumor spread, and histopathologic characteristics, which can then be used to inform subsequent management based on assessment of risk versus benefit. Adjuvant radiotherapy with or without chemotherapy is used for specific indications in locoregionally advanced tumors. A multidisciplinary team is essential to ensuring a favorable outcome. Multiple factors are taken into account in selecting treatment for an individual patient. The risk of treatment-related complications should be assessed based on physiologic age, comorbid conditions (eg, cardiopulmonary status), lifestyle (smoking or alcohol), surgical resectability, and patient expectations.
Surgical Management
A detailed description of surgical technique for the management of oral cavity cancers is beyond the scope of this article, and the reader is referred to specialized texts for this information. Broad principles of surgical management are discussed, including access to the oral cavity, management of the mandible, management of neck nodes, and reconstruction of oral cavity surgical defects.
Surgical access
The transoral approach is usually used for premalignant lesions and small, superficial tumors of the anterior floor of the mouth, alveolus, and tongue. A more invasive approach becomes necessary for posteriorly located tumors or if there are limitations resulting from trismus or inadequate surgical exposure ( Fig. 5 ). The lip-splitting paramedian mandibulotomy approach is used for larger posteriorly located tumors of the tongue. The upper cheek flap and midfacial degloving approaches are useful for gaining access to the maxilla.
