The evaluation should include a complete medical history with an emphasis on the head and neck region. Although the typical patient profile is changing, the patient is usually an older male with a history of smoking and/or alcohol use with a non-resolving oral cavity/tongue lesion. A history of accidental trauma to the region is often reported by patients. The most commonly reported symptom is localized pain. Dysphagia, weight loss, dysarthria, and odynophagia are also common. The patient’s ability to tolerate his usual diet should be addressed. Any history of recently noticed neck masses or nodules is also fundamental, as this may represent locoregional metastatic disease. Recent onset of unilateral nasal obstruction, unilateral hearing loss, or unilateral otalgia is worrisome for disease extension beyond the oral cavity to the pharyngeal region.

The examination should include a complete physical exam with an emphasis on the head and neck region. The neck should be thoroughly examined for palpable lymphadenopathy, especially the submental, submandibular, and jugulodigastric regions. An invasive examination of the patient’s oral cavity should be performed. This includes a detailed description of the lesion or mass in question, including but not limited to location, general appearance, color, shape, margins, and the presence or absence of ulceration. Thorough palpation should also be performed with the intention of assessing the regions of the tongue that are involved or spared by the tumor. Palpation of the base of the tongue/vallecula region is also encouraged, as it may reveal asymmetrically indurated or protruding areas. Several specific clinical signs and symptoms may offer insight into the extent of tumor extension.

Hypoglossal nerve or tongue muscle involvement may manifest as ipsilateral tongue deviation. Lingual nerve involvement may manifest as an altered sensation in the tongue. Inferior alveolar nerve involvement manifests as numbness in the chin, lower lip, and/or mandibular teeth and indicates more advanced disease. Lastly, an awake fiberoptic examination of the patient’s upper airway is also recommended, as the usual risk factors for oral cavity carcinoma are common to other head and neck sites. A flexible nasolaryngoscopy under local anesthesia excludes grossly suspicious pathology in the nasal cavity, nasopharynx, oropharynx, hypopharynx, and larynx.

In addition to the clinical examination, other studies are necessary to diagnose, characterize, and appropriately stage the disease. In the case of the tongue, lesions are usually readily accessible and, therefore, amenable to incisional biopsy or punch biopsy under local anesthesia in a clinic setting. In the case of the base of the tongue lesions, if not accessible trans-orally, tissue diagnosis may be obtained during flexible laryngoscopy or under direct visualization with general anesthesia. In the case of patients with gross neck lymphadenopathy, ultrasound-guided fine-needle aspiration (FNA) biopsy is also an option.

Computed tomography (CT) scan of the neck with intravenous contrast is also part of the diagnostic workup. This will provide information regarding tumor size, location, extension, and radiologic appearance of the draining neck lymph nodes. In the case of advanced disease at presentation, further imaging of the chest with a CT scan or whole-body positron emission tomography (PET)/CT is usually done to rule out distant metastatic spread of disease.

The management of tongue carcinoma is primarily surgical, with radiation also having an important role mainly in advanced disease, poor surgical candidates, unresectable disease, and importantly, as an adjuvant to surgery in some cases. Unless there is a clear contraindication for surgery or the tumor is unresectable, surgery should be offered as primary treatment for tongue squamous cell carcinoma. The ultimate goal of treatment is complete cure while minimizing therapy sequela and preserving functionality.  

In general, early-stage tongue carcinoma (T1 or T2) can be treated successfully with single-modality therapy, namely surgery or radiation. However, when long-term morbidity of treatment, cost, and other factors are considered, surgery is recommended upfront.

On the other hand, patients with advanced disease (T3 or T4) have a poor response to single-modality treatment. Two independent clinical trials found that postoperative adjuvant chemoradiation offered improved survival when compared to single-modality therapy in these patients.[16] Therefore, if feasible, surgery and postoperative chemoradiation would be the optimal treatment plan for a patient with advanced disease. Chemoradiation up-front typically offers poor locoregional control, negatively impacting prognosis, and frequently leads to more destructive salvage surgery without the possibility of adjuvant radiation. When indicated, the standard of care for radiation therapy doses in patients with oral cavity cancer range from 60-65Gy in 30-35 treatment fractions.

Surgical interventions range from simple wide local excision and primary closure in small tumors to composite resections of the tongue/floor of mouth/mandible in advanced tumors with the need for locoregional flaps or microvascular free flap reconstruction. Regardless of the extent of surgery required, several fundamental cancer surgery principles should be followed for the best oncologic outcomes. The primary tumor resection should include at least a 1cm margin of resection when possible. Intraoperative frozen sections should be sent to pathologically confirm disease-free margins. If a significant functional deficit is anticipated, reconstruction with free vascularized tissue (free flap) should be offered when available, as this offers optimal functional outcomes after surgery in terms of swallow and speech function. The radial forearm free flap and the anterolateral thigh free flap are the two most commonly used free flaps for tongue reconstruction. The fibula free flap is also commonly used when large resections are needed, and mandibular reconstruction is necessary. Although free flaps are the mainstay of reconstructive options, locoregional pedicled flaps are a viable alternative when free flap reconstruction is contraindicated, not available, or has failed. These include the submental island flap, latissimus dorsi pedicled flap, and the pectoralis major myocutaneous flap. When compared to free flaps, these have the advantage of shorter operative times, decreased donor site morbidity, and good reliability.

Regarding the base of tongue HPV-related squamous cell carcinoma, the treatment algorithm has completely shifted during the last decades. Trans-oral robotic surgery has a role mainly in early-stage disease, while advanced tumors in this region are usually treated with primary radiation and chemotherapy, given its excellent response.[6][15] This observation, while opposite to its HPV-negative counterpart, is well documented and supported in the literature and has led to research looking at de-intensifying treatment for this specific HPV-positive patient sub-group.[7]

Management of the neck is essential, as recurrence or persistence of disease in the neck after primary therapy confers a poor prognosis. The tongue has a rich network of lymphatics that drain to neck levels I-III, which is the usual pattern of spread when these tumors metastasize. As stated before, the depth of invasion is a major prognostic indicator. Studies show that tongue tumors with anywhere between three and eight millimeters of the depth of invasion have up to a 40%-50% risk of occult nodal metastasis and up to 65% overall incidence of nodal metastasis.[17] Because without a complete histopathological analysis, the true depth of invasion of a tongue tumor cannot be determined, many head and neck oncologic surgeons argue that any malignant tongue lesion with grossly palpable depth to it will likely exceed this depth mark. With this in mind, the majority of patients that present with a primary tongue squamous cell carcinoma must be offered a neck dissection to pathologically rule out occult nodal metastasis (termed an elective neck dissection) or to surgically remove the clinically evident nodal disease. When there is no clinical or radiologic evidence of neck disease but an ipsilateral elective neck dissection is warranted, a selective dissection of levels I-III, also called a supraomohyoid neck dissection, is usually employed.[14] On the other hand, when there is gross evidence of neck disease either preoperatively or intraoperatively, an ipsilateral modified radical neck dissection is recommended.

Patients with pathologic confirmation of disease presence in the locoregional lymph nodes, most of the time, require additional treatment after surgery to achieve a cure. Usually, this consists of a combination of cisplatin-based chemotherapy and radiation. Positive surgical margins and pathologically confirmed extranodal extension of the disease are two absolute indications for adjuvant chemoradiation. Other indications for radiation therapy include advanced stage (T3 or T4) disease, close surgical margin, lymphovascular invasion, perineural invasion, and two or more positive neck lymph nodes. 

Immunotherapeutic agents, specifically tyrosine kinase inhibitors and PD-1 inhibitors, are now being used more frequently in combination with cisplatin-based chemotherapy or alone, and there is ongoing clinical research regarding their potential benefits in head and neck squamous cell carcinoma.

Patients with known distant metastatic spread of disease are not surgical candidates and are offered primary chemoradiation, chemotherapy, or immunotherapy.

• Squamous cell carcinoma
• Leukoplakia
• Carcinoma in situ
• Sarcoma
• Rhabdomyosarcoma
• Lymphoma
• Rhabdomyoma
• Neurofibroma
• Pyogenic granuloma
• Papilloma
• Vascular or lymphatic malformation
• Lingual thyroid
• Dermoid cyst
• Epidermoid cyst

Staging

The American Joint Committee on Cancer uses the TNM system for staging tumors of the head and neck region by the site. It was recently updated to incorporate the prognostic impact of the presence of extranodal extension. Accordingly, clinically evident extranodal extension upstages the N-stage of a tumor to N3b.[10][18]

T-stage is classified as follows:

• T0: No evidence of primary tumor
• Tis: Carcinoma in situ
• T1: Tumor 2cm or less with a depth of invasion (DOI) less than or equal to 5mm
• T2: Tumor 2cm or less with DOI more than 5mm OR tumor more than 2cm but less than or equal to 4cm
• T3: Tumor more than 2cm but less than or equal to 4cm with DOI more than 10mm OR tumor more than 4cm with DOI less than or equal to 10mm
• T4a: Tumor more than 4cm with DOI more than 10mm OR invades adjacent structures only (skin of the face, maxillary sinus, cortical bone of maxilla or mandible)
• T4b: Tumor invades masticator space, pterygoid plates, skull base, and/or encases the internal carotid artery. 

N-stage or clinical nodal stage is classified as follows:

• N0: No regional nodes metastasis.
• N1: Metastasis in a single ipsilateral lymph node 3cm or less in the greatest dimension - negative extranodal extension (ENE)
• N2a: Metastasis in a single ipsilateral lymph node more than 3cm but not larger than 6cm in the greatest dimension, negative ENE
• N2b: Metastasis in multiple ipsilateral lymph nodes, none more than 6cm in greatest dimension, negative ENE
• N2c: Metastasis in bilateral or contralateral lymph node(s), none more than 6cm in greatest dimension, negative ENE
• N3a: Metastasis in any lymph node more than 6cm in the greatest dimension, negative ENE
• N3b: Metastasis in a lymph node with clinically overt positive ENE

M-stage is classified as follows:

• MX: Distant metastasis cannot be assessed
• M0: No distant metastasis
• M1: Distant metastasis

A recent study using the Surveillance, Epidemiology, and End Results (SEER) database looked at the incidence and survival of oral tongue squamous cell carcinoma. They report that although the incidence is increasing for both oral tongue SCCA and oropharyngeal squamous cell carcinoma, survival has also significantly improved.[19] 

The study shows that from 1976 to 2015, oral tongue SCCA and oropharyngeal squamous cell carcinoma both showed the highest absolute increase in survival, with conditional survival of over 90% for both diseases independent of the treatment.

Complications of surgery are multiple and include bleeding, infection, and orocutaneous fistula. When a free or pedicled flap is employed, complications include donor site infection, bleeding, and partial or complete flap loss or infection. Depending on the extent of resection and adequacy of reconstruction, there may be function-related complications such as impaired speech, dysphagia, and odynophagia. A gastrostomy is frequently needed at the time of surgery if speech and swallow rehabilitation are anticipated to be problematic or prolonged. A tracheostomy is also frequently employed if significant oral cavity and pharyngeal airway edema are anticipated in the immediate postoperative period.

Radiation therapy complications include oral/pharyngeal mucositis, skin damage, cellulitis, dysgeusia, xerostomia, fibrosis, and oral mucosal neuropathy. One of the most troublesome complications of radiation therapy in this region is mandibular osteoradionecrosis (ORN). This may require surgical intervention for curettage, and in severe cases, segmental mandibulectomy of the affected region and reconstruction. Although hyperbaric oxygen therapy is sometimes given to treat mandibular ORN, some surgeons argue this may increase the probability of malignancy recurrence or may catalyze the growth of microscopic persistent disease. No high-level evidence studies to date have conclusively demonstrated this correlation, but anecdotal evidence exists, and the decision remains clinician-dependent.

Common radiation side effects in the neck region include post-radiation fibrosis, frozen neck, neuropathy, and hypothyroidism, among others. Symptomatic esophageal stenosis due to post-radiation fibrosis is not uncommon and may manifest even years after radiation therapy.

One of the most feared complications of advanced-stage head and neck cancer is carotid blowout. This usually presents with life-threatening hemorrhage and used to be almost uniformly fatal. However, mortality today is close to 60% due to major surgical and endovascular advances. Nonetheless, periprocedural morbidity is high and may include re-bleeding and stroke.

Small tumors frequently require minimal reconstruction with good preservation of oral function. However, in more advanced disease, rehabilitation becomes a challenge. Ideal rehabilitation includes restoring the external appearance, dentition, mastication, speech, and swallow function. With more advanced reconstructions leading to loss of part of the mandible, restoration of dentition and masticatory function was classically achieved with the use of removable prosthesis with suboptimal results. This has now been largely replaced with the use of dental implants in patients with free flap mandibular reconstructions. Optimal rehabilitation in the oral cancer patient will thus rely on effective teamwork and communication between speech and language pathologists, dental specialists, and oncologic surgeons.

The preoperative orientation of the patient about to undergo oral cavity surgery and reconstruction is of paramount importance. The patient and family members should understand that surgery will be the first step in a long rehabilitation and follow up process. Tobacco and/or alcohol cessation counseling should be offered to all patients, as patients who continue to smoke or drink during treatment have a very high likelihood of recurrence. Medical therapy for cessation should be offered. If not available, the clinician should refer the patient to a medical colleague that can provide such treatment.

Patients with oral/tongue carcinoma should receive care from an interprofessional team, ideally in an institution that allows for efficient communication and minimal delays in management. Although the surgeon, the oncologist, and the radiation oncologist obviously play an integral role, many of these patients benefit pre and postoperatively from evaluation and treatment from dental specialists, endocrinologists, nutritionists, primary clinicians, and speech pathologists, among others.

Lastly, cancers of the oral cavity are frequently noticed by the patients themselves, primary care clinicians, or dentists. It is essential for these patients who have early-stage tumors to reach the hands of a head and neck oncologic surgeon in a timely manner. Unfortunately, despite an overall increased survival, many patients still present with advanced-stage disease. Patients with early-stage disease usually have good outcomes, and survival is excellent, but prognosis worsens in those presenting late with large tumors or locoregional metastasis. Thus, any oral cavity lesion that persists or worsens after two weeks warrants prompt biopsy and evaluation by a head and neck specialist.