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Lip and Oral Cavity Cancer

Summary Type: Treatment
Summary Audience: Health professionals
Summary Language: English
Summary Description: Expert-reviewed information summary about the treatment of lip and oral cavity cancer.


Lip and Oral Cavity Cancer

General Information

Note: Separate PDQ summaries on Prevention of Oral Cancer and Screening for Oral Cancer are also available.

The oral cavity extends from the skin-vermilion junctions of the anterior lips to the junction of the hard and soft palates above and to the line of circumvallate papillae below and is divided into the following specific areas:

  • Lip.
  • Anterior two thirds of tongue.
  • Buccal mucosa.
  • Floor of mouth.
  • Lower gingiva.
  • Retromolar trigone.
  • Upper gingiva.
  • Hard palate.

The main routes of lymph node drainage are into the first station nodes (i.e., buccinator, jugulodigastric, submandibular, and submental). Sites close to the midline often drain bilaterally. Second station nodes include the parotid, jugular, and the upper and lower posterior cervical nodes.

Early cancers (stage I and stage II) of the lip and oral cavity are highly curable by surgery or by radiation therapy, and the choice of treatment is dictated by the anticipated functional and cosmetic results of treatment and by the availability of the particular expertise required of the surgeon or radiation oncologist for the individual patient.1,2,3 The presence of a positive margin or a tumor depth >5 mm significantly increases the risk of local recurrence and suggests that combined modality treatment may be beneficial.4,5,

Advanced cancers (stage III and stage IV) of the lip and oral cavity represent a wide spectrum of challenges for the surgeon and radiation oncologist. Except for patients with small T3 lesions and no regional lymph node and no distant metastases or who have no lymph nodes >2 cm, for whom treatment by radiation therapy alone or surgery alone might be appropriate, most patients with stage III or stage IV tumors are candidates for treatment by a combination of surgery and radiation therapy.2 Furthermore, because local recurrence and/or distant metastases are common in this group of patients, they should be considered for clinical trials. Such trials evaluate the potential role of radiation modifiers or combination chemotherapy combined with surgery and/or radiation therapy.

Patients with head and neck cancers have an increased chance of developing a second primary tumor of the upper aerodigestive tract.6,7 A study has shown that daily treatment of these patients with moderate doses of isotretinoin (13-cis -retinoic acid) for 1 year can significantly reduce the incidence of second tumors. No survival advantage has yet been demonstrated, however, in part due to recurrence and death from the primary malignancy. Additional trials are ongoing.8,

The rate of curability of cancers of the lip and oral cavity varies depending on the stage and specific site. Most patients present with early cancers of the lip, which are highly curable by surgery or by radiation therapy with cure rates of 90% to 100%. Small cancers of the retromolar trigone, hard palate, and upper gingiva are highly curable by either radiation therapy or surgery, with survival rates of as much as 100%. Local control rates of as much as 90% can be achieved with either radiation therapy or surgery in small cancers of the anterior tongue, the floor of the mouth, and buccal mucosa.9,

Moderately advanced and advanced cancers of the lip also can be controlled effectively by surgery or radiation therapy or a combination of these. The choice of treatment is generally dictated by the anticipated functional and cosmetic results of the treatment. Moderately advanced lesions of the retromolar trigone without evidence of spread to cervical lymph nodes are usually curable and have shown local control rates of as much as 90%; such lesions of the hard palate, upper gingiva, and buccal mucosa have a local control rate of as much as 80%. In the absence of clinical evidence of spread to cervical lymph nodes, moderately advanced lesions of the floor of the mouth and anterior tongue are generally curable, with survival rates of as much as 70% and 65%, respectively.9,10,



1 Cummings CW, Fredrickson JM, Harker LA, et al.: Otolaryngology - Head and Neck Surgery. Saint Louis, Mo: Mosby-Year Book, Inc., 1998.

2 Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott-Raven, 1999.

3 Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997.

4 Jones KR, Lodge-Rigal RD, Reddick RL, et al.: Prognostic factors in the recurrence of stage I and II squamous cell cancer of the oral cavity. Arch Otolaryngol Head Neck Surg 118 (5): 483-5, 1992.

5 Po Wing Yuen A, Lam KY, Lam LK, et al.: Prognostic factors of clinically stage I and II oral tongue carcinoma-A comparative study of stage, thickness, shape, growth pattern, invasive front malignancy grading, Martinez-Gimeno score, and pathologic features. Head Neck 24 (6): 513-20, 2002.

6 Day GL, Blot WJ: Second primary tumors in patients with oral cancer. Cancer 70 (1): 14-9, 1992.

7 van der Tol IG, de Visscher JG, Jovanovic A, et al.: Risk of second primary cancer following treatment of squamous cell carcinoma of the lower lip. Oral Oncol 35 (6): 571-4, 1999.

8 Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 323 (12): 795-801, 1990.

9 Wallner PE, Hanks GE, Kramer S, et al.: Patterns of Care Study. Analysis of outcome survey data-anterior two-thirds of tongue and floor of mouth. Am J Clin Oncol 9 (1): 50-7, 1986.

10 Takagi M, Kayano T, Yamamoto H, et al.: Causes of oral tongue cancer treatment failures. Analysis of autopsy cases. Cancer 69 (5): 1081-7, 1992.

Cellular Classification

Most head and neck cancers are of the squamous cell variety and may be preceded by various precancerous lesions. Minor salivary gland tumors are not uncommon in these sites. Specimens removed from the lesions may show the carcinomas to be noninvasive, in which case the term carcinoma in situ is applied. An invasive carcinoma will be either well-differentiated, moderately well-differentiated, poorly differentiated or undifferentiated.

Tumor grading is recommended using Broder’s classification (Tumor Grade [G]):

  • G1: well-differentiated.
  • G2: moderately well-differentiated.
  • G3: poorly-differentiated.
  • G4: undifferentiated.1,

No statistically significant correlation between degree of differentiation and the biologic behavior of the cancer exists; however, vascular invasion is a negative prognostic factor.2,

Other tumors of glandular epithelium, odontogenic apparatus, lymphoid tissue, soft tissue, and bone and cartilage origin require special consideration and are not included in this section of PDQ. Reference to the World Health Organization nomenclature is recommended.

The term leukoplakia should be used only as a clinically descriptive term meaning that the observer sees a white patch that does not rub off, the significance of which depends on the histologic findings. Leukoplakia can range from hyperkeratosis to an actual early invasive carcinoma or may only represent a fungal infection, lichen planus, or other benign oral disease.



1 Bansberg SF, Olsen KD, Gaffey TA: High-grade carcinoma of the oral cavity. Otolaryngol Head Neck Surg 100 (1): 41-8, 1989.

2 Close LG, Brown PM, Vuitch MF, et al.: Microvascular invasion and survival in cancer of the oral cavity and oropharynx. Arch Otolaryngol Head Neck Surg 115 (11): 1304-9, 1989.

Stage Information

The staging systems are all clinical staging and are based on the best possible estimate of the extent of disease before treatment. The assessment of the primary tumor is based on inspection and palpation when possible and by both indirect mirror examination and direct endoscopy when necessary. The tumor must be confirmed histologically, and any other pathologic data obtained on biopsy may be included. The appropriate nodal drainage areas are examined by careful palpation. Information from diagnostic imaging studies may be used in staging. Magnetic resonance imaging offers an advantage over computed tomographic scans in the detection and localization of head and neck tumors and in the distinction of lymph nodes from blood vessels.1 If a patient relapses, complete restaging must be done to select the appropriate additional therapy.2,3,

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification.4

TNM definitions

    Primary tumor (T)
  • TX: Primary tumor cannot be assessed
  • T0: No evidence of primary tumor
  • Tis: Carcinoma in situ
  • T1: Tumor ≤2 cm in greatest dimension
  • T2: Tumor >2 cm but ≤4 cm in greatest dimension
  • T3: Tumor >4 cm in greatest dimension
  • T4: (lip) Tumor invades through cortical bone, inferior alveolar nerve, floor of mouth, or skin of face, i.e., chin or nose
    • T4a: (oral cavity) Tumor invades adjacent structures (e.g., through cortical bone, into deep [extrinsic] muscle of tongue [genioglossus, hyoglossus, palatoglossus, and styloglossus], maxillary sinus, and skin of face)
    • T4b: Tumor invades masticator space, pterygoid plates, or skull base and/or encases internal carotid artery

    Superficial erosion alone of bone/tooth socket by gingival primary is not sufficient to classify a tumor as T4.

    Regional lymph nodes (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
  • N2: Metastasis in a single ipsilateral lymph node, >3 cm but ≤6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, ≤6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, ≤6 cm in greatest dimension
    • N2a: Metastasis in a single ipsilateral lymph node >3 cm but ≤6 cm in dimension
    • N2b: Metastasis in multiple ipsilateral lymph nodes, ≤6 cm in greatest dimension
    • N2c: Metastasis in bilateral or contralateral lymph nodes, ≤6 cm in greatest dimension
  • N3: Metastasis in a lymph node >6 cm in greatest dimension

In clinical evaluation, the actual size of the nodal mass should be measured and allowance should be made for intervening soft tissues. Most masses >3 cm in diameter are not single nodes but are confluent nodes or tumors in soft tissues of the neck. The 3 stages of clinically positive nodes are: N1, N2, and N3. The use of subgroups a, b, and c is not required but is recommended. Midline nodes are considered homolateral nodes.

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

AJCC stage groupings

    Stage 0
  • Tis, N0, M0
    Stage I
  • T1, N0, M0
    Stage II
  • T2, N0, M0
    Stage III
  • T3, N0, M0
  • T1, N1, M0
  • T2, N1, M0
  • T3, N1, M0
    Stage IVA
  • T4a, N0, M0
  • T4a, N1, M0
  • T1, N2, M0
  • T2, N2, M0
  • T3, N2, M0
  • T4a, N2, M0
    Stage IVB
  • Any T, N3, M0
  • T4b, any N, M0
    Stage IVC
  • Any T, any N, M1


1 Consensus conference. Magnetic resonance imaging. JAMA 259 (14): 2132-8, 1988.

2 Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott-Raven, 1999.

3 Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997.

4 Lip and oral cavity. In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 23-32.

Treatment Option Overview

Depending on the site and extent of the primary tumor and the status of the lymph nodes, the treatment of lip and oral cavity cancer may be by surgery alone, radiation therapy alone, or a combination of these. Some general considerations are as follows.1,2,3,4,5,

For lesions of the oral cavity, surgery must adequately encompass all of the gross as well as the presumed microscopic extent of the disease. If regional nodes are positive, cervical node dissection is usually done in continuity. With modern approaches, the surgeon can successfully ablate large posterior oral cavity tumors and with reconstructive methods can achieve satisfactory functional results. Prosthodontic rehabilitation is important, particularly in early-stage cancers, to assure the best quality of life.

Radiation therapy for lip and oral cavity cancers can be by external-beam radiation therapy or interstitial implantation alone, but for many sites the use of both modalities produces better control and functional results. Small superficial cancers can be very successfully treated by local implantation using any one of several radioactive sources, by intraoral cone radiation therapy, or by electrons. Larger lesions are frequently managed using external-beam radiation therapy to include the primary site and regional lymph nodes even if they are not clinically involved. Supplementation with interstitial radiation sources may be necessary to achieve adequate doses to large primary tumors and/or bulky nodal metastases. A review of published clinical results of radical radiation therapy for head and neck cancer suggests a significant loss of local control when the administration of radiation therapy was prolonged; therefore, lengthening of standard treatment schedules should be avoided whenever possible.6,7,

Early cancers (stage I and stage II) of the lip, floor of mouth, and retromolar trigone are highly curable by surgery or radiation therapy. The choice of treatment is dictated by the anticipated functional and cosmetic results and by the availability of the particular expertise required of the surgeon or radiation oncologist for the individual patient. Advanced cancers (stage III and stage IV) of the lip, floor of mouth, and retromolar trigone represent a wide spectrum of challenges for the surgeon and radiation oncologists. Except for patients with small T3 lesions and no regional lymph node and no distant metastases or who have no lymph nodes >2 cm, for whom treatment by radiation therapy alone or surgery alone might be appropriate, most patients with stage III or stage IV tumors are candidates for treatment by a combination of surgery and radiation therapy. Furthermore, because local recurrence and/or distant metastases are common in this group of patients, they should be considered for clinical trials evaluating the following: the potential role of radiation modifiers to improve local control or decrease morbidity; or, the role of combinations of chemotherapy with surgery and/or radiation therapy both to improve local control and to decrease the frequency of distant metastases.

Early cancers of the buccal mucosa are equally curable by radiation therapy or by adequate excision. Patient factors and local expertise influence the choice of treatment. Larger cancers require composite resection with reconstruction of the defect by pedicle flaps.

Early lesions (T1 and T2) of the anterior tongue may be managed by surgery or by radiation therapy alone. Both modalities produce 70% to 85% cure rates in early lesions. Moderate excisions of tongue, even hemiglossectomy, can often result in surprisingly little speech disability provided the wound closure is such that the tongue is not bound down. If, however, the resection is more extensive, problems may include aspiration of liquids and solids and difficulty in swallowing in addition to speech difficulties. Occasionally, patients with tumor of the tongue require almost total glossectomy. Large lesions generally require combined surgical and radiation treatment. The control rates for larger lesions are about 30% to 40%. According to clinical and radiological evidence of involvement, cancers of the lower gingiva that are exophytic and amenable to adequate local excision may be excised to include portions of bone. More advanced lesions require segmental bone resection, hemimandibulectomy, or maxillectomy, depending on the extent of the lesion and its location.

Early lesions of the upper gingiva or hard palate without bone involvement can be treated with equal effectiveness by surgery or by radiation therapy alone. Advanced infiltrative and ulcerating lesions should be treated by a combination of radiation therapy and surgery. Most primary cancers of the hard palate are of minor salivary gland origin. Primary squamous cell carcinoma of the hard palate is uncommon, and these tumors generally represent invasion of squamous cell carcinoma arising on the upper gingiva, which is much more common. Thus, management of squamous cell carcinoma of the upper gingiva and hard palate are usually considered together. Surgical treatment of cancer of the hard palate usually requires excision of underlying bone producing an opening into the antrum. This defect can be filled and covered with a dental prosthesis, a maneuver that restores satisfactory swallowing and speech.

Patients who smoke while on radiation therapy appear to have lower response rates and shorter survival durations than those who do not;8 therefore, patients should be counseled to stop smoking before beginning radiation therapy. Dental status evaluation should be performed prior to therapy to prevent late sequelae.

The designations in PDQ that treatments are “standard” or “under clinical evaluation” are not to be used as a basis for reimbursement determinations.



1 Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott-Raven, 1999.

2 Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997.

3 Myers EN, Suen JY, eds.: Cancer of the Head and Neck. 3rd ed. Philadelphia, Pa: Saunders, 1996.

4 Freund HR: Principles of Head and Neck Surgery. 2nd ed. New York, NY: Appleton-Century-Crofts, 1979.

5 Lore JM: An Atlas of Head and Neck Surgery. 3rd ed. Philadelphia, Pa: Saunders, 1988.

6 Fowler JF, Lindstrom MJ: Loss of local control with prolongation in radiotherapy. Int J Radiat Oncol Biol Phys 23 (2): 457-67, 1992.

7 Langendijk JA, de Jong MA, Leemans ChR, et al.: Postoperative radiotherapy in squamous cell carcinoma of the oral cavity: the importance of the overall treatment time. Int J Radiat Oncol Biol Phys 57 (3): 693-700, 2003.

8 Browman GP, Wong G, Hodson I, et al.: Influence of cigarette smoking on the efficacy of radiation therapy in head and neck cancer. N Engl J Med 328 (3): 159-63, 1993.

Stage I Lip and Oral Cavity Cancer

Surgery and/or radiation therapy may be used, depending on the exact site.1,2,

Small lesions of the lip

Standard treatment options:

  • Surgery and radiation therapy produce similar cure rates, and the method of treatment is dictated by the anticipated cosmetic and functional results.

Small anterior tongue lesions

Standard treatment options:

  1. Wide local excision is often used for small lesions that can be resected transorally.
  2. For larger T1 lesions, either surgery or radiation therapy is an acceptable treatment. Interstitial implantation alone or with external-beam radiation therapy should be considered. Consideration should be given to irradiating the neck.

Small lesions of the buccal mucosa

Standard treatment options:

  1. Lesions <1 cm in diameter may be managed by surgery alone if the commissure is not involved. If the commissure is involved, radiation therapy (including brachytherapy) should be considered.
  2. Larger T1 lesions may be treated by surgical excision with split-thickness skin graft or radiation therapy.

Small lesions of the floor of mouth

Standard treatment options:

  1. Surgery and radiation therapy produce similar cure rates for T1 lesions.
  2. In general for lesions <0.5 cm, excision alone is adequate if there is a margin of normal mucosa between the lesion and the gingiva.
  3. For larger lesions, surgery is often used if the lesion is attached to the periosteum, whereas radiation therapy is often used if the lesion encroaches on the tongue.

Small lesions of the lower gingiva

Standard treatment options:

  1. Small lesions may be treated by intraoral resection with or without a rim resection of bone and repaired with a split-thickness skin graft.
  2. Radiation therapy may be used for small lesions but results are generally better after surgery alone.

Small tumors of the retromolar trigone

Standard treatment options:

  1. For early lesions without detectable bone invasion, limited resection of the mandible is performed.
  2. If limited resection is not feasible, radiation therapy may be used initially with surgery reserved for radiation failure.

Small lesions of the upper gingiva and hard palate

Standard treatment options:

  1. Most small lesions are treated by surgical resection.
  2. Postoperative radiation therapy may be used if appropriate.


1 Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott-Raven, 1999.

2 Guerry TL, Silverman S Jr, Dedo HH: Carbon dioxide laser resection of superficial oral carcinoma: indications, technique, and results. Ann Otol Rhinol Laryngol 95 (6 Pt 1): 547-55, 1986 Nov-Dec.

Stage II Lip and Oral Cavity Cancer

Surgery and/or radiation therapy may be used, depending on the exact site.1,

Small lesions of the lip

Standard treatment options:

  1. Surgery is used for smaller T2 lesions on the lower lip if simple closure produces an acceptable cosmetic result.
  2. If a reconstructive surgical procedure is required, radiation therapy has the advantage of producing a relatively better functional and cosmetic result with intact skin and muscle innervation.
  3. Radiation therapy may include external-beam and/or interstitial techniques as appropriate.

Small anterior tongue lesions

Standard treatment options:

  1. Radiation therapy is usually selected for T2 lesions that have minimal infiltration to preserve speech and swallowing. Surgery is reserved for patients for whom radiation treatment failed. Neck dissection may be considered when primary brachytherapy is used.2,
  2. Deeply infiltrative lesions are best treated by surgery, radiation therapy, or a combination of both.

Small lesions of the buccal mucosa

Standard treatment options:

  1. Small T2 lesions (≤3 cm) are usually treated by radiation therapy.
  2. Large T2 lesions (>3 cm) may be treated by surgery, radiation therapy, or a combination of these, if indicated. Radiation therapy is often used if the lesion involves the commissure. Surgery is often used if tumor invades the mandible or maxilla.

Small lesions of the floor of mouth

Standard treatment options:

  1. For small T2 lesions (≤3 cm), surgery is often used if the lesion is attached to the periosteum, whereas radiation therapy is often used if the lesion encroaches on the tongue.
  2. For large T2 lesions (>3 cm), surgery and radiation therapy are alternative methods of treatment, the choice of which depends primarily on the expected extent of disability from surgery.
  3. External-beam radiation therapy with or without interstitial radiation therapy should be considered postoperatively for larger lesions.

Small lesions of the lower gingiva

Standard treatment options:

  1. Small lesions may be treated by intraoral resection with or without a rim resection of bone and repaired with a split-thickness skin graft.
  2. Radiation therapy may be used for small lesions, but results are generally better after surgery alone.

Small tumors of the retromolar trigone

Standard treatment options:

  1. For early lesions without detectable bone invasion, limited resection of the mandible is performed.
  2. If limited resection is not feasible, radiation therapy may be used initially with surgery reserved for radiation failure.

Small lesions of the upper gingiva and hard palate

Standard treatment options:

  • Most lesions are treated by surgical resection with postoperative radiation therapy as appropriate. A small study showed that radiation therapy may be used effectively as the sole treatment modality.3,


1 Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott-Raven, 1999.

2 Pernot M, Malissard L, Aletti P, et al.: Iridium-192 brachytherapy in the management of 147 T2N0 oral tongue carcinomas treated with irradiation alone: comparison of two treatment techniques. Radiother Oncol 23 (4): 223-8, 1992.

3 Yorozu A, Sykes AJ, Slevin NJ: Carcinoma of the hard palate treated with radiotherapy: a retrospective review of 31 cases. Oral Oncol 37 (6): 493-7, 2001.

Stage III Lip and Oral Cavity Cancer

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Surgery and/or radiation therapy are used, depending on the exact tumor site.1,2 Neoadjuvant chemotherapy, as given in clinical trials, has been used to shrink tumors and thereby render them more definitively treatable with either surgery or radiation. Neoadjuvant chemotherapy is given prior to the other modalities, as opposed to standard adjuvant chemotherapy, which is given after or during definitive therapy with radiation or after surgery. Many drug combinations have been used as neoadjuvant chemotherapy.3,4,5,6 Randomized prospective trials, however, have yet to demonstrate a benefit in either disease-free or overall survival for patients receiving neoadjuvant chemotherapy.7,

Advanced lesions of the lip

These lesions, including those involving bone, nerves, and lymph nodes, generally require a combination of surgery and radiation therapy. Such patients are appropriate candidates for clinical trials.

Standard treatment options:

  1. Surgery: A variety of surgical approaches can be used depending on the size and location of the lesion and the needs for reconstruction.
  2. Radiation therapy: A variety of radiation therapy techniques can be used as dictated by the size and location of the lesion. Options include external-beam radiation therapy with or without brachytherapy.

Treatment options under clinical evaluation:

  1. Clinical trials for advanced tumors evaluating the use of chemotherapy preoperatively, before radiation therapy, as adjuvant therapy after surgery, or as part of combined modality therapy are appropriate.3,4,5,6,8,9,10 Information about ongoing clinical trials is available from the NCI Web site.
  2. Superfractionated radiation therapy.11,

Moderately advanced (late T2, small T3) lesions of the anterior tongue

Standard treatment options:

  1. Minimally infiltrative lesions may be treated with external-beam radiation therapy with or without interstitial implant.
  2. Deeply infiltrative lesions may be treated with surgery with postoperative radiation therapy.2,

Advanced lesions of the buccal mucosa

Standard treatment options:

  1. Radical surgical resection alone.
  2. Radiation therapy alone.
  3. Surgical resection plus radiation therapy, generally postoperative.

Treatment options under clinical evaluation:

  • Clinical trials for advanced tumors evaluating the use of chemotherapy preoperatively, before radiation therapy, as adjuvant therapy after surgery, or as part of combined modality therapy are appropriate.3,4,5,6,8,9,10,12 Information about ongoing clinical trials is available from the NCI Web site.

Moderately advanced lesions of the floor of mouth

Standard treatment options:

  1. Surgery: Rim resection plus neck dissection or partial mandibulectomy with neck dissection as appropriate.
  2. Radiation therapy: External-beam radiation therapy alone or external-beam radiation therapy plus an interstitial implant.

Treatment options under clinical evaluation:

  1. Clinical trials for advanced tumors evaluating the use of chemotherapy preoperatively, before radiation therapy, as adjuvant therapy after surgery, or as part of combined modality therapy are appropriate.3,4,5,6,8,9,10,12 Information about ongoing clinical trials is available from the NCI Web site.
  2. Clinical trials using novel radiation therapy fractionation schemas.13,

Moderately advanced lesions of the lower gingiva

Standard treatment options:

  • Extensive lesions with moderate bone destruction and/or nodal metastases should be treated by combined radiation therapy and radical resection or by radical resection alone. Radiation therapy may be either preoperative or postoperative.

Advanced lesions of the retromolar trigone

Standard treatment options:

  • Surgical composite resection that may be followed by postoperative radiation therapy.

Treatment options under clinical evaluation:

  1. Clinical trials for advanced tumors evaluating the use of chemotherapy preoperatively, before radiation therapy, as adjuvant therapy after surgery, or as part of combined modality therapy are appropriate.3,4,5,6,8,9,10,12 Information about ongoing clinical trials is available from the NCI Web site.
  2. Clinical trials using novel radiation therapy fractionation schemas.13,

Moderately advanced lesions of the upper gingiva

Standard treatment options:

  1. Superficial lesions with extensive involvement of the gingiva, hard palate, or soft palate may be treated by radiation therapy alone.
  2. Deeply invasive lesions involving bone should be treated by a combination of surgery and radiation therapy.

Moderately advanced lesions of the hard palate

Standard treatment options:

  1. Superficial lesions with extensive involvement of the gingiva, hard palate, or soft palate may be treated by radiation therapy alone.
  2. Deeply invasive lesions involving bone should be treated by a combination of surgery and radiation therapy or by surgery alone.

Treatment options for management of lymph nodes: 1,

  • Patients with advanced lesions should have elective lymph node radiation therapy or node dissection. The risk of metastases to lymph nodes is increased by high-grade histology, large lesions, spread to involve the wet mucosa of the lip or the buccal mucosa in patients with recurrent disease, and invasion of muscle ( i.e., orbicularis oris).

Standard treatment options:

  1. Radiation therapy alone or neck dissection:
    • N1 (0-2 cm).
    • N2b or N3; all nodes <2 cm. (A combined surgical and radiation therapy approach should also be considered.)
  2. Radiation therapy and neck dissection:
    • N1 (2-3 cm), N2a, N3.
  3. Surgery followed by radiation therapy, indications for which are as follows:
    • Multiple positive nodes.
    • Contralateral subclinical metastases.
    • Invasion of tumor through the capsule of the lymph node.
    • N2b or N3 (1 or more nodes in each neck, as appropriate, >2 cm).
  4. Radiation therapy prior to surgery:
    • Large fixed nodes.

Treatment options under clinical evaluation (all stage III lesions):

  • Chemotherapy has been combined with radiation therapy in patients who have locally advanced disease that is surgically unresectable.8,10,14,15,

A meta-analysis of 63 randomized prospective trials published between 1965 and 1993 showed an 8% absolute survival advantage in the subset of patients receiving concomitant chemotherapy and radiation therapy.16,[Level of evidence: 2A] Patients receiving adjuvant or neoadjuvant chemotherapy had no survival advantage. Cost, quality of life, and morbidity data were not available; no standard regimen existed; and the trials were felt to be too heterogenous to provide definitive recommendations. The results of 18 ongoing trials may further clarify the role of concomitant chemotherapy and radiation therapy in the management of oral cavity cancer.

The best chemotherapy to use and the appropriate way to integrate the 2 modalities is still unresolved.17,

Similar approaches in the patient with resectable disease, in whom resection would lead to a major functional deficit, are also being explored in randomized trials but cannot be recommended at this time as standard.

Novel fractionation radiation therapy clinical trials are under clinical evaluation.13 Information about ongoing clinical trials is available from the NCI Web site.



1 Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott-Raven, 1999.

2 Franceschi D, Gupta R, Spiro RH, et al.: Improved survival in the treatment of squamous carcinoma of the oral tongue. Am J Surg 166 (4): 360-5, 1993.

3 Ervin TJ, Clark JR, Weichselbaum RR, et al.: An analysis of induction and adjuvant chemotherapy in the multidisciplinary treatment of squamous-cell carcinoma of the head and neck. J Clin Oncol 5 (1): 10-20, 1987.

4 Al-Kourainy K, Kish J, Ensley J, et al.: Achievement of superior survival for histologically negative versus histologically positive clinically complete responders to cisplatin combination in patients with locally advanced head and neck cancer. Cancer 59 (2): 233-8, 1987.

5 Adjuvant chemotherapy for advanced head and neck squamous carcinoma. Final report of the Head and Neck Contracts Program. Cancer 60 (3): 301-11, 1987.

6 Ensley J, Crissman J, Kish J, et al.: The impact of conventional morphologic analysis on response rates and survival in patients with advanced head and neck cancers treated initially with cisplatin-containing combination chemotherapy. Cancer 57 (4): 711-7, 1986.

7 Mazeron JJ, Martin M, Brun B, et al.: Induction chemotherapy in head and neck cancer: results of a phase III trial. Head Neck 14 (2): 85-91, 1992 Mar-Apr.

8 Al-Sarraf M, Pajak TF, Marcial VA, et al.: Concurrent radiotherapy and chemotherapy with cisplatin in inoperable squamous cell carcinoma of the head and neck. An RTOG Study. Cancer 59 (2): 259-65, 1987.

9 Browman GP, Cripps C, Hodson DI, et al.: Placebo-controlled randomized trial of infusional fluorouracil during standard radiotherapy in locally advanced head and neck cancer. J Clin Oncol 12 (12): 2648-53, 1994.

10 Merlano M, Benasso M, Corvò R, et al.: Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck. J Natl Cancer Inst 88 (9): 583-9, 1996.

11 Johnson CR, Khandelwal SR, Schmidt-Ullrich RK, et al.: The influence of quantitative tumor volume measurements on local control in advanced head and neck cancer using concomitant boost accelerated superfractionated irradiation. Int J Radiat Oncol Biol Phys 32 (3): 635-41, 1995.

12 Licitra L, Grandi C, Guzzo M, et al.: Primary chemotherapy in resectable oral cavity squamous cell cancer: a randomized controlled trial. J Clin Oncol 21 (2): 327-33, 2003.

13 Stuschke M, Thames HD: Hyperfractionated radiotherapy of human tumors: overview of the randomized clinical trials. Int J Radiat Oncol Biol Phys 37 (2): 259-67, 1997.

14 Bachaud JM, David JM, Boussin G, et al.: Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial. Int J Radiat Oncol Biol Phys 20 (2): 243-6, 1991.

15 Merlano M, Corvo R, Margarino G, et al.: Combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck. The final report of a randomized trial. Cancer 67 (4): 915-21, 1991.

16 Pignon JP, Bourhis J, Domenge C, et al.: Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 355 (9208): 949-55, 2000.

17 Taylor SG 4th, Murthy AK, Vannetzel JM, et al.: Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol 12 (2): 385-95, 1994.

Stage IV Lip and Oral Cavity Cancer

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Randomized, prospective trials have yet to demonstrate a benefit in either disease-free or overall survival for patients receiving neoadjuvant chemotherapy.1 The use of isotretinoin (13-cis -retinoic acid) daily for 1 year to prevent development of second upper aerodigestive tract primaries is under clinical evaluation.2,

Advanced lesions of the lip

These lesions, including those involving bone, nerves, and lymph nodes, generally require a combination of surgery and radiation therapy. Such patients are appropriate candidates for clinical trials.

Standard treatment options :

  1. Surgery: A variety of surgical approaches can be used depending on the size and location of the lesion and the need for reconstruction. Treatment of both sides of the neck is indicated for selected patients.
  2. Radiation therapy: A variety of radiation therapy techniques can be used as dictated by the size and location of the lesion. Options include external-beam radiation therapy with or without brachytherapy.

Treatment options under clinical evaluation:

  • Superfractionated radiation therapy.3,

Advanced lesions of the anterior tongue

Standard treatment options:

  1. Selected patients may be treated with combined surgery (i.e., total glossectomy, sometimes requiring laryngectomy) that may be combined with postoperative radiation therapy.4,
  2. Patients with very-advanced lesions may be treated with palliative radiation therapy.

Advanced lesions of the buccal mucosa

Standard treatment options:

  1. Radical surgical resection alone.
  2. Radiation therapy alone.
  3. Surgical resection plus radiation therapy, generally postoperative.

Advanced lesions of the floor of mouth

Standard treatment options:

  1. A combination of surgery and radiation therapy, generally postoperative, is often used.
  2. For fixed nodes (≥5 cm) preoperative radiation therapy is often used.

Advanced lesions of the lower gingiva

Standard treatment options:

  • Far-advanced tumors with extensive destruction of the mandible and with nodal metastases are poorly controlled by surgery, radiation therapy, or a combination of both.

Advanced lesions of the retromolar trigone

Standard treatment options:

  • Surgical composite resection followed by postoperative radiation therapy.

Advanced lesions of the upper gingiva

Standard treatment options:

  • Lesions that are extensive and infiltrating generally require treatment by surgery in combination with radiation therapy.

Advanced lesions of the hard palate

Standard treatment options:

  • Lesions that are extensive and infiltrating generally require treatment by surgery in combination with radiation therapy.

Treatment options for management of lymph nodes: 5,

Patients with advanced lesions should have elective lymph node radiation therapy or node dissection. The risk of metastases to lymph nodes is increased by high-grade histology, large lesions, spread involving the wet mucosa of the lip or the buccal mucosa in patients with recurrent disease, and invasion of muscle (orbicularis oris).

Standard treatment options:

  1. Radiation therapy alone or neck dissection:
    • N1 (0-2 cm).
    • N2b or N3; all nodes <2 cm. (A combined surgical and radiation therapy approach should also be considered.)
  2. Radiation therapy and neck dissection:
    • N1 (2-3 cm), N2a, N3.
  3. Surgery followed by radiation therapy is indicated for the following:
    • Multiple positive nodes.
    • Contralateral subclinical metastases.
    • Invasion of tumor through the capsule of the lymph node.
    • N2b or N3 (one or more nodes in each neck, as appropriate, >2 cm).
  4. Radiation therapy prior to surgery:
    • Large fixed nodes.

Treatment options under clinical evaluation (all stage IV lesions):

  1. Chemotherapy has been combined with radiation therapy in patients who have locally advanced disease that is surgically unresectable.6,7,8,9,

    A meta-analysis of 63 randomized prospective trials published between 1965 and 1993 showed an 8% absolute survival advantage in the subset of patients receiving concomitant chemotherapy and radiation therapy.10,[Level of evidence: 2A] Patients receiving adjuvant or neoadjuvant chemotherapy had no survival advantage. Cost, quality of life, and morbidity data were not available; no standard regimen existed; and the trials were felt to be too heterogenous to provide definitive recommendations. The results of 18 ongoing trials may further clarify the role of concomitant chemotherapy and radiation therapy in the management of oral cavity cancer.

    The best chemotherapy to use and the appropriate way to integrate the 2 modalities is still unresolved.11,

    Similar approaches in the patient with resectable disease, in whom resection would lead to a major functional deficit, are also being explored in randomized trials but cannot be recommended at this time as standard.

  2. Clinical trials for advanced tumors evaluating the use of chemotherapy preoperatively, before radiation therapy, or as adjuvant therapy after surgery are appropriate.6,12,13,14,15,16,17,18,19 Information about ongoing clinical trials is available from the NCI Web site.
  3. Novel fractionation radiation therapy clinical trials are under clinical evaluation.20,


1 Mazeron JJ, Martin M, Brun B, et al.: Induction chemotherapy in head and neck cancer: results of a phase III trial. Head Neck 14 (2): 85-91, 1992 Mar-Apr.

2 Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 323 (12): 795-801, 1990.

3 Johnson CR, Khandelwal SR, Schmidt-Ullrich RK, et al.: The influence of quantitative tumor volume measurements on local control in advanced head and neck cancer using concomitant boost accelerated superfractionated irradiation. Int J Radiat Oncol Biol Phys 32 (3): 635-41, 1995.

4 Franceschi D, Gupta R, Spiro RH, et al.: Improved survival in the treatment of squamous carcinoma of the oral tongue. Am J Surg 166 (4): 360-5, 1993.

5 Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott-Raven, 1999.

6 Al-Sarraf M, Pajak TF, Marcial VA, et al.: Concurrent radiotherapy and chemotherapy with cisplatin in inoperable squamous cell carcinoma of the head and neck. An RTOG Study. Cancer 59 (2): 259-65, 1987.

7 Bachaud JM, David JM, Boussin G, et al.: Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial. Int J Radiat Oncol Biol Phys 20 (2): 243-6, 1991.

8 Merlano M, Corvo R, Margarino G, et al.: Combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck. The final report of a randomized trial. Cancer 67 (4): 915-21, 1991.

9 Merlano M, Benasso M, Corvò R, et al.: Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck. J Natl Cancer Inst 88 (9): 583-9, 1996.

10 Pignon JP, Bourhis J, Domenge C, et al.: Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 355 (9208): 949-55, 2000.

11 Taylor SG 4th, Murthy AK, Vannetzel JM, et al.: Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol 12 (2): 385-95, 1994.

12 Al-Kourainy K, Kish J, Ensley J, et al.: Achievement of superior survival for histologically negative versus histologically positive clinically complete responders to cisplatin combination in patients with locally advanced head and neck cancer. Cancer 59 (2): 233-8, 1987.

13 Adjuvant chemotherapy for advanced head and neck squamous carcinoma. Final report of the Head and Neck Contracts Program. Cancer 60 (3): 301-11, 1987.

14 Toohill RJ, Duncavage JA, Grossmam TW, et al.: The effects of delay in standard treatment due to induction chemotherapy in two randomized prospective studies. Laryngoscope 97 (4): 407-12, 1987.

15 Ensley J, Crissman J, Kish J, et al.: The impact of conventional morphologic analysis on response rates and survival in patients with advanced head and neck cancers treated initially with cisplatin-containing combination chemotherapy. Cancer 57 (4): 711-7, 1986.

16 Fu KK, Phillips TL, Silverberg IJ, et al.: Combined radiotherapy and chemotherapy with bleomycin and methotrexate for advanced inoperable head and neck cancer: update of a Northern California Oncology Group randomized trial. J Clin Oncol 5 (9): 1410-8, 1987.

17 Ryan RF, Krementz ET, Truesdale GL: Salvage of stage IV intraoral squamous cell carcinomas with preoperative 5-fluorouracil. Cancer 57 (4): 699-705, 1986.

18 Ervin TJ, Clark JR, Weichselbaum RR, et al.: An analysis of induction and adjuvant chemotherapy in the multidisciplinary treatment of squamous-cell carcinoma of the head and neck. J Clin Oncol 5 (1): 10-20, 1987.

19 Browman GP, Cripps C, Hodson DI, et al.: Placebo-controlled randomized trial of infusional fluorouracil during standard radiotherapy in locally advanced head and neck cancer. J Clin Oncol 12 (12): 2648-53, 1994.

20 Stuschke M, Thames HD: Hyperfractionated radiotherapy of human tumors: overview of the randomized clinical trials. Int J Radiat Oncol Biol Phys 37 (2): 259-67, 1997.

Recurrent Lip and Oral Cavity Cancer

For lesions of the lip, anterior tongue, buccal mucosa, floor of mouth, retromolar trigone, upper gingiva, and hard palate, treatment will be dictated by the location and size of the recurrent lesion as well as prior treatment.1,2,

Standard treatment options:

  1. If radiation therapy was used initially, surgery is the preferred treatment.3,
  2. If surgery was used to treat the lesion initially, surgery,3 radiation therapy, or a combination of these may be considered.
  3. Although chemotherapy has been shown to induce responses, no increase in survival has been demonstrated.4,

Treatment options under clinical evaluation:

  • Because surgical salvage after primary treatment by radiation therapy and radiation therapy after primary surgery give poor results, clinical trials evaluating new chemotherapy drugs, chemotherapy and reirradiation, or hyperthermia should be considered.5,6 Information about ongoing clinical trials is available from the NCI Web site.


1 Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott-Raven, 1999.

2 Vikram B, Strong EW, Shah JP, et al.: Intraoperative radiotherapy in patients with recurrent head and neck cancer. Am J Surg 150 (4): 485-7, 1985.

3 Wong LY, Wei WI, Lam LK, et al.: Salvage of recurrent head and neck squamous cell carcinoma after primary curative surgery. Head Neck 25 (11): 953-9, 2003.

4 Jacobs C, Lyman G, Velez-García E, et al.: A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol 10 (2): 257-63, 1992.

5 Hong WK, Bromer R: Chemotherapy in head and neck cancer. N Engl J Med 308 (2): 75-9, 1983.

6 Vokes EE, Athanasiadis I: Chemotherapy of squamous cell carcinoma of head and neck: the future is now. Ann Oncol 7 (1): 15-29, 1996.

Changes to This Summary (06/17/2005)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Stage III Lip and Oral Cavity Cancer

Added Licitra et al. as reference 12.

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2005-06-17







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