Lip And Oral Cavity Cancer Treatment (Adult) (PDQ®): Treatment - Health Professional Information [NCI]

General Information About Lip and Oral Cavity Cancer

Anatomy

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.

Histopathology

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.

Precancerous lesions of the oropharynx include leukoplakia, erythroplakia, and mixed erythroleukoplakia.[1] Leukoplakia, the most common of the three conditions, is defined by the World Health Organization as "a white patch or plaque that cannot be characterized clinically or pathologically as any other disease."[2] The diagnosis of leukoplakia is one of exclusion; conditions such as candidiasis, lichen planus, leukoedema, and others must be ruled out before a diagnosis of leukoplakia can be made.[1]

The prevalence of leukoplakia in the United States is decreasing as a result of reduced tobacco consumption.[3] Although erythroplakia is not as common as leukoplakia, it is much more likely to be associated with dysplasia or carcinoma.[1,4]

Prognostic Factors

Early cancers (stage I and stage II) of the lip and oral cavity are highly curable by surgery or radiation therapy. The choice of treatment is dictated by the anticipated functional and cosmetic results of treatment and by the availability of a surgeon or radiation oncologist with the required expertise.[5,6,7] A positive surgical margin or a tumor depth of more than 5 mm significantly increases the risk of local recurrence.[8,9] The risk of occult nodal metastases increases based on depth of invasion of the primary tumor. Depth of invasion holds prognostic significance and was included in tumor staging definitions in the American Joint Committee on Cancer (AJCC) 8th edition staging classification.[10,11] Extranodal extension in a lymph node is a significant adverse prognostic factor and was incorporated into the 8th edition AJCC staging system.[12,13]

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. Most patients with stage III or stage IV tumors are candidates for treatment by a combination of surgery and radiation therapy. The exception is patients with small T3 lesions and no regional lymph node and no distant metastases or who have no lymph nodes larger than 2 cm in diameter, for whom treatment by radiation therapy alone or surgery alone might be appropriate.[6] Furthermore, because local recurrence and/or distant metastases are common in this group of patients, clinical trials can be considered. Such trials evaluate the potential role of radiation modifiers or combination chemotherapy combined with surgery and/or radiation therapy.

Survival

Patients with head and neck cancers have an increased chance of developing a second primary tumor of the upper aerodigestive tract.[14,15] A study has shown that daily treatment with moderate doses of isotretinoin for 1 year can significantly reduce the incidence of second tumors. However, no survival advantage has been demonstrated, in part due to recurrence and death from the primary malignancy. An additional trial showed no benefit of retinyl palmitate or retinyl palmitate plus beta-carotene when compared with isotretinoin alone.[16][Level of evidence B1]

The cure rates of cancers of the lip and oral cavity depend 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 high as 100%. Local control rates as high 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.[17]

Moderately advanced and advanced cancers of the lip also can be controlled effectively by surgery, radiation therapy, or both. 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 as high as 90%. Such lesions of the hard palate, upper gingiva, and buccal mucosa have a local control rate of up to 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 high as 70% and 65%, respectively.[17,18]

References:

1. Neville BW, Day TA: Oral cancer and precancerous lesions. CA Cancer J Clin 52 (4): 195-215, 2002 Jul-Aug.
2. Kramer IR, Lucas RB, Pindborg JJ, et al.: Definition of leukoplakia and related lesions: an aid to studies on oral precancer. Oral Surg Oral Med Oral Pathol 46 (4): 518-39, 1978.
3. Scheifele C, Reichart PA, Dietrich T: Low prevalence of oral leukoplakia in a representative sample of the US population. Oral Oncol 39 (6): 619-25, 2003.
4. Shafer WG, Waldron CA: Erythroplakia of the oral cavity. Cancer 36 (3): 1021-8, 1975.
5. Cummings CW, Fredrickson JM, Harker LA, et al.: Otolaryngology - Head and Neck Surgery. Mosby-Year Book, Inc., 1998.
6. Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. 3rd ed. Lippincott, William & Wilkins, 2009.
7. Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. Wiley-Liss, 1997.
8. 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.
9. 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.
10. Sparano A, Weinstein G, Chalian A, et al.: Multivariate predictors of occult neck metastasis in early oral tongue cancer. Otolaryngol Head Neck Surg 131 (4): 472-6, 2004.
11. D'Cruz AK, Vaish R, Kapre N, et al.: Elective versus Therapeutic Neck Dissection in Node-Negative Oral Cancer. N Engl J Med 373 (6): 521-9, 2015.
12. Cooper JS, Pajak TF, Forastiere AA, et al.: Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350 (19): 1937-44, 2004.
13. Bernier J, Cooper JS, Pajak TF, et al.: Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 27 (10): 843-50, 2005.
14. Day GL, Blot WJ: Second primary tumors in patients with oral cancer. Cancer 70 (1): 14-9, 1992.
15. 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.
16. Papadimitrakopoulou VA, Lee JJ, William WN, et al.: Randomized trial of 13-cis retinoic acid compared with retinyl palmitate with or without beta-carotene in oral premalignancy. J Clin Oncol 27 (4): 599-604, 2009.
17. 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.
18. 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.