				Using the search form

If you prefer to view this article in PDF form, click here.

Oral cancer: How to find this hidden killer in 2 minutes

A brief, simple assessment can save lives, possibly because you may be the only provider to thoroughly examine the inside of the patient’s mouth.

Denise Rizzolo, PA-C, MSPA; Christopher Hanifin, PA-C, MSPA; Thomas A. Chiodo, DDS

Denise Rizzolo is a faculty member in the PA program at Seton Hall University and practices at the Care Station, Springfield, New Jersey. Christopher Hanifin is a faculty member in the PA program at Seton Hall University and works in the Department of Emergency Medicine at Morristown Memorial Hospital, Morristown, New Jersey. Thomas Chiodo is an oral maxillofacial surgeon in Somerville, New Jersey. The authors have indicated no relationships to disclose relating to the content of this article.

In April 1923, oral cancer was diagnosed in a world-renowned physician. He had started smoking cigars at age 24 years and smoked as many as 20 cigars a day. At age 67, he sought treatment for an oral lesion that was diagnosed as malignant. Despite the best efforts of his surgeons over the course of 30 operations, the cancer progressed.¹ At age 83, the patient could no longer endure the pain and asked for assistance in ending his life with a morphine overdose.² Today, Sigmund Freud would have been treated differently. But despite the advances in the diagnosis and treatment of oral cancer since Freud’s time, the survival rate has not improved significantly.³

EPIDEMIOLOGY AND ETIOLOGY

Oral cancer is estimated to be the sixth most common cancer in the world.⁴ According to American Cancer Society estimates, about 30,990 new cases of oropharyngeal cancer were diagnosed in the United States in 2006, and approximately 7,430 people died from oral cancer.⁵ More than 90% of cancers in the mouth are squamous cell carcinomas, most frequently of the tongue.³ Many primary care clinicians expect that their patients receive a complete oral examination from their dentists. Large segments of the population, however, lack dental insurance or do not regularly visit a dentist. Furthermore, in a study conducted in 2005, Cruz and colleagues found that almost 20% of dentists and 30% of dental hygienists do not routinely examine patients for oral cancer.⁶ Primary care clinicians must be able to recognize oral lesions and make appropriate recommendations for follow-up.

A thorough history is critical in identifying persons at risk for oral cancer. The most well-established risk factors are tobacco and alcohol use.⁷ People who smoke cigarettes are 4 times more likely to develop oral cancer than are nonsmokers. Those who smoke have a greater risk of oral cancer than those who use smokeless tobacco.

People who consume alcohol are 3 times more likely to develop oral cancer than nondrinkers.⁸ The type of alcohol consumed is also significant: drinking hard alcohol is associated with a greater risk than drinking beer or wine.⁹ When alcohol is combined with tobacco use, the incidence of cancer is markedly increased.¹⁰

Other habits may affect the risk of oral cancer. Caffeine is one of the most widely consumed “drugs” in the world. Coffee has been suspected as a carcinogen by some researchers; however, one study actually indicated that coffee might have a protective effect against oral cancer.¹¹ The study also found no significant adverse or protective effects associated with decaffeinated coffee or tea.

A person’s cultural practices may increase risk, as well. Consumption of maté, a South American tea, increases the risk of both oral and esophageal squamous cell carcinoma.¹² Other authors studying maté note that beverage temperature also may be significant; higher incidence rates were associated with consumption of increasingly hot beverages.¹³ Throughout South Asia and the Pacific Rim, approximately 200 million people chew betel quid, a substance composed of the nut of the areca palm, a betel pepper leaf, and quicklime (calcium hydroxide). Use of betel has been associated with oral squamous cell carcinoma.¹⁴

Systemic diseases such as erosive lichen planus are associated with oral cancer. In cases of longstanding lichen planus, instances of malignant transformation within the mucosal lesions were reported.¹⁵ Any process that weakens the immune system may also promote malignant transformation because of decreased immune surveillance. Epstein-Barr virus and human papillomavirus are suspected of possibly contributing to the development of oral cancer.^16,17

An occupational history may uncover additional risk factors. People who have industrial jobs typically have a higher risk of oral cancer.^18,19 Exposure to toxins such as metal dust, solvents, paints, lacquers, and varnishes is likely what increases the risk. The clinician should, therefore, inquire about any toxic materials patients may encounter through their job, hobbies, or military service.

Education is critical for those patients whose lifestyle places them at risk for oral cancer. Patients who use tobacco or alcohol may be well aware that they are increasing their risks of lung or liver disease, but the majority do not consider themselves to be at increased risk for oral cancer.²⁰

THE ORAL EXAMINATION

Although the United States Preventive Services Task Force has concluded that evidence is insufficient to recommend for or against routine screening for oral cancer, the best hope for early detection, while the cancer is still treatable, is by screening.²¹ The screening examination takes less than 2 minutes to perform and should be a routine part of the physical examination. Patients with significant risk factors, especially those who use tobacco and alcohol, should be carefully screened. Many clinicians routinely perform a cursory examination of the oral cavity; however, the tongue is usually depressed and the lateral surfaces of the tongue and the floor of the mouth are not examined. This can be problematic because these are two common places where oral cancer can develop.

The two key components of the oral examination are inspection and palpation of both external and intraoral structures. The examination begins with an inspection of the head, face, and neck looking for coloration, swelling, and symmetry. Since most head and neck cancers are unilateral, any asymmetry is investigated.

External examination Palpate the head thoroughly, including the temporal muscles, temporomandibular joints, masseter muscles, and bony mandible. Next, palpate the neck, including the parotid and submandibular glands, the lymph nodes, and the neck musculature.

Internal examination A careful search is made for any areas that vary from the normal pink color of healthy mucosa (see Figure 1). Almost all oral squamous cell carcinomas are preceded by readily visible changes in the oral mucosa that most commonly manifest as red or white patches.²²

Retract the upper lip superiorly, and examine the mucosa and gingiva (A). Manipulate the lip with the thumb and index finger, feeling for any submucosal lesions (B). Examine the buccal mucosa and posterior gingiva one side at a time by retracting the commissure of the lips laterally and then superiorly (C). Retract the lower lip and examine the mucosa, vestibule, and anterior gingiva (D). Next, examine the entire hard palate (E). Depress the tongue with a tongue blade while the patient says “ahhh” (F). (This maneuver elevates the soft palate and allows a better view of the tonsillar area.) Ask the patient to raise his or her tongue to the roof of the mouth and examine the ventral surface of the tongue and floor of the mouth (G). Finally, extend the tongue out of the mouth and hold it with a 2 3 2 gauze square and examine the lateral borders of the tongue (H).

Palpation of the oral cavity also is important. All surfaces of the buccal mucosa, floor of mouth, and tongue should be palpated. Proper palpation is accomplished using a bimanual technique that sandwiches the target structures. Better tactile sensation of the soft, mobile structures of the face and oral cavity is achieved using this method.

COMMON ORAL LESIONS

Two common premalignant lesions of the oral cavity are leukoplakia and erythroplakia. Prompt treatment of these dysplastic lesions may diminish the risk of disease progression.

Leukoplakia generally manifests as asymptomatic, white, macular lesions that do not wipe off (see Figure 2). The lesions may be isolated or diffuse in nature and occur most commonly on the tongue, the floor of the mouth, and the buccal mucosa.

Erythroplakia manifests as a patch of macular or ulcerated red lesions (see Figure 3). The lesions appear in the same locations as leukoplakia and can be asymptomatic or mildly painful. The incidences of dysplasia and carcinoma are higher in red lesions than in white lesions. Biopsy is indicated for any abnormality present for more than 14 days without an obvious etiology, such as trauma.

Most oral cancer lesions are painless, but some are accompanied by pain.²³ Pain unfortunately often indicates the cancer has invaded the adjacent structures, making a cure unlikely. Any patient presenting with orofacial pain requires a thorough examination.

Squamous cell carcinoma can manifest on any mucosal surface but most commonly appears on the lateral and ventral tongue (75%), followed by the floor of the mouth (15%-20%). About 10% of carcinomas are found on the buccal mucosa, 10% on the gingival surfaces, 10% to 15% on the soft palate, and 5% on the hard palate.²⁴

Carcinoma of the tongue most commonly appears on the lateral border of the tongue in the area of the lingueal tonsils (see Figure 4). The left side is a more common site than the right, possibly because right-handed smokers would aim the smoke stream toward the left.²⁵ The posterior portion of the tongue also is a common site. Carcinoma on the posterior portion of the tongue often crosses the midline and is more likely to metastasize to the lymph nodes and manifest as a bilateral neck mass. Carcinoma of the tongue can be exophytic or ulcerated, and the color may be red, white, or both.

The differential diagnosis includes oral tuberculosis, systemic fungal diseases, trauma, and primary syphilis. If a large neck mass is present, cervical tuberculosis adenitis, cat-scratch disease, brachial cysts, non-Hodgkin’s lymphoma, and Hodgkin’s disease should be considered.²⁵

Carcinoma of the floor of the mouth manifests as a red-white patch or ulcer (see Figure 5). Induration indicates the lesion has infiltrated the underlying tissue. Patients may present with bilateral regional neck metastasis because the tissues along the floor of the mouth are thin. The differential diagnosis includes traumatic ulcers, syphilis, premalignant dysplasias, and verrucous carcinomas.²⁵

Carcinoma of the buccal mucosa manifests as a red-white patch that is usually asymptomatic or may appear exophytic. If carcinoma infiltrates the underlying tissues, the cheek may become indurated. The patient’s ability to open his or her jaw will be limited if the masseter or temporalis muscles are affected. The most common differential diagnosis is erosive lichen planus, which is painful and usually occurs on multiple sites within the oral cavity.²⁵

Carcinoma of the gingiva manifests as a red-white thickening of the marginal and interdental gingiva without ulcerations (see Figure 6). The disease is slow-growing and has a low likelihood of metastasis. The most common condition it mimics is periodontitis. Other differential diagnoses include lichen planus and pemphigoid.²⁵

Carcinoma of the hard and soft palate is a common finding in patients who practice reverse smoking²⁵ (see Figure 7). In reverse smoking, most commonly practiced in Asian cultures, the smoker places the lit end of the cigarette inside the oral cavity when inhaling. On the hard palate, the lesions appear as ulcerated red-white patches and frequently extend into the alveolar ridge. Carcinoma of the soft palate appears as nonulcerated red-white patches, and may be indurated. When developing a differential diagnosis, the clinician should consider three additional conditions: extranodal non-Hodgkin’s lymphoma, necrotizing carcinoma, and primary carcinoma arising in the maxillary sinus. Additional possibilities include systemic fungal diseases and syphilis.²⁵

DIAGNOSIS AND STAGING

A clinical diagnosis is made by examination, staging, and biopsy. A valuable diagnostic aid is to stain the lesion with 1% toluidine blue 0. When applied to the mucosa, toluidine blue 0 will stain malignant epithelia of the mucous membranes, but normal tissue does not retain the dye. Toluidine blue 0 serves only as a diagnostic aid; the dye does not establish a definitive diagnosis.²⁶

Clinical staging of suspicious lesions should be attempted before biopsy. The biopsy itself may distort the lesion or cause inflammation of regional lymph nodes, which can confuse later staging.²⁵ Clinical staging is based on the TNM classification system (see Table 1).

A biopsy should be obtained as soon as practical because many patients fear the potential diagnosis of cancer and will not adhere to follow-up.²⁵ Once the diagnosis is confirmed, CT of the head, neck, and chest is used to identify the extent of tumor invasion, lymph node involvement, and any distant metastases.³ Positron emission tomography (PET) has excellent sensitivity for detecting possible malignancies, which allows for earlier detection and staging. However, PET lacks the resolution necessary to determine the precise anatomic location of the lesion.^23,27 PET-CT is a new imaging technology that combines the resolution of CT with the sensitivity of PET. It holds great promise as an improved imaging study for the diagnosis and treatment of oral carcinoma.

TREATMENT AND PROGNOSIS

A multidisciplinary approach should be used for managing patients with invasive oral cancer. Consultations may include oncology, maxillofacial surgery, otolaryngology, and plastic surgery. Other ancillary clinicians who may be included in the patient’s treatment are speech pathologists and nutrition counselors.³

Treatment depends on tumor size, location of tumor, lymph node involvement, presence or absence of metastasis, and patient preference.³ Primary treatment modalities are surgery, radiation, chemotherapy, or combination therapy. Selective or radical neck dissection of the associated lymphatic chain may be performed at the primary cancer site because these lesions commonly metastasize to the associated cervical lymph nodes. Depending on the cancer site, 5-year survival rates range from 15% to 90%.²⁵

In addition to traditional prognostic markers such as tumor stage, researchers have found other factors that are significant to oral cancer prognosis. Patients with a strong social support system have demonstrated improved 5-year survival rates over those who do not practice a religion and those who are single, divorced, or widowed.²⁸

As is the case with all cancer patients, maintaining adequate nutrition is critical. A good diet affords the body the best chance of coping with the stress of surgery and chemotherapy or radiation therapy.²⁹ Finally, a significant number of patients with oral cancer continue to use tobacco and alcohol after diagnosis. All patients with oral cancer must be counseled to avoid using alcohol and tobacco.

CONCLUSION

The key to a good outcome is early diagnosis and treatment. Primary care clinicians must ask patients about risk factors, particularly smoking and alcohol use, at every patient encounter. A complete examination of the oral cavity should be a part of the routine physical examination for all patients aged 40 years and older. Clinicians must become proficient in identifying premalignant and malignant lesions in the early stages of development, when prognosis and survival rates are the highest. Screening for breast, cervical, and colon cancers has had a positive effect on outcomes; the time has come to include oral cancer in routine screening practices as well.

REFERENCES

	1.	Schur M. Freud: Living and Dying. Madison, CT: International Universities Press; 1972.
	2.	Lazaridis N. Sigmund Freud’s oral cancer. Br J Oral Maxillofac Surg. 2003;41(2):78-83.
	3.	Neville BW, Day TA. Oral cancer and precancerous lesions. CA Cancer J Clin. 2002;52(4):195-215.
	4.	Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of twenty-five major cancers in 1990. Int J Cancer. 1999;80(6):827-841.
	5.	Detailed guide: oral cavity and oropharyngeal cancer. What are the key statistics about oral cavity and oropharyngeal cancer? American Cancer Society Web site. http://www.cancer. org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_statistics_for_oral_cavity_and_ oropharyngeal_cancer_60.asp?sitearea. Accessed September 12, 2007.
	6.	Cruz GD, Ostroff JS, Kumar JV, Gajendra S. Preventing and detecting oral cancer. Oral health care providers’ readiness to provide health behavior counseling and oral cancer examinations. J Am Dent Assoc. 2005;136(5):594-601.
	7.	Wynder EL, Bross IJ, Feldman RM. A study of etiologic factors in cancer of the mouth. Cancer. 1957;10(6):1300-1323.
	8.	Bagnardi V, Blangiardo M, LaVecchia C, Corrao G. Alcohol consumption and the risk of cancer. Alcohol Res Health. 2001;25(4):263-270.
	9.	Schlect NF, Pintos J, Kowalski LP, Franco EL. Effect of type of alcoholic beverage on the risk of upper aerodigestive tract cancers in Brazil. Cancer Causes Control. 2001;12(7):579-581.
	10.	Castellsagué X, Quintana MJ, Martinez MC, et al. The role of type of tobacco and type of alcoholic beverage in oral carcinogenesis. Int J Cancer. 2004;108(5):741-749.
	11.	Tavani A, Bertuzzi M, Talamini R, et al. Coffee and tea intake and risk of oral, pharyngeal and esophageal cancer. Oral Oncol. 2003;39(7):695-700.
	12.	Goldenberg D. Maté: a risk factor for oral and oropharyngeal cancer. Oral Oncol. 2002;38(7):646-649.
	13.	Castellsagué X, Muñoz N, DeStefani E, et al. Influence of mate drinking, hot beverages and diet on esophageal cancer risk in South America. Int J Cancer. 2000;88(4):658-664.
	14.	Norton, SA. Betel: consumption and consequences. J Am Acad Dermatol. 1998;38(1):81-88.
	15.	Fatahzadeh M, Rinaggio J, Chiodo T. Squamous cell carcinoma arising in an oral lichenoid lesion. J Am Dent Assoc. 2004;135(6):754-759.
	16.	Tachezy R, Klozar J, Saláková M, et al. HPV and other risk factors of oral cavity/oropharyngeal cancer in the Czech Republic. Oral Dis. 2005;11(3):181-185.
	17.	Sand LP, Jalouli J, Larsson PA, Hirsch JM. Prevalence of Epstein-Barr virus in oral squamous cell carcinoma, oral lichen planus, and normal oral mucosa. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002;93(5):586-592.
	18.	Tisch M, Maier H, Keller A. Oral cancer in machine workers. Poster presented at: Annual Meeting of the American Academy of Otolaryngology–Head and Neck Surgery Foundation; September 26-29, 1999; New Orleans, LA. Abstract 95.
	19.	Andreotti M, Rodrigues AN, Cardoso LM, et al. [Occupational status and cancer of the oral cavity and oropharynx]. Cad Saude Publica. 2006;22(3):543-552.
	20.	Humphris GM, Freeman R, Clarke HM. Risk perception of oral cancers in smokers attending primary care: a randomised controlled trial. Oral Oncol. 2004;40(9):916-924.
	21.	US Preventive Services Task Force, US Department of Health and Human Services. Screening for Oral Cancer Recommendation Statement. Rockville, MD: Agency for Healthcare Research and Quality; 2004. AHRQ publication 05-0564-A.
	22.	Mignona MD, Fedele S, Lo Russo L, et al. Costs and effectiveness in the care of patients with oral and pharyngeal cancer: analysis of a paradox. Eur J Cancer Prev. 2002;11(3):205-208.
	23.	Juweid ME, Cheson BD. Positron-emission tomography and assessment of cancer therapy. N Engl J Med. 2006;354(5):496-507.
	24.	Cuffari L, Tesseroli de Siquiera JT, Nemr K, Rapaport A. Pain complaint as the first symptom of oral cancer: a descriptive study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102(1):56-61.
	25.	Marx RE, Stern D. Mucosal squamous cell carcinomas. In: Marx, RE, Stern D. Oral and Maxillofacial Pathology A Rational for Diagnosis and Treatment. Carol Stream, IL: Quintessence Publishing Co, Inc; 2003:326-346.
	26.	Warnakulasuriya KA, Johnson NW. Sensitivity and specificity of OraScan toluidine blue mouthrinse in the detection of oral cancer and precancer. J Oral Pathol Med. 1996;25(3):97-103.
	27.	Tamara L, Velez I, Tamara C. Positron emission tomography: a promising diagnostic modality for head and neck pathology. J Oral Maxillofac Surg. 2006;64(8):1272-1277.
	28.	Wong YK, Tsai WC, Lin JC, et al. Socio-demographic factors in the prognosis of oral cancer patients. Oral Oncol. 2006;42(9):893-906.
	29.	Liu SA, Tsai WC, Wong YK et al. Nutritional factors and survival of patients with oral cancer. Head Neck. 2006;28(11):998-1007.