16.  Screening for Oral Cancer



RECOMMENDATION



There is insufficient evidence to recommend for or against routine

screening of asymptomatic persons for oral cancer by primary care

clinicians. All patients should be counseled to discontinue the use of all

forms of tobacco (see Chapter 54) and to limit consumption of alcohol

(see Chapter 52). Clinicians should remain alert to signs and symptoms of

oral cancer and premalignancy in persons who use tobacco or regularly use

alcohol.



Burden of Suffering



The term "oral cancer" includes a diverse group of tumors arising from the

oral cavity. Usually included are cancers of the lip, tongue, pharynx, and

oral cavity. The annual incidence of oral cancer in the U.S. is about

11/100,000 population, with a male/female ratio greater than 2:1.1 Oral

cancer is responsible for 2% of all cancer deaths in the U.S., and it is

projected to account for over 28,000 new cases and about 8,400 deaths in

1995.2



Fifty-three percent of oral cancers have spread to regional or distant

structures at the time of diagnosis.1 Overall 5-year survival is 52%, but

it ranges from 79% for localized disease to 19% if distant metastases are

present.1 The natural history of each type of cancer can be quite different.

Cancer of the lip accounts for 11% of new cases of oral cancer but only 1%

of deaths. In contrast, cancer of the pharynx accounts for 31% of new

cases of oral cancer but 50% of deaths.1 The median age at diagnosis of

oral cancers is 64 years, and 95% occur in persons over age 40. About half

of all oropharyngeal cancers and the majority of deaths from this disease

occur in persons over age 65.1



Use of tobacco in all forms and, to a lesser extent, alcohol abuse are the

major risk factors for the development of oral cancer.3 The risk of oral

cancer is increased 6-28 times in current smokers,4 and the effects of

tobacco and alcohol account for 90% of oral cancer in the U.S.5 In parts of

India and Asia where chewing tobacco or betel nut is very common, the

incidence of oral cancer is 3 times higher than in the U.S.5 In several

areas of India, oral cancer accounts for 40% of all female cancer deaths.5

Other risk factors for oral cancer include occupational exposures, solar

radiation (for cancer of the lip), and the presence of premalignant lesions

such as leukoplakia or erythroplakia.3 Depending on the degree of

histologic 



abnormality, up to 18% of cases of leukoplakia may develop into invasive

cancers over long-term follow-up.5 Patients infected with human

immunodeficiency virus are at increased risk of oral cancers, most

commonly 



Kaposi's sarcoma and non-Hodgkin's lymphoma.6



Accuracy of Screening Tests



The principal screening test for oropharyngeal cancer in asymptomatic

persons is inspection and palpation of the oral cavity. Studies indicate

that many oral cancers occur on the floor of the mouth, the ventral and

lateral regions of the tongue, and the soft palate, anatomic sites that may

be inaccessible to routine visual inspection.7 The recommended

examination technique involves a careful visual examination of the oral

cavity and extraoral areas using a dental mirror, retracting the tongue

with a gauze pad to visualize hard-to-see areas. It also includes digital

palpation with a gloved hand for masses. Complete descriptions of the

recommended techniques have been published.8 There is little information,

however, on the sensitivity of this procedure in detecting oral cancer or

on the frequency of false-positive results when a lesion is found. The

abbreviated oral inspection that is more typical of the routine physical

examination is also of unknown accuracy and predictive value. Studies in

India and Sri Lanka have shown that nonphysician basic health care

workers, given a short course on screening for oral cancer, can identify

oral cancers and their precursors.9,10 Mehta found a 59% sensitivity and

98% specificity for lesions appropriately referred to dentists by the basic

health care workers.9 No outcome data were reported in these studies, and

it is unclear how these findings relate to the very different, lower

prevalence population of the United States.



Some studies suggest that dentists are more effective than are physicians

in routinely performing a complete mouth examination and detecting

early-stage oral cancer.11 Older Americans, the population at greatest

risk for oral cancer, visit the dentist infrequently, however; physician

visits are much more frequent in older persons.12 No studies of the

sensitivity and specificity of screening for oral cancer by dentists have

been reported.



Alternative screening tests for oral cancer have been proposed, such as

tolonium chloride rinses to stain suspicious lesions,13,14 but further

research is needed to evaluate the accuracy and acceptability of these

techniques before routine use in the general population can be considered.



Effectiveness of Early Detection



No controlled trials of screening for oral cancer that include data on

clinical outcomes have been reported. There is consistent evidence that

persons with early-stage oral cancer have a better prognosis than those

diagnosed with more advanced disease.1,2 Because of the possible effects

of lead-time and length bias, however, these observational data are not

sufficient to prove that screening and earlier detection improve the

prognosis in patients with oral cancer. Some authors have questioned the

effectiveness of early detection in improving prognosis.15 Prospective

trials of screening for oral cancer, although difficult and expensive to

conduct in the general population, might be feasible in high-risk

populations in which the incidence of oral cancer is substantially greater.



Several studies have examined treatment of oral leukoplakia, a form of

premalignancy, as a means of preventing oral cancer. Primary treatment of

oral leukoplakia and prevention of second primary lesions in patients with

treated oral cancer have been studied in several randomized, placebo-

controlled chemoprevention trials of high-dose isotretinoin (13-cis-

retinoic acid).16-18 These studies demonstrated that isotretinoin was

effective in promoting remission of leukoplakia and preventing the

occurrence of second primary oral cancers.17 Leukoplakia relapsed in a

majority of cases within 3-6 months after discontinuation of therapy,

however, and the rate of toxicity of treatment was high (mild to moderate

side effects in up to 79% of patients). A trial of alternate maintenance

therapies after isotretinoin induction for leukoplakia suggested that low-

dose isotretinoin was more effective in maintaining remissions than b-

carotene and caused fewer side effects than high-dose therapy: 12% of

participants experienced severe toxicity and 42% had moderate toxicity

from low-dose isotretinoin, including dry skin, cheilitis, and

conjunctivitis.18



Uncontrolled trials using b-carotene demonstrated variable reductions (up

to 71%) in the occurrence of oral leukoplakia and mucosal dysplasia.19-21

In a randomized trial, however, the majority of patients with leukoplakia

progressed during b-carotene treatment.18 Although side effects of b-

carotene are minimal, older male smokers who took b-carotene for 5-8

years experienced slightly higher rates of lung cancer and overall

mortality in a recently completed trial in Finland.22 Research is currently

in progress on alternative agents (e.g., vitamin E) and combinations of

therapies.23



Recommendations of Other Groups



The American Cancer Society recommends a cancer checkup that includes

oral examination every 3 years for persons over age 20 and annually for

those over age 40.24 The Canadian Task Force on the Periodic Health

Examination concluded that there was insufficient evidence to include or

exclude screening for oral cancer in the periodic health examination of

persons in the general population, but suggested that annual oral

examination by a physician or dentist should be considered for persons

over 60 with risk factors for oral cancer (e.g., smokers and regular

drinkers).25 Although the National Institutes of Health no longer issue

specific clinical guidelines regarding screening for oral cancer, both the

National Cancer Institute and the National Institute of Dental Research

support efforts to promote the early detection of oral cancers during

routine dental examinations.8,26



Discussion



Primary prevention strategies, such as counseling patients regarding the

use of tobacco and alcohol, may have a greater impact on the morbidity

and mortality associated with oral cancer than measures aimed at early

detection. There is good evidence that tobacco use and excessive

consumption of alcohol are both independent and synergistic risk factors

for oral cancer.3 Over 90% of oropharyngeal cancer deaths are associated

with smoking.5 In addition to smoking and alcohol, oral cancer is also

associated with the use of snuff and chewing tobacco.27



Oral cancer is a relatively uncommon cancer in the United States. Even

among high-risk groups such as smokers, oral cancer accounts for a

relatively small proportion (<2%) of all deaths.4 Available screening tests

for oral cancer are limited to the physical examination of the mouth, a

test of undetermined sensitivity, specificity, and positive predictive

value. Despite the strong association between stage at diagnosis and

survival, there are few controlled data to determine whether routine

screening in the primary care setting leads to earlier diagnosis or reduced

mortality from oral cancer. Given the significant morbidity and mortality

associated with advanced oral cancer and its treatment, clinicians may

wish to include careful examinations for oral cancer in asymptomatic

persons at significantly increased risk for the disease (see Clinical

Intervention); direct evidence of a benefit of screening in any group,

however, is lacking. It is also appropriate to refer patients for regular

visits to a dentist, for whom complete examination of the oral cavity is

often more feasible (see Chapter 61).



CLINICAL INTERVENTION



There is insufficient evidence to recommend for or against routine

screening of asymptomatic persons for oral cancer by primary care

clinicians ("C" recommendation). Although direct evidence of a benefit is

lacking, clinicians may wish to include an examination for cancerous and

precancerous lesions of the oral cavity in the periodic health examination

of persons who chew or smoke tobacco (or did so previously), older

persons who drink regularly, and anyone with suspicious symptoms or

lesions detected through self-examination. All patients, especially those

at increased risk, should be advised to receive a complete dental

examination on a regular basis (see Chapter 61). All adolescent and adult

patients should be asked to describe their use of tobacco (Chapter 54) and

alcohol (Chapter 52). Appropriate counseling should be offered to those

persons who smoke cigarettes, pipes, or cigars, those who use chewing

tobacco or snuff, and those who have evidence of alcohol abuse. Persons

with increased exposure to sunlight should be advised to take protective

measures when outdoors to protect their lips and skin from the harmful

effects of ultraviolet rays (see Chapter 12).



The draft update of this chapter was prepared for the U.S. Preventive

Services Task Force by Paul S. Frame, MD, based on materials prepared for

the Canadian Task Force on the Periodic Health Examination by Carl Rosati,

MD, FRCSC.



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