Please note: In 2003, the CTF updated its Grades of Recommendations to include an "I Recommendation" for situations where insufficient evidence exists to allow a recommendation to be made. (Formerly, these situations were captured under a "C Recommendation".) This change is not retroactive, and all "C Recommendations" made prior to 2003 have not been reevaluated in light of the new "I" recommendation grade. For a discussion of these recommendation grades, please link to the 2003 article in the Canadian Medical Association Journal here.
Overview
In 1979 the Canadian Task Force on the Periodic
Health Examination identified cancers of the oral cavity as a potentially
preventable cause of major morbidity and mortality. At the time, early
detection was considered possible but the quality of evidence supporting
the effectiveness of preventive strategies and the effectiveness of treatments
for oral cancers was limited (C Recommendation). Review of the evidence
from 1980 to 1993 has not changed this recommendation. However, smoking
cessation counselling is highlighted as a means of preventing oral cancer
and the recommendation to provide smoking cessation counselling is consistent
with that made in Chapter 43 which deals more generally with the prevention
of tobacco-caused disease.
Burden of Suffering
The estimated incidence of oral cancers in Canada
in 1993 was 3,120 and they accounted for 1,100 deaths, approximately 1.9%
of all cancer deaths. The peak age for developing oral cancers is in the
fifth to seventh decades with a male to female ratio of about 2.5:1. The
lifetime probability of developing and dying from oral cancers in men is
1.71% and 0.61% and for women is 0.71% and 0.27%, respectively. The potential
years of life lost (PYLL) for oral cancer was 16,000 years in Canada in
1989. Oral cancers account for significant mortality but their prevalence
is relatively low. This may affect the feasibility of large scale screening
with the adverse implications of the false positive and false negative
diagnoses generated by such a screening program.
Over 50% of oral cancers, when diagnosed, are beyond the American Joint Committee for Cancer Staging and End Results’ TNM Stage I. Consequently, there is major morbidity attributable both to the disease and to the various forms of treatment and all health status domains are affected. There is psychosocial disability in terms of appearance, self-esteem and withdrawal from familial and other social interactions. There are physical and functional disabilities in terms of personal hygiene, swallowing and maintenance of nutritional status, speaking and therapy-specific morbidities related to radical neck dissection and irradiation, thyroid and parathyroid dysfunction, mouth dryness from lack of normal secretion, osteonecrosis of facial bones and the adverse effects of chemotherapy.
Cancer rates for both the salivary gland and nasopharynx are 10-25 times higher among the Inuit than among the general Canadian population; these cancers are associated with Epstein-Barr virus infection as well as genetic, environmental and immunologic factors. Alcohol and tobacco are major risk factors for tumours of the mouth, tongue and pharynx with a diet high in fresh fruits and vegetables acting as a protective factor. Smokeless tobacco use, including snuff and chewing tobacco is important (long-term users 50 times more likely to develop cancer of the cheek and gum than non-users) although vitamin deficiencies and occupational exposures are also implicated. Smokeless tobacco has other negative health effects<1> and in the United States use has increased over the last two decades largely due to increased consumption by young males. While smokeless tobacco use is rare in Canada (overall prevalence of use under 1% in 1986), prevalences of use of 6-30% among native children (depending on age and study population) and 1-4% among non-native adolescents have been reported.
Maneuver
There have been no randomized controlled trials
to evaluate the effectiveness of oral cancer screening. In four studies,
oral physical examination had a sensitivity of 59-100%, specificity of
95.9-99.7%, positive predictive value of 15-91% and negative predictive
value of 99-100%;<2-5> positive predictive value is low. In addition
to the psychological impact of labelling a patient with a false positive
diagnosis, the added costs incurred by investigating patients so labelled
would be prohibitively high. The principal reason for this problem is the
low prevalence of oral cancers.
The use of tolonium chloride testing in conjunction with oral physical examination should increase the recorded prevalence of oral cancer in case-finding (average sensitivity 96.7% with 90.8 average specificity), however Rosenberg et al<6> demonstrate that the prevalence remains sufficiently low to limit its usefulness. Several other issues such as reliability of the screening test, compliance with screening (affected by the misconception that asymptomatic lesions are innocuous), follow-up, definitive therapy and cost effectiveness should be considered for large-scale programs. No cost effectiveness study has been undertaken to determine whether the reduction in morbidity or lives saved through treatment of oral cancers at an early stage is sufficient to offset the cost of an oral cancer screening program.
Effectiveness of Prevention and Treatment
Risk Factors for the Development of Oral
Cancers
There is compelling evidence from case-control
and cohort analytic studies, in varied geographic locations, of a causal
relationship between the use of tobacco products, the combined use of tobacco
and alcohol and the development of oral cancers.<7-16> Some of these
studies demonstrated a reduction in the observed oral cancer rates with
cessation of tobacco and/or alcohol consumption. There is good evidence
from a meta-analysis of randomized controlled trials to recommend smoking
cessation counselling (see Chapter 43 on Prevention of tobacco-caused disease).<17>
School-based programs to prevent smokeless tobacco use have had mixed results.<1,18-20> Evaluation of smokeless tobacco cessation programs has been limited, generally giving inconsistent results in small case series.<1> However, one randomized trial of 518 male smokeless tobacco users found that an intervention by dental hygienists (soft-tissue exam, advice to quit, self-help materials, video, quit date) improved quit rates at three months (32% of intervention group vs. 21% of controls, p<0.01).<21>
Oral Premalignancy
A heterogeneous group of asymptomatic oral pathological
entities with malignant potential includes dysplasia, erythroplasia, leukoplakia,
lichen planus and submucosal fibrosis. The prevalence of oral premalignancy
and its rate of malignant transformation are unknown. However, population-based
studies from the U.S., Hungary, Sweden and India have estimated it to be
1.3% to over 6% and 2.2% to 6% respectively. Rates of malignant transformation
of leukoplakia have been estimated at 2.2% to 6%. More recent prospective
studies, with longer follow-up, and in populations with a higher proportion
of dysplastic changes in their leukoplakias, suggest that the malignant
transformation rates are higher than previously believed (16.2-17.5%).
Although oral precancers are relatively infrequent and population screening
may therefore be inappropriate, their relative importance and significant
rate of malignant transformation would support case-finding strategies,
particularly in high-risk populations. Arguments for adopting these strategies
would be strengthened if supported by evidence of efficacious therapy for
oral precancers.
Primary treatment of oral leukoplakia and therapy aimed at prevention of second primary lesions have been studied in two randomized, placebo controlled chemoprevention trials of 13-cis-retinoic acid (13cRA).<22,23> These studies demonstrated a reduction in relative risk to almost 1.0 for the complete remission of leukoplakia and a 0.83 relative risk for the occurrence of second primary oral cancers suggesting that 13cRA was highly efficacious for these purposes. However, leukoplakia relapsed within 3 to 6 months after discontinuation of therapy, the rate of mild to moderate side effects was up to 79%, dose reduction was required in 18% to 47% of patients and at least temporary cessation of therapy was required in 4.5-6.8% of patients. Furthermore, an issue not addressed by the advocates of 13cRA was the teratogenicity of retinoic acid. Results of preliminary trials of low-dose maintenance therapy using 13cRA are encouraging, though follow-up to date is limited.<24>
Trials using b-carotene demonstrated reductions (up to 71%) in the occurrence of oral leukoplakia and mucosal dysplasia to a much lesser degree than that observed with 13cRA.<24-27> Adverse effects were virtually nonexistent. Current research on low dose maintenance and alternative (b-carotene) therapies may soon resolve these issues.
Effectiveness of Treatment of Invasive Oral
Cancers
The choice of therapy for early stage invasive
oral cancer is controversial. Primary surgical and radiation therapy are
often considered equivalent. While opinion varies considerably, particularly
concerning the adverse effects of both forms of therapy and their impact
on quality of life, there appears to be no difference in survival between
these therapies based on the current evidence in the literature.
Multivariate analyses, in studies of both surgical and radiation therapy, have consistently identified the stage of disease as an important prognostic factor. The 1991 American Cancer Society’s national five-year survival figures for oral cancer based on stage were, Local 75%, Regional 41% and Distant 18%.<23> Similar five-year survival statistics are provided in a review of the literature specifically addressing treatment of oral malignancies: Stage I 68-89%, Stage II 40-83%, Stage III 29-68%, Stage IV 6-36%.<23,28-35> These data suggest that there is a survival difference depending on the stage of the disease at the time of diagnosis but do not address lead-time or length-time bias. Two retrospective cohort studies report survival beyond five years.<23,28> Survival figures at 10 years demonstrate an increase in oral cancer-specific mortality raising concerns over lead-time bias. A single randomized controlled trial comparing elective versus therapeutic neck dissection for oral cavity carcinoma demonstrated an overall 70% survival rate for both groups at six years follow-up.<36> However the authors reported their results for all stages (I, II, III) combined. Thus, while lead-time bias may not have been an issue, it is not possible to determine the effect of treatment on early stage disease. Several large case series report similar five-year survival figures and identify second primary oral cancers as the leading cause of death in these patients after local or regional recurrence.<29-33,36> The rates of second primary oral cancers exceeds 36% and adds further to the confusion in interpreting the effectiveness of treatment for invasive oral cancers. Definitive conclusions regarding both the most effective form of therapy and the effectiveness of treatment for early stage oral cancers await a prospective randomized trial.
Recommendations of Others
In 1989, the U.S. Preventive Services Task Force
recommended counselling patients against the use of tobacco in any form,
particularly with heavy alcohol consumption, based on evidence linking
the adverse effects of tobacco with premalignant and malignant lesions
of the oral cavity.<37> Routine screening of asymptomatic persons for
oral cancer by primary care clinicians was not recommended. However, it
was thought to be prudent for clinicians to perform careful examinations
for cancerous lesions of the oral cavity in patients who use tobacco or
excessive amounts of alcohol, as well as in those with suspicious symptoms
or lesions detected through self-examination. These recommendations are
currently being reviewed.
The Canadian and American Dental Associations support the concept of oral cancer screening; however, neither group has recommended specific clinical practice guidelines in this regard.<38-43>
Conclusions and Recommendations
Ample evidence establishes the causal link between
use of tobacco products in any form and cancers of the aerodigestive tract,
based on extensive case-control and cohort studies. In addition, there
is good evidence supporting the effectiveness of counselling for smoking
cessation. There is good evidence to include smoking cessation counselling
in the periodic health examination to prevent oral cancer (A Recommendation).
*Although the recommendation has not changed, the
evidence review has been updated for this recommendation.
Link to recommendation table for 1999 update: Prevention of oral cancer
mortality
There is insufficient evidence, however, for inclusion
or exclusion of oral cancer screening in a periodic health examination
(C Recommendation). Annual examination by physicians and/or dentists should
be considered for men and women over 60 years of age who have known risk
factors for oral pre-malignancy and invasive oral cancers, such as tobacco
use in any form and regular alcohol consumption. Individual judgement should
be exercised regarding the use of tolonium chloride for those identified
by positive oral physical examination and referral to a specialist for
further diagnostic evaluation.
*Note: This recommendation has been updated.
Link to recommendation table for 1999 update: Prevention of oral cancer
mortality
Fair evidence exists supporting the efficacy of 13cRA in the treatment of oral leukoplakia; however, the high recurrence rates following cessation of therapy and the high rate of adverse effects limit its potential usefulness. Therapy with these agents remains investigational.
Unanswered Questions (Research
Agenda)
Further prospective studies are required to strengthen
the evidence demonstrating the effectiveness of primary prevention strategies.
Further research should be directed to determining whether current treatment modalities are in fact effective in a well designed randomized controlled trial. Once this is established then efforts to determine the reliability, validity and responsiveness of the most effective screening or case-finding maneuvers may be undertaken. Furthermore, there is evidence to suggest that screening by oral physical examination may be performed by different disciplines, using simple maneuvers. A cost effectiveness study of such a screening program is required to determine the most feasible screening strategy.
Evidence
The literature was identified with a MEDLINE
search for the years 1980 to 1993, limited to studies in the English language.
The following key words were used: mouth neoplasms, health status indicators,
population surveillance, mass screening combined with evaluation studies,
outcome and process assessment, mortality and prognosis.
This review was initiated in January 1993, and the recommendations were finalized by the Task Force in June, 1993.
Acknowledgements
Special thanks to Ms. Judy Carter and Task Force
members, Elaine Wang and William Feldman, for their patience and invaluable
assistance in preparing this manuscript.
Full Citation
Rosati C. Prevention of oral cancer. In: Canadian
Task Force on the Periodic Health Examination. Canadian
Guide to Clinical Preventive Health Care. Ottawa: Health Canada,
1994; 826-36.