Global oral cancer screening programs review and recommendations.

ABSTRACT

The need for effective oral cancer screening techniques and programs has been widely evidenced as leading to earlier diagnosis of at-risk lesions and increasing survival rates while reducing mortality. Although various international studies have been conducted on oral cancer screening techniques, there is a distinct lack of standardization in determining which populations should be screened and which techniques should be employed. In order to compare and evaluate oral cancer screening programs, a literature review of selected international screening programs was performed based on geographic locations and the size of study (number of persons screened). The results showed that those individuals at high risk for oral cancer were mainly individuals who were smokers and excessive alcohol consumers, over the age of 30, male, of low socioeconomic status, with compromised health status (HIV/AIDS etc.), and who had a previous history of cancer. Key issues surrounding program approaches (opportunistic versus invitational); target populations; screening techniques employed; qualifications of examiners; compliance with referrals; biases, outcomes and limitations; as well as sensitivity, specificity and positive predictive values were identified and compared among the selected screening programs. Our recommendations regarding oral cancer screening focus on high-risk individuals being screened at regular intervals (preferably once per year) with the screening performed using standardized criteria for lesion identification, referral, and examiner training and calibration. Registered dental hygienists, trained and experienced in soft tissue examination, are playing a critical role in oral cancer screening. They are able to identify mucosal abnormalities or potential malignant oral lesions at an early stage, which consequently may improve treatment success and survival rates.

Keywords: mouth neoplasms; diagnosis, oral; referral and consultation; patient compliance; mass screening; smoking

RESUME

Le besoin de techniques et de programmes efficaces de depistage du cancer buccal, menant a un diagnostic precoce de lesions a risque et a une augmentation du taux de survie tout en reduisant le taux de mortalite, a ete largement demontre. Bien que differentes etudes internationales aient ete realisees, un manque important de standardisation demeure lorsqu'il s'agit de determiner quelles populations devraient faire l'objet d'un depistage et quelles techniques devraient etre utilisees. Afin de comparer et d'evaluer les programmes de depistage du cancer buccal, une analyse documentaire a ete realisee en se fondant sur les secteurs geographiques et l'effectif de l'etude (nombre de patients depistes). Les resultats ont montre que les personnes a risque eleve pour un cancer buccal ont ete identifiees comme des personnes qui: fumaient, faisaient une consommation excessive d'alcool, etaient agees de plus de 30 ans, etaient de sexe masculin, avaient un statut socioeconomique bas, avaient un etat de sante fragilisee (VIH, SIDA, etc.) ou avaient des antecedents de cancer buccal. Des points importants ont ete identifies et compares pour certains programmes de depistage selectionnes, lesquels incluaient: les approches des programmes (opportunistes versus organises); les populations ciblees; les techniques de depistage utilisees; les qualifications des sondeurs; le respect des demandes de consultation; les erreurs systemiques, les resultats et les limitations; et les valeurs de sensibilite, de specificite et les valeurs predictives positives. Nos recommandations concernant le depistage du cancer buccal se concentrent sur le depistage a intervalles reguliers (preferablement une fois par annee) chez les personnes a risque eleve par un examen realise en tenant compte des criteres standardises pour l'identification des lesions, des demandes de consultation, de la formation des sondeurs et de l'etalonnage. Les hygienistes dentaires autorise(e)s, forme(e)s et experimente(e)s ont un role important a jour dans le depistage du cancer buccal. Ils et elles sont en mesure d'identifier les anomalies des muqueuses ou les lesions buccales potentiellement malignes a un stade precoce, ce qui, par consequent, peut ameliorer les chances de reussite du traitement et les taux de survie.

INTRODUCTION

ORAL CANCER IS THE SIXTH-MOST COMMON CANCER worldwide with over 300,000 new cases diagnosed globally each year. In 2004, the World Health Report stated that the incidence of oral cancer was 10 cases per 100,000 in many developed countries including Canada and is 10 times higher in India. (1) It has one of the worst prognoses among major human cancers (< 50%, five-year survival rate), largely because these cancers are often diagnosed at late stages (stage III or IV). With the advance of treatment modalities, this dismal survival rate has not changed over several decades. Even when effective, treatment has a severe impact on the quality of life of patients including disfiguration and compromised oral functions such as eating and talking; this places significant financial pressure on both the individual and the health care system. Key to reducing mortality and morbidity of this disease is the identification of lesions-at-risk at an early and more readily treatable stage.

Most early oral cancers and pre-cancers are asymptomatic. In a recent randomized, controlled trial involving 191,873 participants in India where 87,655 subjects received at least one visual oral screening examination, a 34% reduction in mortality was observed among individuals screened over a nine-year period. (2) This underscores the value of screening, which will lead to earlier diagnoses of lesions at risk of cancer and subsequently increase survival rates and reduce mortality.

Few international studies with large cohorts have been conducted on oral cancer screening. A comprehensive comparison of these programs examining the techniques employed and the screening results would be beneficial in providing a more practical approach in strategy development and implementation of an oral cancer screening that will be suitable for various communities in Canada.

The purpose of the current review was to compare contemporary international oral cancer screening programs and techniques by considering key factors and issues. The intended outcome was to generate recommendations for further research in the field and to provide recommendations to dental professionals including the promotion of oral cancer awareness and early detection.

METHODS

This investigational review and critical literature analysis focuses on comparing international oral cancer screening programs. The literature search was conducted during the month of November 2005 using PubMed as a search engine and employing the following MeSH terms for searching: oral cancer, oral examination, referral, compliance, screening, and smoking. Journal articles dated earlier than 1980 were discarded and although four of the selected articles were dated between 1984 and 1989, the majority of the literature compiled was dated later than the year 2000 and reflected some of the most current research available. A total of 40 papers of various oral cancer screening programs were amassed. Thirty-five of these were selected for review based on the size of the screening cohort (greater than 200) and representation of a wide variety of geographic areas including Italy, India, United States, Canada, Japan, Cuba, and the United Kingdom. Various professionally recommended research articles and statements published by the World Health Organization were also included in the reviewed literature.

Throughout the literature, several common threads of information were identified, which were used to highlight consistencies and discrepancies among the screening programs reviewed. The key factors of these screening programs were compared. They include the following: approaches to screening (opportunistic versus invitational programs); screening techniques used; qualifications of individuals performing screening; sensitivity, specificity, and positive predictive values; target population; compliance with referral; biases, outcomes and research limitations. These elements were used as a basis for comparison among the studies in order to establish a set of core recommendations for screening programs and techniques.

RESULTS AND DISCUSSION

Approaches--opportunistic versus invitational programs In general, the screening programs used either an opportunistic or invitational approach in recruiting participants. Although both formats are relatively common, each has positive and negative elements that must be considered when developing a screening program.

Opportunistic programs use a pre-existing health program or clinic (that the subjects are already actively attending) to access the target population. (3,4) Invitational programs "invite" individuals from the target population to attend voluntarily via mail, posted advertisements, or house-to-house invitations. (5-8) Opportunistic screening programs commonly encompass a larger number of examinations; however, the compliance with referrals after screening is variable, from 28.8% in a Cuban study (3) to 67% for one study in India. (4) This limited compliance of referral following screening in opportunistic screening studies may be due to subjects' mandatory participation and lack of ownership.

Invitational programs, by contrast, usually have a smaller sample size and individuals who consent to a voluntary screening tend to be low-risk, more health conscious, and more compliant with referrals. (5-7) One invitational study in India found a compliance rate with referrals as high as 85%. (5)

In addition, it has been suggested that high-risk subjects (smokers, heavy drinkers, males, and the elderly) are often medically or dentally underserved and less likely to participate in an invitational study. (3,8-11) This results in a sampling bias, which is crucial to analyzing the screening outcome. (9) Opportunistic programs may be deemed more successful in terms of a more random approach with less selection bias than invitational programs. Based on these pros and cons, the selection of approach should depend largely on the purpose of the studies and the targeted population.

Sensitivity, specificity, and positive predictive value

Sensitivity is the probability that a referable lesion is present (or screening test is positive), given that the person has the disease in question (oral cancer). (12,13) Specificity is the probability that a referable lesion is not present (or screening test is negative), given that the person does not have the disease, known as the "true negative rate." Positive predictive value (PPV) is the probability that a person has the disease, given a positive test result. When sensitivity is low, there are a high number of false negatives, whereas when specificity is low, there is a high rate of false positives. Notably, when a screening program produces a high rate of false negatives (low sensitivity), the individuals may be falsely reassured and carcinogenic behaviours passively supported. (14) Conversely, when a high rate of false positives (low specificity) occurs, there may be an increase in subjects' fear and anxiety about potential treatment in the absence of true disease. With the advent of molecular assessment, histology remains the current gold standard in confirming oral cancer diagnoses. If a diagnosis is not confirmed through a biopsy, there is no way to estimate the correct sensitivity, specificity, or positive predictive value, which has been the most commonly absent information in the reviewed programs. In a small study of 292 participants in a British screening program, relatively high values for sensitivity (71%), specificity (99%), and PPV (86%) were reported. (8) These results indicate a moderate-to-low rate of false positives among individuals screened, a low rate of false negatives, and a strong probability that those who screened positive for oral cancer were accurately diagnosed.

Screening techniques

There is limited information available on the screening techniques implemented in oral cancer screening programs. Direct visual oral inspection was the most commonly used technique; however, the forms of inspection varied greatly or were unclear among programs regarding the use of lighting, retraction devises, and/or palpation. Specific details of the examination were often not provided in the research methodology, leading to notable inconsistencies among studies.

Some programs have reported the adjunctive use of visual aids, including toluidine blue staining and most recently the fluorescence visualization technique. (12,15-19) Toluidine blue dye, also known as tolonium chloride, is used to enhance the identification of suspected mucosal lesions. (12,20,21) Toluidine blue is a vital blue dye with a high affinity to nucleic acid. (12) Dysplastic changes associated with a higher concentration of nucleic acid (DNA and RNA) demonstrate higher frequency of positive staining. (19) A recent study provides strong evidence that a toluidine blue positive oral dysplastic lesion is six times more likely to become cancerous and was found to have a strong association with a high-risk molecular pattern using loss of heterozygosity. (15,19) Hence, referral for further investigation of positively stained lesions after excluding possible inflammation and infection is well supported. (12) It is worth noting that toluidine blue has been found to be a highly sensitive technique--sensitivity of 79.5% and specificity of 62%--that may produce a large proportion of false positives due to the inflammatory conditions of many lesions. (9,12,21) To improve the specificity and reduce the false positivity, a trained and experienced dental professional is required to rule out possible confounding factors.

A novel oral cancer screening technique developed by the researchers at the BC Cancer Agency is direct fluorescence visualization (FV) using a blue light. This simple hand-held device employs tissue optics to highlight mucosal abnormalities in the oral cavity. (16-18) This tool has also been used in individuals with a history of dysplasia or cancer and is currently being introduced in communities, such as the high-risk community of Vancouver's Downtown Eastside. The initial findings indicate that this tool could serve as an easy-to-use, very promising, and valuable clinical adjunct in oral cancer screening.

Qualifications of individuals performing the screening

There is a long-standing debate as to the qualifications necessary for individuals who perform the oral examinations for screening programs. The debate revolves around reproducibility, training, calibration, and cost-effectiveness. In many international studies, dentists most commonly are responsible for conducting oral examinations; however, the cost restraints are often prohibitive. As a result, trained personnel in some studies varied from grade 10 education with specific health care training to university graduates. (4,22) However, limited experience, training/education, and lack of calibration make it difficult to draw conclusions as to the feasibility and reproducibility of examinations conducted by these individuals. (2,4,10,22,23)

Due to a shortage of human resources in one India study by Mathew et al, the feasibility of oral self-examination was explored as part of an oral cancer screening program. (22) The lesions that are detected in this high-risk population with a high prevalence of oral pre-malignant lesions and cancers are known to be generally overt and easily recognizable. Due to the extensive use of known carcinogens such as betel nuts and limited access to regular screening in this area, oral lesions may become large and disfiguring tumors before they are diagnosed. Therefore, oral cancer self-examination was found to be feasible for this specific population. In populations where oral lesions are much smaller and only clinically apparent, the efficacy of self-examination remains inconclusive.

In developed countries such as Canada and the United States, dental hygienists are trained to perform oral cancer screening as part of regular dental hygiene care. (24-27) This represents an opportunistic format of oral cancer screening, however dental hygienists are also playing a valuable role in community screening initiatives. (28) Based on the knowledge and training of dental hygienists and their accessibility, dental hygienists indeed play an important role in oral cancer screening and referral.

Target population

Given the very low incidence of oral cancer in individuals who are non-smokers and who are under the age of 30, mass population screenings for oral cancer have not been widely indicated. (21,29) As a result, oral cancer screening programs generally target high-risk populations in both developed and developing countries based on the issue of cost-effectiveness.

The majority of oral cancer screening programs have been initiated in developing countries such as India, Sri Lanka, and Cuba where high-risk populations are most accessible. (2-4,10,23,30) In developed countries, high-risk populations do exist; however, the compliance rate is reportedly poor for these types of individuals. (31) Low compliance in high-risk individuals has been associated with low socio-economic status and a lack of symptoms. (31)

The mean age of subjects recruited for screening in the reviewed studies was calculated at 39.5 years (excluding the Cuba study (3) outlier where no age limits were set), the median was 35 years, and the age range was 30-60 years (table 1). The ages of subjects who screened positive were determined in only four studies due to a lack of complete reporting details in the majority of studies regarding age ranges of positively screened subjects. In the study by Ikeda et al., which investigated only the presence of oral leukoplakia and mucosal diseases, 81% of leukoplakia lesions were found in individuals [greater than or equal to] 30 years. (32) In the study by Ramadas et al., 86% of individuals with positive screening results were calculated to be [greater than or equal to] 45 years of age. (10) In the Cuba study (Fernandez et al.), the highest incidence of oral cancer was found to be in males [greater than or equal to] 50 years old. (3) In the study by Field et al., the only subject diagnosed with squamous cell carcinoma was 55 years of age while three subjects (aged [greater than or equal to] 49 years) were diagnosed with leukoplakia. (29) In summary, as indicated in most studies reviewed, high-risk populations consist of individuals over 30 years of age who are tobacco-users, heavy drinkers, and male. (3,8-11)

Low socio-economic status has been reported to be a risk factor in the development of oral cancer. This is a complicated factor that might result from a limited access to medical care for late diagnosis, and from poor nutrition and poor general health. (10,31) It is noteworthy that socioeconomic status is population-specific and cannot be applied equally to both developed and underdeveloped countries. Further investigation is necessary in order to substantiate the precise effect of social factors on the development of oral cancer.

Compliance with referrals

Achieving acceptable compliance rates is a challenge in most subject-based research, as was noted among the screening programs reviewed where compliance rates varied significantly or were not mentioned at all. It is understood that compliance may be related to a multitude of factors such as gender, age, health awareness, socio-economic status, and known oral risk habits. Nagao et al. found that compliance was poor in men over the age of 60 as well as in smokers and drinkers (6,7) whereas Sankaranarayanan et al. supported the theory that men are often less compliant than women. (23) Decreased compliance has also been attributed to negative advertisements for oral cancer screening programs that employed "scare tactics" to recruit subjects. (8) The Cuban screening program experienced poor compliance with referrals due to the government-imposed structure of the program that did not encourage ownership in the screening process--subjects were obliged to participate. (3) Interestingly, compliance has been noted to be enhanced in cases where the screening program was made convenient for the subjects such as when it was offered in close proximity to where the subjects worked. (29)

Biases and limitations

In reviewing the literature, numerous biases were identified that may have negatively impacted the outcomes of the studies. Despite efforts to select a representative sample from the given population, a disproportionate number of males versus females was noted among subjects. (6,29) As stated above, compliance often differs between males and females; therefore a gender bias has the potential to impact study outcomes. In one longitudinal study, an examiner bias and an information bias were noted as both health care workers and subjects knew whether they were of intervention or control status. (2,10,23) Since the control arm did not receive screening, this bias may have affected the conduct of the interview and possibly led to retrospective correction.

Length bias has been found to occur in cases where there is the tendency for a screening program to detect the more slowly progressive forms of a disease. (9,33) Discrepancies between mortality and survival rates of oral cancer screening programs may be due to length biases that result in the underdiagnosis of fast-growing disease. Longitudinal studies are therefore strongly indicated in order to detect both fast and slow forms of disease progression.

Overdiagnosis bias is defined as the detection of "pseudo-disease," a subclinical condition that would not have produced signs or symptoms before the subject died of other causes. (33) In any screening program, some proportion of screen-detected cases will be pseudo-disease because of competing mortality. Overdiagnosis causes the overestimation of sensitivity, specificity, and positive predictive values. This particular bias was not mentioned in any of the literature reviewed and may be a potential cause of reporting error.

SIGNIFICANT FINDINGS

Table 2 summarizes the numerous oral cancer screening programs reviewed, the purpose of each study, and the subsequent outcomes.

Various limitations of the oral cancer screening programs were identified through this literature review. Few studies provided details on screening techniques that were employed, which hinders program comparison and creates inconsistencies between programs. Sensitivity, specificity, and PPV were not consistently reported, again preventing programs from being consistently compared or contrasted. Currently, there are no standardized screening program guidelines established for age-related risk factors, detection of precursor lesions, examination techniques, or referral criteria. Despite the fact that many of these studies were longitudinal in design, survival analysis and intent-to-treat were not mentioned. This may have led to incorrect reporting of individuals lost due to dropout prior to the completion of the study.

A recent publication by the Cochrane Collaboration (May 2006) reflected a comprehensive literature search conducted to assess the effect of current screening methods on oral cancer mortality rates. (35) Although this systematic review was not originally included in the initial literature review for this paper, its subsequent publication demands reference. In this Cochrane review, 112 citations were examined; however, only one randomized controlled trial was found (Sankaranarayanan et al., 2005), which has been widely quoted due to the 34% reduction in mortality rates found among high-risk individuals who were screened as compared to the control group. (35) Despite the agreement that this reduction in mortality rates reflects positively on the advantages of oral cancer screening programs, especially in high-risk populations, the weaknesses of this longitudinal study were highlighted in the Cochrane review and echoed many of the same weaknesses mentioned in this paper. As a result, the need still remains for further well-designed longitudinal, randomized, controlled trials to investigate the outcomes of oral cancer screening in both high- and low-risk populations. It is only by amassing a significant foundation of such literature that strong guidelines for screening can be established.

RECOMMENDED STRATEGIES FOR DEVELOPING AN ORAL CANCER SCREENING PROGRAM

With regard to oral cancer screening program design, certain recommendations should be considered. Standardized criteria for lesion identification, recording, and referral should be established. As well, standardized training procedures and examiner calibrations should be established to maximize diagnostic consistency, recognizing that there are several levels of examination including visual only or visual and tactile. False positive and false negative diagnoses as well as biases must be minimized in the program design while optimizing referral compliance and outcomes. In terms of program approach, the appropriate selection of opportunistic or invitational program design must be determined for the target population in order to enhance screening outcomes. It is also important that standardized criteria for screening techniques be established and implemented in a reproducible fashion. It is advantageous to promote screening programs effectively; however; negative advertising associated with oral cancer screening should be avoided as this may reduce program attendance and compliance. To improve the cost-effectiveness of screening programs, identification of high-risk populations for screening is essential (table 3). It is therefore recommended that individuals at high risk for oral cancer be screened at regular intervals using standardized, reproducible techniques in order to achieve early detection of malignant and pre-malignant lesions as well as to promote oral cancer prevention and awareness.

THE ROLE OF THE DENTAL HYGIENIST IN ORAL CANCER PREVENTION

Traditionally, dental hygienists have been integral providers of oral health prevention and management. The primary goal of oral cancer screening is prevention so logically, dental hygienists play a critical role in oral cancer screening and early detection.

Registered dental hygienists are highly trained individuals responsible for the assessment, treatment, and maintenance of the periodontal unit. Detailed treatment planning and individualized client care including thorough intra- and extra-oral exams and careful reviewing of health history and tobacco/alcohol use allows the dental hygienist the opportunity to identify individuals at higher risk for oral cancer and perform effective screening techniques. It has been determined that early diagnosis of oral cancer leads to an excellent prognosis in treatment. Therefore regular dental hygiene visits provide a valuable setting for oral cancer screening. (37)

In many Canadian provinces and American states, it is within the dental hygiene scope of practice to identify tissue abnormalities and make referrals to an appropriate specialist, which makes oral cancer screening an important role and responsibility for every dental hygienist. Even where dental hygienists may not self-initiate, they need to be professionally prepared and responsible for oral cancer examinations and risk counselling. According to surveys in British Columbia, Nova Scotia, Maryland, North Carolina, California, and Italy, many dental hygienists--despite having received training in oral cancer screening--still report not performing oral cancer screenings on a regular basis so a gap has been identified between knowledge and clinical application of oral screening techniques. (24-27,36,38) Thus, there remains a need for continuing education for dental hygiene professionals to improve clinical perceptions and skills in detecting oral lesions that require further triage and management.

Although dental hygienists are by definition "opportunistic screeners" based on the dental clinic environment in which they regularly treat clients and perform oral cancer examinations, the opportunity also exists for dental hygienists to extend their influence to population-based screening programs. In Vancouver's Downtown Eastside, an oral cancer screening program of the area's high-risk population has been successful in screening 200 individuals and identifying 31 cases of leukoplakia, 13 (42%) of which showing positive toluidine blue staining. (28) To date, 12 of these 13 cases have been biopsied, showing 2 cancers and 8 pre-cancers. (28) This oral cancer screening program has benefited directly from the involvement of a local dental hygienist who has been actively involved in the screening process and data collection as part of her graduate research in oral cancer screening programs of high-risk populations. Dental hygienists are encouraged to join the outreach screening activities to the communities in need, to participate in health fairs or through education pathway to raise the awareness for oral cancer in general population.

Being "frontline screeners," dental hygienists should understand the nature of oral cancer, constantly update their knowledge of its detection and prevention, and most importantly, conduct oral cancer screening for all adult clients at the time of their regular dental visits for hygiene procedures. Working together with a strong commitment to change, dental hygienists have the opportunity to make a dramatic difference in the outcomes for clients with pre-malignant oral disease and oral cancer.

ACKNOWLEDGEMENTS

The authors would like to thank Professor Bonnie Craig, Dental Hygiene Program Director, Faculty of Dentistry, University of British Columbia, for her leadership in improving the dental hygiene profession in education and Denise Laronde, RDH, MSc, PhD Candidate, for her time, clinical expertise, and valuable insight.

REFERENCES

1. Petersen PE. Strengthening the prevention of oral cancer: the WHO perspective. Community Dent Oral Epidemiol. 2005;33(6):397-9.

2. Sankaranarayanan R, Ramadas K, Thomas G, et al. Effect of screening on oral cancer mortality in Kerala, India: A cluster-randomised controlled trail. Lancet. 2005;365(9475):1927-33.

3. Fernandez Garrote L, Sankaranarayanan R, Lence Anta JJ, Rodriguez Salva A, Parkin DM. An evaluation of the oral cancer control program in Cuba. Epidemiology. 1995;6(4):428-31.

4. Mehta FS, Gupta PC, Bhonsle RB, Murti PR, Daftary DK, Pindborg JJ. Detection of oral cancer using basic health workers in an area of high oral cancer incidence in India. Cancer Detect Prev. 1986;9(3-4):219-25.

5. Mathew B, Sankaranarayanan R, Sunilkumar KB, Kuruvila B, Pisani P, Krishnan Nair M. Reproducibility and validity of oral cancer visual inspection by trained health workers in the detection of oral precancer and cancer. Br J Cancer. 1997;76(3): 390-94.

6. Nagao T, Warnakulasuriya S. Annual screening for oral cancer detection. Cancer Detect Prev. 2003;27(5):333-7.

7. Nagao T, Ikeda N, Fukano H, Miyazaki H, Yano M, Warnakulasuriya S. Outcome following a population screening programme for oral cancer and precancer in Japan. Oral Oncol. 2000;36(4):340-6.

8. Downer MC, Evans AW, Hughes Hallett CM, Jullien JA, Speight PM, Zakrzewska JM. Evaluation of screening for oral cancer and precancer in company headquarters. Community Dent Oral Epidemiol. 1995;23(2):84-8.

9. Warnakulasuriya KAAS, Johnson NW. Strengths and weaknesses of screening programmes for oral malignancies and potentially malignant lesions. Eur J Cancer Prev. 1996;5(2):93-8.

10. Ramadas K, Sankaranarayanan R, Jacob B, et al. Interim results from a cluster randomized controlled oral cancer screening trial in Kerala, India. Oral Oncol. 2003;39(6):580-8.

11. Epstein JB, Zhang L, Rosin M. Advances in the diagnosis of oral premalignant and malignant lesions. J Can Dent Assoc. 2002;68(10):617-21.

12. Rosenberg D, Cretin S. Use of meta-analysis to evaluate tolonium chloride in oral cancer screening. Oral Surg Oral Med Oral Pathol. 1989;67(5):621-7.

13. Willoughby TL. Medical biostatics: sensitivity, specificity and predictive values [on-line]. [Cited 2006 Jan 3.] Available from: http://research.med.umkc.edu/tlwbiostats/sens_specif_pred-val.html.

14. Lavelle CLB, Scully C. Criteria to rationalize population screening to control oral cancer. Oral Oncol. 2004;41(1):11-6.

15. BC Cancer Agency. 2005/09/01: Detecting dangerous oral cancer sooner [press release] [cited 2006 Feb 28]. Vancouver: BCCA; 2005 Sep 1. Available from: www.bccancer.bc.ca/ABCCA/NewsCentre/NewsArchive/2005/oralcancerstudy.htm.

16. Lane MP, Gilhuly T, Whitehead P, et al. Simple device for the direct visualization of oral-cavity tissue fluorescence. J Biomed.Opt. 2006;11(2):024006.

17. Poh CF, Ng SP, Williams PM, et al. Detection of clinically occult high-risk oral premalignant disease using direct auto-fluorescent visualization. Head Neck. 2007;29(1):71-6.

18. Poh CF, Zhang L, Anderson DW, et al. Fluorescence visualization detection of field alterations in tumor margins of oral cancer patients. Clin Cancer Res. 20061;12 (22):6716-22.

19. Zhang L, Williams PM, Poh CF, et al. Toluidine blue staining identifies high-risk primary oral premalignant lesions with poor outcome. Cancer Res. 2005;65(17):8017-21.

20. Franceschi S, Brazan L Talamini R. Screening for cancer of the head and neck: If not now, when? Oral Oncol. 1997;33(5):313-6.

21. Mashberg A, Barsa P. Screening for oral and oropharyngeal squamous carcinomas. CA Cancer J Clin. 1984;34(5):262-8.

22. Mathew B, Sankaranarayanan R, Wesley R, Nair MK. Evaluation of mouth self-examination in the control of oral cancer. Br J Cancer. 1995;71(2):397-9.

23. Sankaranarayanan R, Mathew B, Jacob B, et al. Early findings from a community-based, cluster-randomized, controlled oral cancer screening trial in Kerala, India. Cancer. 2000;88(3):664-73.

24. Forrest JL, Horowitz AM, Shmuely Y. Dental hygienists' knowledge, opinions, and practices related to oral and pharyngeal cancer risk assessment. J Dent Hyg. 2001;75(4):271-81.

25. Forrest JL, Drury TE, Horowitz AM. U.S. dental hygienists' knowledge and opinions related to providing oral cancer examinations. J Cancer Educ. 2001;16(3):150-6.

26. Ashe TE, Elter JR, Southerland JH, Strauss RP, Patton LL. North Carolina dental hygienists' oral cancer knowledge and opinions: implications for education. J Cancer Educ. 2006;21(3):151-6.

27. Clovis JB, Horowitz AM, Poel DH. Oral and pharyngeal cancer: knowledge, opinions and practices of dental hygienists in British Columbia and Nova Scotia. Probe 2003;37(3):109-22.

28. Poh CF, Currie BL, Hislop G, Sikorski S, Zhang L, MacAulay C, Rosin MP. Integration of new technology into a high-risk underserved community: pilot studies within an oral cancer screening clinic. Paper presented at AACR Frontiers in Cancer Prevention Research conference; 2006 Nov 12-15; Boston, Massachusetts.

29. Field EA, Morrison T, Darling AE, Parr TA, Zakrzewska JM. Oral mucosal screening as an integral part of routine dental care. Br Dent J. 1995;179(7):262-6.

30. Warnakulasuriya KAAS, Nanayakkara BG. Reproducibility of an oral cancer and precancer detection program using primary health care model in Sri Lanka. Cancer Detect Prev. 1991;15(5):331-4.

31. Talamini R, Barzan L, Franceschi S, Caruso G, Gasparin A, Comoretto R. Determinants of compliance with an early detection programme for oral cancer of the head and neck in north-eastern Italy. Eur J Cancer B Oral Oncol. 1994;30B(6):415-8.

32. Ikeda N, Ishii T, Iida S, Kawai T. Epidemiological study of oral leukoplakia based on mass screening for oral mucosal diseases in a selected Japanese population. Community Dental Oral Epidemiol. 1991;19(3):160-3.

33. Black WC. Overdiagnosis: An underrecognized cause of confusion and harm in cancer screening. J Natl Cancer Inst. 2000;92(16):1280-2.

34. Bouquot JE. Common oral lesions found during a mass screening examination. J Am Dent Assoc. 1986;112(1):50-7.

35. Kujan O, Glenny AM, Oliver RJ, Thakker N, Sloan P. Screening programmes for the early detection and prevention of oral cancer. Cochrane Database Syst Rev. 2006;3:CD004150.

36. Nicotera G, Gnisci F, Bianco A, Angelillo IF. Dental hygienists and oral cancer prevention: knowledge, attitudes and behaviors in Italy. Oral Oncol. 2004;40(6):638-44.

37. Cormier L, Lavelle CL: The dental hygienist's role in screening for oral cancer. Probe. 1995;29(2):53-6, 58-9.

38. Tinoco JA, Silva AF, Oliveira CA, Rapoport A, Fava AS, Souza RP. Human papilloma virus (HPV) infection and its relation with squamous cell carcinoma or the mouth and oropharynx. Rev Assoc Med Bras. 2004;50(3):252-6. Epub 2004 Oct 21.

This article has been peer reviewed.

by Heather Biggar, RDH, BSC(DH),* Amanda Forrest, RDH, BSC(DH), ([dagger]) and Catherine F. Poh, DDS, PhD([section])

* MSc Candidate, Faculty of Dentistry, University of British Columbia

[dagger] Faculty of Dentistry, University of British Columbia

[section] Assistant Professor, Faculty of Dentistry, University of British Columbia

                        Number of
Study                   subjects    Incidence; age*

Ikeda et al., 1991           3,131  81%; [greater than or equal to] 30
  (Japan) (32)                      years of age
Ramadas et al., 2003       114,601  86%; [greater than or equal to] 45
  (India) (10)--                    years of age
  interim findings
Fernandez et al., 1995  12,990,677  27%; [greater than or equal to] 15
  (Cuba) (3)                        years old (all subjects
                                    [greater than or equal to] 15 years
                                    with dental concerns were screened)
Field et al., 1995           1,369  5%; [greater than or equal to] 49
  (UK) (29)                         years (only three cases of
                                    leukoplakia detected)

* Incidence: percentage of leukoplakia of the screened subjects; Age:
Age of leukoplakia detected.
Table 1. Age-related incidence of oral leukoplakia

Study                Objective          Significant Findings

Bouquot, 1986        To characterize    The 30 most common lesions were
  (Minnesota) (34)   the prevalence of  ranked according to gender-
32,000 subjects      the most common    specific prevalence rates from
                     oral lesions       the studies included in this
                                        comparison. Leukoplakia
                                        (incidence: 29.1 per 1,000) was
                                        the most common mucosal lesion
                                        and oral carcinoma (incidence:
                                        1.1 per 1,000) was 24th overall.
Ikeda et al.,        1. To show the     Results suggested that, to carry
  1991 (Japan) (32)  epidemiological    out an efficient oral health
3,131 subjects       status of oral     program in Japan, it would be
                     mucosal lesions,   better to limit mass screening
                     specifically       for leukoplakia to men
                     leukoplakia, in a  [greater than or equal to] 30 &
                     selected Japanese  women
                     population         [greater than or equal to] 40.
                     2. To estimate
                     the validity of
                     the diagnosis of
                     oral leukoplakia
                     by general
                     practitioners
Talamini et al.,     To quantify the    The identification of high-risk
  1994 (Italy) (31)  relationship       individuals is expensive and the
627 subjects         between various    compliance with a head and neck
                     individuals'       cancer early detection program
                     characteristics    is relatively low, especially in
                     and compliance     smokers.
                     with an ear,
                     nose, and throat
                     professional
                     examination
Field et al.,        To assess the      A methodical and thorough
  1995 (UK) (29)     feasibility of     examination of the oral mucosa
1,369 subjects       conducting a       can be realistically carried out
                     systematic oral    as part of a routine dental
                     mucosa             inspection. Feasibility was
                     examination at     determined and the program is to
                     company            be expanded to screen all
                     headquarters, to   employees of the company.
                     describe the
                     target screening
                     population, to
                     measure the
                     participation
                     rate, and to
                     determine initial
                     results
Sankaranaranayanan   To assess the      34% [down arrow] in mortality
  et al., 2005       effect of visual   and 50% [up arrow] in 5-year
  (India) (2)        screening on oral  survival rate in the
191,873 subjects     cancer mortality   intervention group (screened
                     in high-risk       high-risk individuals)
                     individuals

Table 2. International oral cancer screening programs: outcomes

Heavy smokers and/or excessive alcohol consumers
Individuals over 30 years of age
Male gender
Compromised health status (HIV/AIDS, Hepatitis B carrier, Hepatitis C
infection)
Previous history of oral cancer
Nutrition factors (especially low consumption of fruits and vegetables)

Table 3. Characteristics of high-risk populations (3,8-11,27,36)