- By Disease
- Complementary & Alternative Medicine
- Clinical Trials
- Screening & Detection
- Supportive Care
Oral Cancer Screening (PDQ®)
- Description of the Evidence
- Changes to This Summary (03/01/2013)
- Questions or Comments About This Summary
- About This PDQ Summary
- Get More Information From NCI
Note: Separate PDQ summaries on Oral Cancer Prevention and Lip and Oral Cavity Cancer Treatment are also available.
There is inadequate evidence to establish whether screening would result in a decrease in mortality from oral cancer.
Magnitude of Effect: No evidence of benefit or harm.
- Study Design: Evidence obtained from one randomized controlled trial.
- Internal Validity: Poor.
- Consistency: Not applicable (N/A).
- External Validity: Poor.
Harms have not been systematically studied and cannot be quantified based upon the literature. However, there are some unavoidable harms that would be associated with routine screening, including:
- Detection of cases that are already incurable, leading to increased morbidity.
- Unnecessary treatment associated with overdiagnosis.
- Psychologic consequences of false-positive tests.
- Misdiagnosis due to variability in assessment of biopsies.
Magnitude of Effect: Unknown.
- Study Design: Observational studies.
- Internal Validity: Poor.
- Consistency: N/A.
- External Validity: Poor.
Description of the Evidence
Incidence and mortality
An estimated 41,380 new cases of oral cancer will be diagnosed in the United States in 2013, and an estimated 7,890 people will die of the disease. This form of cancer accounts for about 3% of cancers in men. The overall annual incidence in the United States is about 10.8 per 100,000 men and women; the median age at diagnosis of oral cavity or pharyngeal cancer was 62 years from 2005 to 2009.
Incidence has been falling in men since 1975 and in women since 1980. However, incidence has recently been increasing for oral cancers related to human papillomavirus (HPV) infection. About 60% of oral/pharyngeal cancers are moderately advanced (regional stage) or metastatic at the time of diagnosis.
The estimated annual worldwide number of incident oral cancers is about 275,000, with an approximately 20-fold variation geographically. South and Southeast Asia (India, Sri Lanka, Pakistan, and Bangladesh), France, and Brazil have particularly high rates. In most countries, men have higher rates of oral cancer than women (due to tobacco use) and higher rates of lip cancer (due to sunlight exposure from outdoor occupations).
The primary risk factors for oral cancer in American men and women are tobacco (including smokeless tobacco) and alcohol use. Infection with HPV-16 has been associated with an excess risk of developing squamous cell carcinoma of the oropharynx.
Evidence of Benefit Associated With Screening
No population-based screening programs for oral cancers have been implemented in developed countries, although opportunistic screening or screening as part of a periodic health examination has been advocated. There are different methods of screening for oral cancers. Oral cancer occurs in a region of the body that is generally accessible to physical examination by the patient, the dentist, and the physician; and visual examination is the most common method used to detect visible lesions. Other methods have been used to augment clinical detection of oral lesions and include toluidine blue, brush biopsy, and fluorescence staining.
An inspection of the oral cavity is often part of a physical examination in a dentist's or physician's office. It has been pointed out that high-risk individuals visit their medical doctors more frequently than they visit their dentists. Although physicians are more likely to provide risk-factor counseling (such as tobacco cessation), they are less likely than dentists to perform an oral cancer examination. Overall, only a fraction (~20%) of Americans receive an oral cancer examination. Black patients, Hispanic patients, and those who have a lower level of education are less likely to have such an examination, perhaps because they lack access to medical care. An oral examination often includes looking for leukoplakia and erythroplakia lesions, which can progress to cancer. One study has shown that direct fluorescence visualization (using a simple hand-held device in the operating room) could identify subclinical high-risk fields with cancerous or precancerous changes extending up to 25 mm beyond the primary tumor in 19 of 20 patients undergoing oral surgery for invasive or in situ squamous cell tumors. However, this finding has not yet been tested in a screening setting. Data suggest that molecular markers may be useful in the prognosis of these premalignant oral lesions.
The routine examination of asymptomatic and symptomatic patients can lead to detection of earlier stage cancers and premalignant lesions. There is no definitive evidence, however, to show that this screening can reduce oral cancer mortality, and there are no randomized controlled trials (RCT) in any Western or other low-risk populations.
In a single RCT of screening versus usual care, 13 geographic clusters in the Trivandrum district of Kerala, India, were randomly assigned to receive systematic oral visual screening by trained health workers (seven screened clusters, six control clusters) every 3 years for three screening rounds during the period of 1996 to 2004. Cluster size varied from 5,177 to 12,147 (mean 8,815) participants. The number of interviewed (and analyzed) participants in the screening and control clusters were 87,829 and 80,086, respectively. During the 9-year period of the clinical trial, there were 77 deaths from oral cancer in the screening arm and 87 in the control arm. The cause-specific mortality rates were 16.4 versus 20.7 per 100,000 person-years (relative risk [RR] = 0.79; 95% confidence interval [CI], 0.51–1.22). In a subset analysis restricted to tobacco or alcohol users, the cause-specific mortality rates were 29.9 versus 45.4 per 100,000 person-years (RR = 0.66; 95% CI, 0.45–0.95). In male tobacco or alcohol users, the RR was 0.57 (95% CI, 0.35–0.93) and in female users, the RR was 0.78 (95% CI, 0.43–1.42). There was a qualitative difference in screening effect for nonusers: 3.0 versus 0.9 per 100,000 person-years in the screened and control arms (RR = 3.47; 95% CI, 0.12–96.51). Although there was a higher number of early-stage (I and II) cases in the screened arm versus the control arm (85 vs. 37), the number of late-stage (III and IV) cancers was similar (104 vs. 105). Therefore, there was not a clear, true stage shift, even though the proportion of cases with early-stage disease was higher in the screened arm.
Aside from the issue of generalizability to other populations and from the overall lack of a statistically significant result in cause-specific mortality, serious methodologic problems make interpretation of the results difficult, including lack of detail about the randomization process, lack of allocation concealment, and lack of adjustment for clustering effect. The total number of clusters randomized was small, and there were different distributions of income and household possessions between the two study arms. Withdrawals and dropouts were not clearly described. In summary, the sole randomized trial does not provide solid evidence of a cause-specific mortality benefit associated with systematic oral cavity visual examination.
Adjunctive techniques to visual examination
Techniques such as toluidine blue staining, brush biopsy/cytology, or fluorescence imaging as the primary screening tool or as an adjunct for screening have not been shown to have superior sensitivity and specificity for visual examination alone or to yield better health outcomes. In a RCT conducted in Keelung County, Taiwan, 7,975 individuals at high risk of oral cancer due to cigarette smoking or betel quid chewing were randomly assigned to receive a one-time oral cancer examination after gargling with toluidine blue or a blue placebo dye. The positive test rates were 9.5% versus 8.3%, respectively, (P = .047). The detection of premalignant lesions was not statistically different (rate ratio = 1.05; 95% CI, 0.74–1.41). The number of overall oral cancers diagnosed within the short follow-up period of 5 years was too small for valid comparison (six in each group).
The operating characteristics of the various techniques used as an adjunct to oral visual examination are not well established. A systematic literature review of toluidine blue, a variety of other visualization adjuncts, and cytopathology in the screening setting revealed a very broad range of reported sensitivities, specificities, and positive predictive values when using biopsy confirmation as the gold standard outcome. In part, this was due to varying study populations, sample size and settings, as well as criteria for positive-clinical examinations and for scoring a biopsy as positive.
Evidence of Harm Associated With Screening
Harms associated with screening for oral cancer are poorly studied in any quantifiable way. However, there are some unavoidable harms that would be associated with routine screening, including:
- Detection of cases that are already incurable, leading to increased morbidity.
- Unnecessary treatment of lesions that would not have progressed (overdiagnosis).
- Psychologic consequences of false-positive tests.
An additional potential harm is misdiagnosis and resulting under- or over-treatment, given the subjective pathology judgments in reading biopsies of oral lesions. When 87 biopsy diagnoses of oral lesions were compared between 21 local pathologists and double-reading by two of three central pathologists in a multicenter study of patients with prior upper aerodigestive tract cancers, agreement was only fair-to-good (kappa weighted-statistic = 0.59; 95% CI, 0.45–0.72). In a bivariate categorization of carcinoma in situ plus carcinoma versus less serious lesions, the agreement was poor, but with very wide CIs (kappa-statistic = 0.39; 95% CI, -0.12–0.97). The investigators in the same study analyzed an agreement between the local and central pathologists on clinically normal tissue adjacent to 67 biopsied clinically-suspicious lesions. The agreement on clinically normal tissue was better than for visibly abnormal lesions, but still not in the excellent range (kappa weighted-statistic = 0.75; 95% CI, 0.64–0.86).1American Cancer Society.: Cancer Facts and Figures 2013. Atlanta, Ga: American Cancer Society, 2013. Available online. Last accessed May 2, 2013.2Howlader N, Noone AM, Krapcho M, et al., eds.: SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations). Bethesda, Md: National Cancer Institute, 2012. Also available online. Last accessed February 21, 2013.3Warnakulasuriya S: Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 45 (4-5): 309-16, 2009 Apr-May.4Mork J, Lie AK, Glattre E, et al.: Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med 344 (15): 1125-31, 2001.5Opportunistic oral cancer screening: a management strategy for dental practice. BDA Occasional Paper 6: 1-36, 2000. Also available online. Last accessed February 28, 2013.6Smith RA, Cokkinides V, Brooks D, et al.: Cancer screening in the United States, 2011: A review of current American Cancer Society guidelines and issues in cancer screening. CA Cancer J Clin 61 (1): 8-30, 2011 Jan-Feb.7Kerr AR, Changrani JG, Gany FM, et al.: An academic dental center grapples with oral cancer disparities: current collaboration and future opportunities. J Dent Educ 68 (5): 531-41, 2004.8Warnakulasuriya S, Johnson NW, van der Waal I: Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med 36 (10): 575-80, 2007.9Brocklehurst P, Kujan O, Glenny AM, et al.: Screening programmes for the early detection and prevention of oral cancer. Cochrane Database Syst Rev (11): CD004150, 2010.10Poh CF, Zhang L, Anderson DW, et al.: Fluorescence visualization detection of field alterations in tumor margins of oral cancer patients. Clin Cancer Res 12 (22): 6716-22, 2006.11Poh CF, Zhang L, Lam WL, et al.: A high frequency of allelic loss in oral verrucous lesions may explain malignant risk. Lab Invest 81 (4): 629-34, 2001.12Screening for oral cancer. In: Fisher M, Eckhart C, eds.: Guide to Clinical Preventive Services: an Assessment of the Effectiveness of 169 Interventions. Report of the U.S. Preventive Services Task Force. Baltimore, Md: Williams & Wilkins, 1989, pp 91-94.13Antunes JL, Biazevic MG, de Araujo ME, et al.: Trends and spatial distribution of oral cancer mortality in São Paulo, Brazil, 1980-1998. Oral Oncol 37 (4): 345-50, 2001.14U.S. Preventive Services Task Force.: Screening for Oral Cancer: Recommendation Statement. Rockville, Md: U.S. Preventive Services Task Force, 2004. Available online. Last accessed February 28, 2013.15Scattoloni J: Screening for Oral Cancer: Brief Evidence Update. Rockville, Md: U.S. Preventive Services Task Force, 2004. Available online. Last accessed February 28, 2013.16Sankaranarayanan R, Mathew B, Jacob BJ, et al.: Early findings from a community-based, cluster-randomized, controlled oral cancer screening trial in Kerala, India. The Trivandrum Oral Cancer Screening Study Group. Cancer 88 (3): 664-73, 2000.17Ramadas K, Sankaranarayanan R, Jacob BJ, et al.: Interim results from a cluster randomized controlled oral cancer screening trial in Kerala, India. Oral Oncol 39 (6): 580-8, 2003.18Sankaranarayanan R, Ramadas K, Thomas G, et al.: Effect of screening on oral cancer mortality in Kerala, India: a cluster-randomised controlled trial. Lancet 365 (9475): 1927-33, 2005 Jun 4-10.19Lingen MW, Kalmar JR, Karrison T, et al.: Critical evaluation of diagnostic aids for the detection of oral cancer. Oral Oncol 44 (1): 10-22, 2008.20Su WW, Yen AM, Chiu SY, et al.: A community-based RCT for oral cancer screening with toluidine blue. J Dent Res 89 (9): 933-7, 2010.21Patton LL, Epstein JB, Kerr AR: Adjunctive techniques for oral cancer examination and lesion diagnosis: a systematic review of the literature. J Am Dent Assoc 139 (7): 896-905; quiz 993-4, 2008.22Speight PM, Zakrzewska J, Downer MC: Screening for oral cancer and precancer. Eur J Cancer B Oral Oncol 28B (1): 45-8, 1992.23Fischer DJ, Epstein JB, Morton TH, et al.: Interobserver reliability in the histopathologic diagnosis of oral pre-malignant and malignant lesions. J Oral Pathol Med 33 (2): 65-70, 2004.24Fischer DJ, Epstein JB, Morton TH Jr, et al.: Reliability of histologic diagnosis of clinically normal intraoral tissue adjacent to clinically suspicious lesions in former upper aerodigestive tract cancer patients. Oral Oncol 41 (5): 489-96, 2005.
Changes to This Summary (03/01/2013)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Description of the Evidence
Updated statistics with estimated new cases and deaths for 2013 (cited American Cancer Society as reference 1 and Howlader et al. as reference 2).
This summary is written and maintained by the PDQ Screening and Prevention Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.
Questions or Comments About This Summary
If you have questions or comments about this summary, please send them to Cancer.gov through the Web site’s Contact Form. We can respond only to email messages written in English.
About This PDQ Summary
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about oral cancer screening. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
- be discussed at a meeting,
- be cited with text, or
- replace or update an existing article that is already cited.
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Screening and Prevention Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”
The preferred citation for this PDQ summary is:
National Cancer Institute: PDQ® Oral Cancer Screening. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/screening/oral/HealthProfessional. Accessed <MM/DD/YYYY>.
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.
The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Coping with Cancer: Financial, Insurance, and Legal Information page.
More information about contacting us or receiving help with the Cancer.gov Web site can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the Web site’s Contact Form.
Get More Information From NCI
For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 8:00 a.m. to 8:00 p.m., Eastern Time. A trained Cancer Information Specialist is available to answer your questions.
The NCI's LiveHelp® online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 8:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer.
Write to us
For more information from the NCI, please write to this address:
- NCI Public Inquiries Office
- 9609 Medical Center Dr.
- Room 2E532 MSC 9760
- Bethesda, MD 20892-9760
Search the NCI Web site
The NCI Web site provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. For a quick search, use the search box in the upper right corner of each Web page. The results for a wide range of search terms will include a list of "Best Bets," editorially chosen Web pages that are most closely related to the search term entered.
There are also many other places to get materials and information about cancer treatment and services. Hospitals in your area may have information about local and regional agencies that have information on finances, getting to and from treatment, receiving care at home, and dealing with problems related to cancer treatment.
The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237).
This information was last updated on 2013-03-01