Draft Recommendation Statement
Note: This draft Recommendation Statement is not the final recommendation of the U.S. Preventive Services Task Force. This draft is distributed solely for the purpose of pre-release review. It has not been disseminated otherwise by the USPSTF. It does not represent and should not be interpreted to represent a USPSTF determination or policy.
This draft Recommendation Statement is based on an evidence review available at http://www.uspreventiveservicestaskforce.org/uspstf13/oralcan/oralcanes.pdf (PDF File, 540 KB; PDF Help).
The USPSTF makes recommendations about the effectiveness of specific clinical preventive services for patients without related signs or symptoms.
It bases its recommendations on the evidence of both the benefits and harms of the service, and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment.
The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decisionmaking to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.
This draft Recommendation Statement is available for comment from April 9 until May 6, 2013, at 5:00 PM ET. You may wish to read the entire Recommendation Statement before you comment.
Screening for Oral Cancer: U.S. Preventive Services Task Force Recommendation Statement
DRAFT
Summary of Recommendation and Evidence
The U.S. Preventive Services Task Force (USPSTF) concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for oral cancer in asymptomatic adults.
This is an I statement.
Go to the Clinical Considerations section for additional information about suggestions for practice regarding the I statement.
Table 1 describes the USPSTF grades, and Table 2 describes the USPSTF classification of levels of certainty about net benefit.
Rationale
Importance
Oral cancer includes cancers of the lip, oral cavity, and pharynx. Ninety percent of all cases of oral cancer are classified as squamous cell carcinoma (1). The American Cancer Society estimates that there will be 36,000 new cases and 6,850 deaths from oral cancer in 2013 (2). At the time of diagnosis, more than 50% of people with oral cancer have regional or distant metastases (3). Screening for oral cancer may be helpful if potentially malignant disorders could be identified earlier and treated successfully.
The incidence and mortality rate for oral cancer has been decreasing in the United States because of reduced tobacco and alcohol use; however, human papillomavirus (HPV)–related oropharyngeal cancer has begun to increase in incidence. As the epidemiology of HPV-related oropharyngeal cancer continues to unfold, it could have an important effect on the identification of other high-risk populations that may benefit from screening.
Detection
The USPSTF found inadequate evidence that the oral screening examination accurately detects oral cancer.
Benefits of Detection and Early Treatment
The USPSTF found inadequate evidence that screening for oral cancer and treatment of screen-detected oral cancer improves morbidity or mortality.
Harms of Detection and Early Treatment
There is inadequate evidence on the harms of screening. No study reported on harms from the screening test or from false-positive or false-negative test results.
Potential diagnostic harms are primarily related to the harms of biopsy for suspected oral cancer or its potential precursors. Harms of treatment for screen-detected oral cancer and its potentially malignant disorders (i.e., leukoplakia, erythroplakia) may result from complications of surgery (first-line treatment), radiation, and chemotherapy. The natural history of screen-detected oral cancer or potentially malignant disorders is unclear, and thus the magnitude of overdiagnosis due to screening is not known.
USPSTF Assessment
The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of screening for oral cancer in asymptomatic adults.
Clinical Considerations
Patient Population Under Consideration
This recommendation applies to adults age 18 years or older who are seen by primary care providers.
Assessment of Risk
Tobacco and alcohol use are major risk factors for oral cancer. Worldwide, 20% to 30% of oral cancer cases are attributable to cigarette smoking (1). In the United States, up to 75% of oral cancer cases may be attributable to tobacco and alcohol use (4). Recently, sexually transmitted oral HPV infection (HPV-16) has been recognized as an increasing risk factor for developing oropharyngeal cancer, a subset of oral cancer. Worldwide, the prevalence of HPV in oral squamous cell carcinoma is 23.5%. The prevalence of oral HPV infection is associated with age, sex, number of sexual partners, and number of cigarettes smoked per day. The effectiveness of multifactorial risk assessment and screening is not known (1).
Screening Tests
The primary screening test for oral cancer is a systematic clinical- or self-examination, including inspection and palpation of the oral cavity. HPV-related oral cancer is usually located at the oropharynx (the tonsil and base of the tongue). Additional tests have been proposed as adjuncts to the screening examination, such as toluidine blue dye staining, chemiluminescent and autofluorescent lighting devices, and brush cytopathology. These screening tests, as well as adjunct tests, have not been adequately tested in primary care nondental settings.
Suggestions for Practice Regarding the I Statement
This recommendation is intended for primary care providers. Dentists and dental care providers, by their profession, examine the oral cavity during the clinical encounter. In deciding whether to screen for oral cancer, primary care providers should consider the following.
Potential preventable burden. Up to 75% of oral cancer cases may be attributed to tobacco and alcohol use (4). Since 1979, the incidence rate of cancer of the oral cavity in the United States has decreased because of declines in cigarette smoking and alcohol use. However, during this same time period, the incidence of HPV-related oral squamous cell carcinoma has increased. From 1998 to 2004, HPV-unrelated oral cancer has declined from 2.0 cases per 100,000 persons to 1.0 case per 100,000 persons; HPV-related oral cancer has increased more than threefold, from 0.8 cases per 100,000 persons to 2.6 cases per 100,000 persons (5). Patients with HPV-related oral cancer are on average 5 years younger at diagnosis and have improved survival compared with patients with HPV-negative oral cancer (6).
The overall oral HPV prevalence is estimated to be 6.9% in adults ages 14 to 69 years in the United States. However, HPV prevalence can be as high as 20% for those who have more than 20 lifetime sexual partners or current tobacco use (>1 pack of cigarettes per day). The prevalence of type-specific HPV-16 is 1% in adults ages 14 to 69 years (an estimated 2.13 million infected individuals). HPV-16 accounts for at least 90% of all HPV-related cancer cases (5). Therefore, the rising role of HPV oral infection as a risk factor for oral cancer may warrant future assessment of the independent effect of HPV-16 on incidence and outcomes of oral cancer and the effects of screening individuals who are positive for HPV-16.
Potential harms. Suspected oral cancer or its precursors (such as erythroplakia, because of its high risk of cancer transformation) detected by examination require confirmation by tissue biopsy, which may lead to some harms. Harms of treatment for screen-detected oral cancer and its potential precursors (leukoplakia, erythroplakia) may result from complications of surgery, radiotherapy, and chemotherapy. The natural history of screen-detected oral cancer is not well understood and, as a result, the harms from overdiagnosis and overtreatment are not known.
Current practice. In a 2008 survey of U.S. adults, 29.4% of adults age 18 years or older reported ever having an oral cancer examination in which a doctor, dentist, or other health professional pulled on their tongue or palpated their neck. It is not known what percentage of these examinations were conducted by dentists rather than doctors or other health professionals. Adults age 40 years or older were more likely to have ever had an examination than those ages 18 to 39 years, despite smoking status. Adults who were most at risk for oral cancer (current smokers age 40 years or older) were less likely to have ever had an oral cancer examination compared with former smokers or adults who had never smoked (1).
Other Approaches to Prevention
The USPSTF recommends that clinicians screen all adults for tobacco use, recommend against tobacco use, and provide tobacco cessation interventions for those who use tobacco products (7). The USPSTF also recommends the use of screening and behavioral counseling interventions in primary care settings in order to reduce alcohol misuse by adults (8).
Other Considerations
Research Needs and Gaps
One of the most important research needs is a randomized, controlled trial assessing the benefits and harms of oral cancer screening among individuals at increased risk, especially those with a history of tobacco and heavy alcohol use as well as infection with HPV-16. Research is needed to determine the accuracy and impact of screening by primary care providers, dental hygienists, dentists, or other trained individuals among U.S. patients at increased risk. Also needed is longitudinal followup of screening studies applicable to the United States that would demonstrate the screening impact on oral cancer. If HPV continues to become a more significant risk factor for oral cancer, the benefits of screening and selection of high-risk populations that incorporates HPV status will need to be assessed. The oral examination for HPV-unrelated lesions is performed in the forward part of the mouth, but HPV-related lesions are more tonsillar and pharyngeal. As the epidemiology evolves, the best type of screening examination will have to be determined. In addition, given the higher risks of mortality from oral cancer among African Americans and men, more research is warranted regarding the risks and benefits of screening among these particular high-risk populations.
Discussion
Burden of Disease
Based on 2004 to 2008 Surveillance Epidemiology and End Results data, the overall age-adjusted incidence rate of oral cancer in the United States was 10.6 cases per 100,000 persons and the age-adjusted mortality rate was 2.5 deaths per 100,000 persons per year (1). Nearly three fourths of all oral cancer cases occur in men, making it the eighth most common cancer in men (14th most common cancer in women) in the United States.
More than half of all persons with oral cancer have regional or distant metastases at the time of diagnosis. Relative 5-year survival is 82.4% for localized disease, 55.5% for regional lymph node spread, and 33.2% for distant metastases (1, 3). Patients with HPV-positive oral cancer are diagnosed an average 5 years younger and have improved survival compared with patients with HPV-negative oral cancer (4).
African American men and women previously had higher incidence rates of oral cancer than white men and women. Current data, however, indicate a change in racial/ethnic incidence rates such that white men and women now have higher incidence rates than African American men and women. This change in incidence is ascribed to increases in HPV-related oral cancer among whites, along with a reduction in HPV-related and HPV-unrelated oral cancer among African Americans. American Indian/Alaska Native, Asian/Pacific Islander, and Latino men and women all have lower incidence rates than white and African American men and women. Mortality rates are substantially higher in African Americans and men; among men, mortality rates in American Indian/Alaska Natives are about the same as whites, but Asians/Pacific Islanders and Latinos have lower mortality rates than whites (3).
Scope of Review
The previous recommendation of the USPSTF found no evidence that screening for oral cancer led to improved health outcomes and found limited information about the accuracy of the oral examination for detecting cancer or premalignant lesions (9). To update its previous recommendation, the USPSTF reviewed evidence to answer the following questions: 1) Does screening for oral cancer reduce morbidity or mortality? and 2) How accurate is the screening oral examination for identifying oral cancer or potentially malignant disorders that have a high likelihood of progression to oral cancer?
Accuracy of Screening Tests
No evidence was found on screening for oral cancer in the general or high-risk U.S. population. Seven studies (n=49,120) examined the performance characteristics of the oral screening examination. These studies were generally conducted in settings with an increased incidence of and mortality from oral cancer (India, Taiwan) compared with U.S. rates. The studies also had considerable heterogeneity and demonstrated great variation in test performance characteristics (1).
Across the seven studies, sensitivity for oral cancer or potentially malignant disorders ranged from 18% to 94.3% and specificity from 54% to 99.9%. The positive predictive value ranged from 17% to 86.6% and the negative predictive value from 73% to 99.3% (1).
Two studies in the United Kingdom looked at oral examinations performed by general dentists among older adults (age 40 years or older) at increased risk because of alcohol and tobacco use and a mixed sample with unknown risk factors. The dental examination in the high-risk sample (n=2,027) showed a sensitivity of 74%, a specificity of 99%, and a positive predictive value of 67%, while the study of patients with unknown risk factors found a sensitivity of 71%, a specificity of 99%, and a positive predictive value of 86%. Although the patients in the U.K. study may be similar to the U.S. population, the results of these studies were limited by an imperfect reference standard (comparison with a “more expert” examiner), by combining the detection of potentially malignant disorders with oral cancer, and an unclear delineation of high-risk status. These results would need to be confirmed by studies with longitudinal followup (1).
When compared with expert or trained screening examinations, self-examinations in two studies performed in India and the United Kingdom were not very sensitive. Toluidine blue was not found to significantly improve screening for premalignant or malignant lesions, did not affect the incidence of oral cancer, and did not improve outcomes (one study) (1).
Effectiveness of Early Detection and/or Treatment
The USPSTF found no direct evidence on whether screening reduces morbidity or mortality in general or high-risk U.S. populations.
One fair-quality randomized, controlled trial of home-based screening for oral cancer by advanced health workers (n=191,873) conducted in Kerala, India found no statistical difference in oral cancer mortality rates between screening and control groups after 9 years of followup (relative risk [RR], 0.79 [95% CI, 0.51 to 1.22]) (1, 10).
Screened subjects had oral cancer diagnosis at earlier stages, with a greater 5-year survival than control subjects, possibly a result of lead-time bias (1, 10).
A post hoc subgroup analysis of participants (n=84,600) in the Kerala study who reported tobacco and alcohol use found a significant reduction in oral cancer mortality rates in those assigned to the screening group (RR, 0.66 [95% CI, 0.45 to 0.95]). However, high-quality analysis was not conducted in the subgroup. The results of the overall study and the post hoc subgroup analysis do not provide sufficient evidence on screening because of limited applicability to the U.S. population and methodological limitations, such as an inadequate accounting for clustering in the results, low compliance with followup, imbalance in baseline risk factors, possible lead-time and length-time bias, and not reporting harms of screening or how the lesions were treated. In addition, these trial participants commonly chewed pan (a carcinogenic compound containing areca nut and betel leaf), which is not used in the United States and affects the generalizability of this study. India also has higher oral cancer incidence, prevalence, and mortality, as well as a different health care system compared with the United States, which also impacts the applicability of the study results in the U.S. population (1, 10).
Potential Harms of Screening and/or Treatment
A potentially important harm of screening includes the adverse effects from biopsies or surgeries performed for oral lesions that would have regressed spontaneously or not have progressed to cancer during a patient's lifetime (overdiagnosis and overtreatment). The USPSTF found insufficient evidence on harms from the screening test or from false-positive or false-negative test results.
Estimate of Magnitude of Net Benefit
The USPSTF found inadequate evidence on the diagnostic accuracy, benefits, and harms of screening for oral cancer. Therefore, the USPSTF was unable to determine the balance of benefits and harms.
How Does Evidence Fit With Biological Understanding?
The oral cancer examination is designed to detect oral cancer or potentially malignant disorders at earlier stages. However, visual examination or biopsy cannot distinguish potentially malignant disorders from those lesions that may spontaneously regress or not progress (overdiagnosis), and there is a lack of evidence that earlier treatment improves health outcomes. The total incidence of oral cancer is decreasing. Many cases of oral cancer that do occur arise in individuals at increased risk because of tobacco and alcohol use. However, our understanding of the risk profile of oral cancer is evolving as we learn more about the association between HPV and oral cancer. This changing epidemiology may also affect the natural history and clinical outcomes, since patients with HPV-positive oral cancer are generally diagnosed younger and survive longer compared with patients with HPV-negative oral cancer.
Recommendations of Other Groups
The American Academy of Family Physicians found insufficient evidence to recommend for or against screening for oral cancer (11). The American Cancer Society recommends that adults age 20 years and older who have periodic health examinations should have the oral cavity examined as part of a cancer-related checkup (12). The American Dental Association recommends that providers remain alert for signs of potentially malignant lesions or early-stage cancer in patients during routine examinations, particularly for patients with a history of tobacco or heavy alcohol use (13).
Table 1: What the Grades Mean and Suggestions for Practice
Table 2: Levels of Certainty Regarding Net Benefit
| Level of Certainty* | Description |
|---|---|
| High | The available evidence usually includes consistent results from well-designed, well-conducted studies in representative primary care populations. These studies assess the effects of the preventive service on health outcomes. This conclusion is therefore unlikely to be strongly affected by the results of future studies. |
| Moderate | The available evidence is sufficient to determine the effects of the preventive service on health outcomes, but confidence in the estimate is constrained by factors such as:
As more information becomes available, the magnitude or direction of the observed effect could change, and this change may be large enough to alter the conclusion. |
| Low | The available evidence is insufficient to assess effects on health outcomes. Evidence is insufficient because of:
More information may allow an estimation of effects on health outcomes. |
*The U.S. Preventive Services Task Force defines certainty as "likelihood that the USPSTF assessment of the net benefit of a preventive service is correct." The net benefit is defined as benefit minus harm of the preventive service as implemented in a general, primary care population. The USPSTF assigns a certainty level based on the nature of the overall evidence available to assess the net benefit of a preventive service.
References
1. Olson CM, Burda BU, Beil T, Whitlock EP. Screening for Oral Cancer: A Targeted Evidence Update for the U.S. Preventive Services Task Force. Evidence Synthesis No. 102. AHRQ Publication No. 13-05186-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; April 2013.
2. American Cancer Society. Oral Cavity and Oropharyngeal Cancer. Atlanta: American Cancer Society; 2013. Accessed at http://www.cancer.org/cancer/oralcavityandoropharyngealcancer/detailedguide/oral-cavity-and-oropharyngeal-cancer-key-statistics on 2 April 2013.
3. National Cancer Institute. SEER Stat Fact Sheets: Oral Cavity and Pharynx. Bethesda, MD: National Cancer Institute; 2012. Accessed at http://seer.cancer.gov/statfacts/html/oralcav.html on 2 April 2013.
4. Blot WJ, McLaughlin JK, Winn DM, Austin DF, Greenberg RS, Preston-Martin S, et al. Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res. 1988;48(11):3282-7.
5. Gillison ML, Broutian T, Pickard RK, Tong ZY, Xiao W, Kahle L, et al. Prevalence of oral HPV infection in the United States, 2009-2010. JAMA. 2012;307(7):693-703.
6. Chaturvedi AK, Engels EA, Anderson WF, Gillison ML. Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Onocol. 2008;26(4):612-9.
7. U.S. Preventive Services Task Force. Counseling and interventions to prevent tobacco use and tobacco-caused disease in adults and pregnant women: U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern Med. 2009;150(8):551-5.
8. U.S. Preventive Services Task Force. Screening and behavioral counseling interventions in primary care to reduce alcohol misuse: recommendation statement. Ann Intern Med. 2004;140(7):554-6.
9. U.S. Preventive Services Task Force. Screening for Oral Cancer: Recommendation Statement. AHRQ Pub. No. 05-0564-A. Rockville, MD: Agency for Healthcare Research and Quality; 2004.
10. Sankaranarayanan R, Ramadas K, Thomas G, Muwonge R, Thara S, Mathew B, et al. Effect of screening on oral cancer mortality in Kerala, India: a cluster-randomised controlled trial. Lancet. 2005;365(9475):1927-33.
11. American Academy of Family Physicians. Oral Cancer. Leawood, KS: American Academy of Family Physicians; 2004. Accessed at http://www.aafp.org/online/en/home/clinical/exam/oralcancer.html on 2 April 2013.
12. American Cancer Society. American Cancer Society Guidelines for the Early Detection of Cancer. Atlanta: American Cancer Society; 2013. Accessed at http://www.cancer.org/healthy/findcancerearly/cancerscreeningguidelines/american-cancer-society-guidelines-for-the-early-detection-of-cancer on 2 April 2013.
13. Rethman MP, Carpenter W, Cohen EE, Epstein J, Evans CA, Flaitz CM, et al. Evidence-based clinical recommendations regarding screening for oral squamous cell carcinomas. J Am Dent Assoc. 2010;141(5):509-20.
AHRQ Publication No. 13-05186-EF-2
Current as of April 2013
Internet Citation:
U.S. Preventive Services Task Force. Screening for Oral Cancer: Draft Recommendation Statement. AHRQ Publication No. 13-05186-EF-2. http://www.uspreventiveservicestaskforce.org/draftrec2.htm
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