ViziLite Screening: Does It Make Sense?

Stephen Barrett, M.D.

ViziLite Plus is a 5-minute test that uses fluorescent light to help dentists spot abnormal changes in the mucous membranes that line the inside of the mouth and throat. The FDA has given 510(k) marketing clearance for testing people "at increased risk" for oral cancer. Zila Pharmaceuticals is aggressively promoting the test with statements that (a) "the death rate from oral cancer is increasing," (b) "one American dies every hour" from the disease," (c) "oral cancer is far too often discovered in late stage development," (d) "early detection and diagnosis can make a tremendous difference in life expectancy" and "the ViziLite Plus exam can help your dentist or hygienist identify abnormal tissue, that might develop into oral cancer." The key consideration, however, should be whether ViziLite-assisted screening is more effective than standard screening in which the dentist looks with the naked eye using ordinary (incandescent) light. So far, the answer seems to be no.

Background History

ViziLite equipment was developed by the Trylon Corporation for use in detecting abnormal growths on the uterine cervix. In 2001, the FDA cleared the ViziLite™ Comprehensive Examination Tray for marketing "when used in combination with conventional visual oral mucosal examination by health care providers" for "identification, evaluation, and monitoring of oral mucosal abnormalities in a patient population at increased risk for oral cancer." [1] Shortly afterward, Zila Pharmaceuticals announced that it had acquired permanent marketing rights from Trylon [2].

In 2005, the FDA cleared the ViziLite Blue Oral Exam Product, which consists of ViziLite and ViziLite Blue Oral Lesion Identification and Marking System. The 510(k) clearance document states:

The Vizilite (Orallite) is a chemiluminescent light source system indicated for use as an adjunct to conventional oral mucosal screening by trained health care providers for the identification, evaluation, and monitoring of oral mucosal abnormalities in a population at increased risk for oral cancer.

The Vizilite Blue Oral lesion Identification and Marking-System, is a three-component swab system which is indicated as an adjunct to the Vizilite Test for oral mucosa lesions, for further evaluation and monitoring of lesions by providing physical marking of lesions already differentially identified with ViziLite in a population at increased risk for oral cancer

The Vizilite Blue Oral lesion Identification and Marking System is not being proposed for use in the initial oral mucosal examination without initial lesion identification with ViziLite. Furthermore, this ViziLite Blue Oral Lesion Identification and Marking System is not intended to be used as an indicator of lesions warranting further study, including biopsy. Whether a lesion is marked with the dye or not should not alter the clinician's clinical behavior as dictated by the results of the ViziLite examination. The marking dye, when positive, acts as a lesion marker that allows for the removal of the Vizilite device while preserving the anatomic character of the lesion [3].

Zila's current product, which includes the light and tissue-dye system cleared by the FDA in 2005, is now called ViziLite Plus. For several years, the company maintained a Web-based directory of dentists who offered the test. The number listed in the directory rose from about 6,200 in April 2007 to about 13,000 in December 2008, but the directory is no longer online. "Certification" is available to dentists who (a) have purchased at least 60 test kits, (b) have used the test for at least one year, (c) have done at least 40 tests, (d) have reviewed the ViziLite Training CD, and (e) use the ViziLite's patient brochure, consent form, and mouth map. Dental hygienists who satisfy these requirements (except for the minimum purchase) are also eligible for certification. Proven competence in doing the examinations does not appear to be a requirement.

Certification entitles the dental office to receive:

Vizilite's Online Screening Test

For several years, the ViziLite Web site contained a test that provides the company's view of who needs testing.

Based on age alone, the test categorized everyone over 18 as "increased risk" and everyone over 40 as "high risk" and recommends annual ViziLite screening. The test also recommended annual screening for everyone who answers "yes" to questions 2, 3, or 4. Because the incidence of oral cancer is not high, I questioned whether it was appropriate to classify the majority of American adults as "increased" or "high" risk. (For one thing, how can half the people in the country be "high risk" for a relatively uncommon disease?) I doubt that the FDA envisioned Zila's promotional strategy when it cleared the ViziLite for marketing. Searching online, however, I could not locate any government regulation or guideline that defines "increased" or "high" risk. In 2011, I noticed that the test was no longer posted to the company's Web site.

ViziLite kits are offered to dentists for $19.95 to $29.95 each, depending on the number purchased. Searching online, I found fees to patients ranging from $42 to $100, with $65 being the most common. At $65 per test, the annual cost of screening about 230 million Americans 18 or older with ViziLite would be about $15 billion dollars! (The National Health Expenditure Accounts Projection Team estimates that the total expense for dental care in 2008 will be $102.4 billion [5].)

Cost-Effectiveness Not Established

Most screening tests are intended to separate people without symptoms who have a significant probability of having a disease from those who probably do not. To justify a screening test, the probable benefits must exceed the risks. To establish benefit, a test must lead to increased survival. Possible risks must include the cost of misdiagnosis as well as any physical risk associated with a test. Cost-effectiveness would also have to be demonstrated. Some oral cancers announce their presence with symptoms or are detectable by feeling the inside of the mouth with a finger. Thus to prove that ViziLite screening is worthwhile:

The early stages of some oral cancers are preceded by white or red patches on the gums, tongue, tonsil, or lining of the mouth that are visible to the naked eye. The key questions are (a) how often ViziLite examination would find patches not visible with the naked eye that, if found, would lead to increased survival, and (b) how often would false-positive cause unnecessary anxiety and expense for further testing. Once cancer develops, it is usually easy to spot without special lighting or staining. Some people get callous-like changes (leukoplakia) in the soft tissues of the mouth that can be precancerous. Most cases can be detected and followed using visual inspection.

The American Cancer Society (ACS) recommends that primary care doctors and dentists examine the mouth and throat as part of a routine cancer-related checkup. Although the cost of doing this as part of a physical exam is minimal, the U.S. Preventive Services Task Force (USPSTF) has concluded that "the evidence is insufficient to recommend for or against routinely screening adults for oral cancer." Its rationale:

. . . No new good-quality evidence that screening for oral cancer leads to improved health outcomes for either high-risk adults (i.e., those over the age of 50 who use tobacco) or for average-risk adults in the general population. It is unlikely that controlled trials of screening for oral cancer will ever be conducted in the general population because of the very low incidence of oral cancer in the United States. There is also no new evidence for the harms of screening. As a result, the USPSTF could not determine the balance between benefits and harms of screening for oral cancer [6].

The ACS and USPSTF statements are for screening for all types of oral cancer. Because ViziLite can detect only some of them, a higher standard would be required for validation. In 2005, the American Dental Association's Council on Scientific Affairs denied Zila's application for the ADA's Seal of Acceptance, saying that their submitted data were "extremely weak." [7]

Since that time, four studies have compared detection rates with ViziLite screening and screening with ordinary incandescent light and found no significant difference [8-11] and another study found modest benefit in evaluating patients known to have mucosal abnormalities or previously discovered cancer [12]. A Cochrane systematic review, published in 2006, evaluated screening programs for the early detection and prevention of oral cancer and concluded that (a) there is insufficient evidence to support or refute the use of screening in the general population, (b) systematic examination by dentists and physicians should still be routine, with particular attention paid to high-risk individuals, and (c) randomized controlled trials are needed to determine whether screening programs can detect oral cancer earlier and reduce the number of deaths from the disease [13]. In 2008, the American Academy of Oral and Maxillofacial Pathology issued a similar but more detailed position statement [14]. In 2010, the American Dental Association Council on Scientific Affairs concluded:

Two studies of ViziLite showed the device to have high sensitivity but low specificity when researchers confirmed its findings through histopathological examination. . . . Overall, visualization aids may affect a lesion's appearance in terms of brightness, texture and delineation of margins and in patients with previously detected lesions, but they have not been shown to enhance the practitioner's ability to identify potentially malignant lesions specifically or to identify lesions not visible under normal operatory lighting. Furthermore, there is insufficient evidence that these devices improve patient compliance or aid in patient education. . . . .

A visual examination cannot identify specifically the small proportion of lesions that exhibit early cancerous changes. Using currently available visualization aids does not allow a clinician to overcome this limitation. Clinicians should be aware that understanding the etiology of cancer along with the differences in clinical presentation of other similar abnormal ties remains of primary importance. Use of these devices can be associated with an increased risk of false-positive findings. The panel found insufficient evidence to make a recommendation for or against general dentists' use of these devices in their patients [15].

If studies could demonstrate that some lives are saved by oral screening, the question of cost would become important. It is estimated that in 2008, 35,310 Americans will be diagnosed with cancer of the oral cavity and pharynx and 7,590 will die from their disease [16]. If one case in 10 were saved by a ViziLite exam and the average increase in life were 10 years, the cost per year of life saved would be over $2 million. In contrast, breast cancer screening after age 65 is thought to cost $34,000 to $88,000 per year of life saved [17] and colon cancer screening is estimated to cost $10,000 to $25,000 per year of life saved [18]. Nobody knows how many adults ViziLite could help, but the number would probably be well under 10% of those who develop oral cancer. Regardless of the actual percentage, the cost per life saved would be far higher than that of medically accepted cancer screening methods. For patients at high risk for oral cancers, the cost per life saved would be lower, but would probably still be unacceptably high. In addition, false-positive tests would lead to unnecessary expense and patient anxiety. The ViziLite Web site contains success stories, but these are not substitutes for either benefit-risk or cost-effectiveness analysis.

In line with these facts, Aetna [19] and Cigna HealthCare [20] have issued policy statements which conclude that ViziLite is investigational or unproven and should therefore not be covered by their standard insurance programs. Zila states that some companies do cover the test, but I have not seen a list.

In 2013, the Canadian Agency for Drugs and Technologies in Health searched the literature and located 13 studies of ViziLite and two other light-based screening adjuncts, VELscope and Identafi. The reviewers concluded that "the available evidence does not support the use of the evaluated tools for the screening of cancer in the general population or those at low risk for malignancy." None of the studies measured cost-effectiveness [21].

The Bottom Line

ViziLite's promoters would like you to believe that the risk of getting oral cancer is high and that all adults should undergo annual screening with ViziLite Plus. The key question, however, is how often such screening will find precancerous changes in the mucous membranes not visible with the naked eye that, if found, would lead to increased survival. As far as I can tell, the answer is "not often enough to make the test worthwhile."

References

  1. Ulatowski TA. Letter to Martin L. Lonky re 510(k) No K012070, Nov 27, 2001.
  2. Zila acquires ViziLite™ - oral examination device. PR Newswire, Dec 5, 2001.
  3. Lin C. Letter to Martin L. Lonky re 510(k) No K033033, Jan 31, 2005.
  4. ViziLite Plus certification program. ViziLite Web site, accessed Sept 10, 2008.
  5. Screening for oral cancer. U.S. Preventive Services Task Force, 2004.
  6. Keehan S and others. Health spending projections through 2017: The baby-boom generation is coming to Medicare. Health Affairs 27:145-156, 2008.
  7. Murrah VA. Vizilite denied ADA seal of approval. Dentalblogs.com, Nov 10, 2005.
  8. Kerr AR and others. Clinical evaluation of chemiluminescent lighting: an adjunct for oral mucosal examinations. Journal of Clinical Dentistry 17:59-63, 2006.
  9. Oh ES, Laskin DM. Efficacy of the ViziLite system in the identification of oral lesions. Journal of Oral Maxillofacial Surgery 65:424-426, 2007.
  10. Farah CS, McCullough MJ. A pilot case control study on the efficacy of acetic acid wash and chemiluminescent illumination (ViziLite™) in the visualisation of oral mucosal white lesions. Oral Oncology 43:820-824, 2006.
  11. Epstein JB and others. The efficacy of oral lumenoscopy (ViziLite) in visualizing oral mucosal lesions. Special Care in Dentistry 26:171-174, 2006.
  12. Epstein JB and others. Analysis of oral lesion biopsies identified and evaluated by visual examination, chemiluminescence and toluidine blue. Oral Oncology 44:538-544, 2008.
  13. Kujan O and others. Screening programmes for the early detection and prevention of oral cancer. Cochrane Database of Systematic Reviews (3) CD004150, 2006.
  14. Lingen MW and others. Critical evaluation of diagnostic aids for the detection of oral cancer. Oral Oncology 44:10-22, 2008.
  15. ADA Council on Scientific Affairs Expert Panel on Screening for Oral Squamous Cell Carcinomas. Evidence-based clinical recommendations regarding screening for oral squamous cell carcinomas. Journal of the American Dental Association 141:509-20, 2010.
  16. SEER Stat fact sheet. Cancer of the oral cavity and pharynx, accessed Sept 8, 2008.
  17. Pignoni M and others. Systematic review: Cost-effective analyses of colorectal cancer screening. Annals of Internal Medicine 137:96-104, 2002.
  18. Mandelblat J and others. A systematic review The cost-effectiveness of screening mammography beyond age 65. Annals of Internal Medicine 139:835-842, 2003.
  19. Oral lesion identification systems. Aetna Clinical Policy Bulletin 0760, December 21, 2010..
  20. ViziLite and Veloscope oral screening systems. Cigna Healthcare coverage position, Oct 15, 2010.
  21. Screening for oral cancer using light-based techniques: A review of the diagnostic accuracy, cost-effectiveness, and guidelines. Canadian Agency for Drugs and Technologies in Health, Sept 10, 2013.

This article was revised on November 24, 2013.

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