Director's Note: The lead story in the July issue of the Journal of the American Dental Association, deals with adjunctive techniques in the screening and detection of oral cancer lesions. As clinicians, we should creatively think about each research article that emerges and learn how to apply the information to our own practice each day. Peter Vanstron, DDS, Atlanta, Ga., presents his view of the "systematic review" so we can further understand our responsibility utilizing the best practices in the field on oral cancer adjuncts.
Cover Story: JADA (July 2008)
"Adjunctive Techniques for Oral Cancer Examination and Lesion Diagnosis — A Systematic Review of the Literature
Authors: Lauren L. Patton, DDS, FDS, RCSEd, Joel Epstein, DMD, MSD, FRCD(C), A. Ross Kerr, DDS,MSD
Overview: This article is a review of selected literature pertaining to adjunctive techniques, including visualization adjuncts (VLP, VEL, MicroLux DL/Orascoptic DK)and diagnostic adjuncts (TBlue, Oral CDx/Brushtest). The authors of this article ONLY considered those clinical studies that have biopsies and associated histologic diagnoses as part of the study criteria. Because of these criteria, all of the adjuncts being evaluated are treated as oral cancer diagnostic adjuncts, not oral cancer screening adjuncts.
• The National Cancer Institute (NCI) defines cancer screening as the detection of disease early in asymptomatic people. The NCI also states that positive results of cancer screening exams are usually not being diagnostic but identify persons at increased risk of the presence of cancer who warrant further evaluation, www.cancer.gov. ViziLite Plus with TBlue is an adjunctive cancer screening technology, combining the high sensitivity ideal in a cancer screening system, with the vital staining of TBlue, proven to reduce false positive results, high specificity and no false negative results.
Key Points of the Review:
1. Limited literature selection: A total of 8 papers have been published concerning the efficacy of ViziLite and/or ViziLite Plus. Based on the limited literature selection criteria (requiring histologic diagnoses), only 2 were included in this review. Therefore, only 2 articles comprise the basis for the authors' opinions of ViziLite. The authors correctly stated that ViziLite alone is no longer available; ViziLite is only available as part of the ViziLite Plus with TBlue oral cancer screening system. The following published papers documenting the efficacy of VL in its ability to improve the ability to see lesions and to detect lesions missed during conventional visual examination were not included in the clinical review:
a. Huber MA, Bsoul SA, Terezhalmy GT. Acetic acid wash and chemiluminescent illumination as an adjunct to conventional oral soft tissue examination for the detection of dysplasia: a pilot study. Quintessence Int. 2004 May;35(5):378-84.
b. Kerr AR, Sirois DA, Epstein JB. Clinical evaluation of chemiluminescent lighting: an adjunct for oral mucosal examinations. J Clin Dent. 2006;17(3):59-63.
c. Epstein JB et al. The efficacy of oral lumenoscopy (ViziLite) in visualizing oral mucosal lesions. Spec Care Dentist. 2006 Jul-Aug;26(4):171-4.
• One of the JADA review's authors, Dr. Ross Kerr (a specialist in Oral Medicine), was the lead author in a ViziLite study published in The Journal of Clinical Dentistry. In this study of 501 patients performed at NYU (his institution), 6 lesions suspicious for pathology were detected with ViziLite that went undetected by conventional visual examination. This study was not included in the review because no histopathology is associated with the study.
• Another of the JADA review's authors, Dr. Joel Epstein, was the lead author in a ViziLite study published in Special Care Dentistry. In this multi-center study of 134 patients, 2 clinically suspicious lesions found by ViziLite were missed during the investigators' conventional exam. One of the lesions was determined upon scalpel biopsy to be a recurrent squamous cell carcinoma
• The Huber study, was a general screening trial in which 150 consecutive patients, age 19 to 70, were initially screened by conventional exam and then under ViziLite illumination. 1 clinically suspicious lesion was identified by ViziLite that was missed by the examiners' conventional examination. The lesion was located on the floor of the mouth and proved to be mild dysplasia
2. Literature review of detection technologies:
a. Visualization adjuncts (ViziLite , VELscope, MicroLux DL/Orascoptic DK)
• ViziLite (no longer available without TBlue) — Sensitivity of 100%; improved visualization of 60% of lesions. "The addition of TB application to the chemiluminescence-enhanced visual examination in the multi-center study improved the specificity and PPV and increased the NPV to 100 percent". TBlue also reduced false positive results by 55%.
• VELscope — no clinical studies supporting efficacy as an adjunctive screening technology. Quote from review" both studies of the VELscope technology were conducted at the same center in patients with known oral dysplasia or SCC confirmed by biopsy and did not involve the use of the technology as an adjunct for detection or diagnosis of new lesion." And they protocol used TBlue to determine what went out for biopsy.
• Microlux DL/Orascoptic DK — No clinical data/no review.
• Cytopathology (Oral CDx/Brushtest) — Not a technique to improve detection. It's useful in the assessment of dysplastic changes in clinically suspicious lesions; however, there are insufficient data meeting the inclusion criteria to assess usefulness in innocuous mucosal lesion. Inconsistencies in specificities.
• Vital tissue staining (TBlue, only available with ViziLite Plus with TBlue) — Lots of clinical data supporting its efficacy as a diagnostic adjunct. High sensitivity (93.5%) and high specificity (73.3%). Cited BC study that demonstrated that even lesions with little or no dysplasia were strongly predictive of risk of malignant transformation. Important quote from review, "it appears that any staining should evaluate the clinical suspicion, and instense staining may be even more sensitive". Also another important quote from review: "Although a 1 percent TB solution can be prepared from nonpharmaceutical (laboratory) -grade TB, the pharmaceutical-grade TB (which meets higher standards) is available in the United States only as part of the combination ViziLite Plus with TBlue kit." Additionally, generic toluidine blue is not approved for human use.
• The primary takeaway for ViziLite, although mentioned once, is the sensitivity is 100%. ViziLite examination detects EVERY pathological lesion. ViziLite doesn't diagnose, it finds it. Additionally, improvement in visualization parameters (among specialists) of more than 60%. Combines adjunct visual exam (high sensitivity) with diagnostic adjunct (high specificity/reducing false positives by 55% and unnecessary biopsies).
• The authors recognize the BC Cancer Agency study is important in the identification of lesions exhibiting genetic alterations that precede phenotypic (clinical) change. The study used Zila's tolonium chloride (TBlue) to identify such lesions. In this study premalignant lesions that retained the TB dye had a 600% increased probability of malignant transformation.
i. The BC Cancer Agency standard protocol includes the staining of ALL lesions with toluidine blue. Why? Because of TBlue's proven ability to reduce false positives.
2. Positive Lesion Protocol — The authors stressed the importance of the 7-14 waiting period as a means of reducing false positive results.
• This is a critical part of the ViziLite Plus with TBlue training program that is emphasized in all of our training.
3. Relative Oral Cancer Risk Profile — The authors of the review fail to mention the increasing role of HPV in 22% of oral cancers particularly affecting the younger patient population. The authors talk about screening the "high risk" population. What about Grant Achatz and the 22% of oral cancer cases attributed to HPV, particularly in the patient population younger than 40? What about the 10% of oral cancer victims who are younger than age 40?
4. Age — Age is the primary risk factor for most cancers, and it's no different with oral cancer. Adjunctive cancer screening technologies are used when patients are at increased risk for cancer, when approximately 5-10% of victims are diagnosed with a given cancer, not when victims are at high risk for the cancer. That is why the age for adjunctive cancer screening for other cancers is as follows (per MayoClinic.com):
• Cervical cancer: 18&high risk age 30-35; highest risk age 50; 50% of cervical CA cases occur in women age 35-50
• Breast cancer (no family history): 40; high risk age 50+ (80% of cases)
• Prostate cancer : 45/50; high risk age 60
• Oral cancer: 18 (10% of victims younger than age 40); high risk age 40+; tobacco use
5. Dismal results of the conventional visual exam — The authors fail to mention that the incidence and survival rates for oral cancer have remained unchanged for 40 years with the conventional exam alone. They failed to mention that 70% of oral cancer lesions detected with the visual exam alone are detected in stages III and IV when the 5-year survival rate is less than 60%. The authors fail to mention that more than 85% of oral premalignant lesions and oral cancer are leukoplakic lesions. These lesions are very difficult to detect with the unaided eye alone, especially by non-specialists who are seeing the bulk of these patients. The authors failed to present one paper on the efficacy of the conventional visual examination. In a prior clinical review in the Journal of Oral Oncology, authors cited 3 references at the lack of effectiveness of the visual exam alone at detecting premalignant lesions and early stage cancer, and the fact that effectiveness of the visual exam alone is "controversial".
Conclusion: ViziLite Plus with TBlue is not a perfect adjunctive screening and diagnostic technology; neither are the Pap smear, mammogram and PSA test. However, ViziLite Plus with TBlue, following the conventional exam, has been proven in multiple studies as a better method of detecting potentially suspicious lesions than the visual exam alone, with a sensitivity of 100%, improving visualization of 60% of lesions. The authors recommended TBlue as a diagnostic adjunct in assessing high risk mucosal lesions. The clinically proven combination of improved visualization and detection of suspicious lesions with VL (the light aids your sight) followed by the application of TBlue to clinically suspicious lesions (the dye doesn't lie) provides health professionals with the most effective oral cancer adjunctive screening and diagnostic system available today.