Clinical UM Guideline


Subject: Testing for Oral and Esophageal Cancer
Guideline #: CG-LAB-12 Publish Date:    06/06/2018
Status: New Last Review Date:    05/03/2018


This document addresses the use of oral brush biopsies or esophageal brush biopsies for the detection of precancerous or cancerous lesions.

Clinical Indications

Not Medically Necessary:

Oral or esophageal brush biopsies for the diagnosis, screening, or surveillance of precancerous or cancerous lesions are considered not medically necessary.


The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.




Unlisted procedure, vestibule of mouth [when specified as a brush biopsy of oral mucosa]


Esophagoscopy, rigid, transoral; diagnostic, including collection of specimen(s) by brushing or washing when performed (separate procedure) [when specified as brush biopsy of esophagus]


Cytopathology, fluids, washings or brushings, except cervical or vaginal; smears with interpretation
Note: other pathology procedure codes for histology, when billed as part of analysis of a cytology brush biopsy, will be considered not medically necessary



ICD-10 Diagnosis



Barrett’s esophagus


Encounter for screening for malignant neoplasm of intestinal tract, unspecified


Encounter for screening for malignant neoplasm of oral cavity

Discussion/General Information

Oral Brush Biopsy

The oral brush biopsy, such as the OralCDx® Brush Biopsy (CDx Diagnostics, Suffern, NY), was developed as a painless screening method to evaluate oral lesions that could be precancerous or cancerous. The OralCDx system uses a specially-designed brush to collect cells from three layers of the epithelium. Once collected, the specimen is prepared and sent to a specialty laboratory for evaluation. If the specimen is suspected to be precancerous or cancerous, the lesion can then be removed by traditional scalpel biopsy, and the diagnosis can be confirmed by histology.

In 1999, Sciubba and colleagues conducted a large, double-blind, industry-supported, multicenter study on OralCDx. The investigators categorized 945 lesions as either Class I, suspicious lesions evaluated by both OralCDx and scalpel biopsy (n=298), or Class II, unsuspicious lesions evaluated only by OralCDx (n=647). OralCDx detected dysplasia or carcinoma in all lesions that were found abnormal by scalpel biopsy and histology (n=131). Of 196 lesions that were found negative by scalpel biopsy and histology, the OralCDx reported 182 as negative and 14 as atypical. The authors concluded that OralCDx has a sensitivity and specificity of 100% (92.9% for atypical results); however, the majority of lesions in the study were not directly compared to scalpel biopsy/histology thus rendering the data incomplete and making the results inconclusive. Additionally, the number of inadequate OralCDx samples was 7%. The authors noted that while OralCDx has potential value, it cannot replace traditional scalpel biopsy and histology.

Since the oral brush biopsy was introduced to the market in 1999, there have been a number of nonrandomized studies with varying results. In 2004, Poate and colleagues performed a retrospective analysis of 112 suspicious lesions and found that the OralCDx had a sensitivity of 71.4% (95% confidence interval [CI], 52.1% to 90.9%) and a specificity of 32% (95% CI, 14.8% to 49.4%). In a 2009 prospective study, Hohlweg-Majert and colleagues compared brush biopsy to synchronous histological biopsy in 75 suspicious lesions. The sensitivity rate for OralCDx was 52% with a specificity of 29% (CI not reported). In a 2011 study, Mehrotra and colleagues performed a prospective study in which 79 minimally suspicious lesions were tested with OralCDx immediately followed by scalpel biopsy. The authors found that OralCDx had a sensitivity of 96.3% (95% CI, 87% to 100%) and a specificity of 100% (95% CI, 93% to 100%).

In a 2013 Cochrane Review, Brocklehurst and colleagues evaluated oral cancer screening methods. They noted a lack of randomized controlled trials and a high risk of bias in the available studies. In addition, they stated that there was not enough evidence to support a general screening for oral cancer. The authors concluded that there is no evidence that adjunct technology, including brush biopsy, decreases oral cancer mortality. Likewise, in a 2015 Cochrane Review, Macey and colleagues evaluated the accuracy of index tests, including oral cytology brush biopsies, for detecting oral cancer. They also noted a lack of high-quality studies available. The authors concluded that no adjunctive test can be recommended as a replacement for scalpel biopsy and histological assessment.

Alsarraf and colleagues (2018) performed a systematic review on the utility of oral brush cytology compared to scalpel biopsy for the early detection of oral malignancy. They included 36 peer-reviewed studies (4302 samples) that included liquid-based cytology (LBC) or exfoliative cytology. The most commonly used oral brushes were a cytobrush (LBC or exfoliative cytology), the OralCDx brush (conventional exfoliative cytology), the Orcellex® brush (LBC; Netherlands), and a baby toothbrush (LBC or conventional exfoliative cytology; India). For the OralCDx brush, the authors found that several studies reported a wide range of sensitivity (71% - 100 %, or not reported) and specificity (32% - 100%, or not reported). Many studies had heterogeneous sampling techniques and lacked validated protocols for evaluation and surveillance. The authors concluded that LBC brush biopsies, possibly with molecular testing, have more advantages than exfoliative cytology. However, they recommended well-designed, longitudinal studies with clear criteria and accurate cyto-histopathological correlation.

Currently, there is a lack of well-designed, prospective studies demonstrating the clinical validity and clinical utility of oral brush biopsies.

Other Considerations for Oral Brush Biopsy

In a 2013 statement on screening for oral cancer, the U.S. Preventive Services Task Force (USPSTF) stated that “screening and adjunct tests have not been adequately tested in primary care nondental settings,” and that “the current evidence is insufficient to assess the balance of benefits and harms of screening for oral cancer in asymptomatic adults.”

In a 2017 Physician Data Query (PDQ) on oral cavity and oropharyngeal cancer screening, the National Cancer Institute (NCI) stated that adjunctive screening methods “have not been shown to have superior sensitivity and specificity for visual examination alone or to yield better health outcomes.” They also note that screening for oral cancer can lead to the following:

Esophageal Brush Biopsy

An esophageal brush biopsy, such as the WATS3D® System (CDx Diagnostics, Suffern, NY), has been proposed as an adjunct to traditional four-quadrant forceps biopsy for screening and surveillance of individuals with Barrett’s esophagus (BE). The WATS3D system uses a specialized brush that attaches to an endoscope and collects a wide area, transepithelial specimen of the full-thickness esophageal mucosa. The sample is prepared and sent to a specialty laboratory where it is analyzed by specially-trained pathologists using three-dimensional software. The adjunct esophageal brush biopsy proposes to increase the size of the biopsy sample, thereby potentially increasing accuracy in the diagnosis of precancerous or cancerous esophageal disease.

The WATS3D system was formerly known as EndoCDx®. In a multicenter, industry-supported trial, Johanson and colleagues (2011) compared forceps biopsy to EndoCDx esophageal brush biopsy for 1266 subjects who were being screened for BE. The authors found that brush biopsy increased the detection of BE by 39.8% (95% CI, 32% to 48%). A total of 139 subjects were found to have BE by brush biopsy that were not found by forceps biopsy; however, 166 subjects were found to have BE only with forceps biopsy. Likewise, brush biopsy revealed 14 subjects with dysplasia not found by forceps biopsy, but forceps biopsy found 11 subjects with dysplasia not found with brush biopsy. The authors concluded that the adjunctive use of brush biopsy improves detection of BE and dysplasia in a screening population.

In an industry-supported study evaluating EndoCDx, Anandasabapathy and colleagues (2011) compared forceps and EndoCDx brush biopsies in 151 subjects with a known history of BE and dysplasia. The brush biopsy was able to detect dysplasia of any kind (that is, low grade dysplasia, high grade dysplasia or carcinoma) in 16 subjects not found by forceps biopsy alone, reporting a number needed to treat (NNT) of 9.4 (95% CI, 5.6 to 16.6). Forceps biopsy found 23 cases of dysplasia not found by brush biopsy. The authors concluded that esophageal brush biopsy may be a valuable adjunct for high-risk subjects with Barrett’s esophagus.

In a prospective, randomized, multicenter, industry-supported study, Vennalaganti and colleagues (2017) compared WATS3D  brush biopsy to forceps biopsy in 160 subjects with BE. Subjects either received forceps biopsy followed by WATS3D or WATS3D followed by forceps biopsy. WATS3D detected 23 cases of high-grade dysplasia/esophageal adenocarcinoma (HGD/EAC) not found initially with forceps biopsy (absolute increase 14.4%; 95% CI, 7.5% to 21.2%). Among these 23 patients, 11 were classified by biopsy as non-dysplastic BE, and 12 as low grade dysplasia/indeterminate; the majority (n=21; 91.7%) had a prior dysplasia history. Subsequent follow-up was available for 9 of the 23 WATS3D classified HGD/EAC patients: 2 had HGD, 2 had EAC, 3 had LGD and 2 had no dysplasia. WATS3D missed one case of HGD/EAC found by forceps biopsy. The authors noted that the study may not be generalizable to a low-risk BE surveillance population. The authors concluded that WATS3D increased the detection of HGD/EAC in a high-risk surveillance population and “may be a useful addition to standard endoscopic surveillance programs for the diagnosis of BE neoplasia.”

Because there are no peer-reviewed, published studies available that directly compare WATS3D to traditional biopsy, the validity of the test cannot be confirmed. In addition, the available studies contain limited follow-up data to confirm the determination made by WATS3D and to assess long-term outcomes. Further, well-designed studies are needed to assess the clinical validity and clinical utility of WATS3D.

Other Considerations for Esophageal Brush Biopsy

According to a guideline (Shaheen, 2016) on the diagnosis and management of Barrett’s esophagus by the American College of Gastroenterology (ACG):

The addition of routine cytologic sampling to endoscopic biopsies appears to add little to surveillance biopsies. The role of computer-assisted or wide-field “brush biopsy” tissue acquisition for increasing the yield of dysplasia is currently under investigation. Currently, the finding of subsquamous BE on surveillance biopsies of the untreated patient does not change patient management, based on the most advanced histology found on the combination of targeted and random biopsies.

In a 2017 PDQ on Esophageal Cancer Screening, the NCI stated, “Based on fair evidence, screening would result in no (or minimal) decrease in mortality from esophageal cancer in the U.S. population.”



Barrett’s Esophagus: a condition in which the lining of the esophagus is damaged by stomach acid. People with BE have an increased risk for cancer in the area involved. However, cancer is not common.



Peer Reviewed Publications:

  1. Alsarraf A, Kujan O, Farah CS. The utility of oral brush cytology in the early detection of oral cancer and oral potentially malignant disorders: A systematic review. J Oral Pathol Med. 2018; 47(2):104-116.
  2. Anandasabapathy S, Sontag S, Graham DY, et al. Computer-assisted brush-biopsy analysis for the detection of dysplasia in a high-risk Barrett's esophagus surveillance population. Dig Dis Sci. 2011; 56(3):761-766.
  3. Hohlweg-Majert B, Deppe H, Metzger MC, et al. Sensitivity and specificity of oral brush biopsy. Cancer Invest. 2009; 27(3):293-297.
  4. Johanson JF, Frakes J, Eisen D. Computer-assisted analysis of abrasive transepithelial brush biopsies increases the effectiveness of esophageal screening: a multicenter prospective clinical trial by the EndoCDx Collaborative Group. Dig Dis Sci. 2011; 56(3):767-772.
  5. Mehrotra R, Mishra S, Singh M, Singh M. The efficacy of oral brush biopsy with computer-assisted analysis in identifying precancerous and cancerous lesions. Head Neck Oncol. 2011; 3:39.
  6. Poate TW, Buchanan JA, Hodgson TA, et al. An audit of the efficacy of the oral brush biopsy technique in a specialist oral medicine unit. Oral Oncol. 2004; 40(8):829-834.
  7. Sciubba JJ. Improving detection of precancerous and cancerous oral lesions. computer-assisted analysis of the oral brush biopsy. U.S. Collaborative OralCDx Study Group. J Am Dent Assoc. 1999; 130(10):1445-1457.
  8. Vennalaganti PR, Kaul V, Wang KK, et al. Increased detection of Barrett's esophagus-associated neoplasia using wide-area trans-epithelial sampling: a multicenter, prospective, randomized trial. Gastrointest Endosc. 2017; 87(2):348-355.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Brocklehurst P, Kujan O, O'Malley LA, et al. Screening programmes for the early detection and prevention of oral cancer. Cochrane Database Syst Rev. 2013; 19;(11):CD004150.
  2. Macey R, Walsh T, Brocklehurst P, et al. Diagnostic tests for oral cancer and potentially malignant disorders in patients presenting with clinically evident lesions. 2015; 29;(5):CD010276.
  3. National Cancer Institute. Esophageal Cancer Screening (PDQ®)–Health Professional Version. Bethesda, MD. 2018 April. Available at: Accessed on April 11, 2018.
  4. National Cancer Institute. Oral Cavity and Oropharyngeal Cancer Screening (PDQ®)–Health Professional Version. Bethesda, MD. 2018 March. Available at: Accessed on April 11, 2018.
  5. Shaheen NJ, Falk GW, Iyer PG, Gerson LB. Corrigendum: ACG Clinical Guideline: Diagnosis and Management of Barrett's Esophagus. Am J Gastroenterol. 2016; 111(7):1077.
  6. U.S. Preventive Services Task Force. Final update summary: oral cancer: screening. 2013 November. Available at: Accessed on April 11, 2018.
Websites for Additional Information
  1. American Cancer Society. Can esophageal cancer be found early? Last revised June 14, 2017. Available at: Accessed on April 11, 2018.
  2. American Cancer Society. Can oral cavity and oropharyngeal cancers be found early? Last revised March 9, 2018. Available at: Accessed on April 11, 2018.

Esophageal Brush Biopsy
Oral Brush Biopsy

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Medical Policy & Technology Assessment Committee (MPTAC) review.



Hematology/Oncology Subcommittee review. Initial document development.