Currentblue cross blue shield - tennesseePolicy N/A

Oral Cancer Screening and Testing — Coverage Criteria

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Governs coverage for diagnostic testing and adjunctive screening methods for oral and oropharyngeal cancer for Blue Cross Blue Shield - Tennessee members; defines what tests meet or do not meet coverage criteria.

Policy Summary

Payerblue cross blue shield - tennessee

PolicyOral Cancer Screening and Testing — Coverage Criteria

Policy CodePolicy N/A

Change TypeNo material change noted

Effective DateN/A

Next Review DateN/A

Key ActionFor oropharyngeal squamous cell carcinoma, document and perform HPV testing using either HPV E6/E7 mRNA expression testing or p16 immunohistochemistry to support coverage.

SourceLink

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Currentblue cross blue shield - tennesseePolicy N/A

Oral Cancer Screening and Testing — Coverage Criteria

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Sign up for all blue cross blue shield - tennessee policy alerts

Know when blue cross blue shield - tennessee releases new policies or updates existing guidance.

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Policy Summary

Payerblue cross blue shield - tennessee

PolicyOral Cancer Screening and Testing — Coverage Criteria

Policy CodePolicy N/A

Change TypeNo material change noted

Effective DateN/A

Next Review DateN/A

Key ActionFor oropharyngeal squamous cell carcinoma, document and perform HPV testing using either HPV E6/E7 mRNA expression testing or p16 immunohistochemistry to support coverage.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

54,540estimated US diagnoses in 2023

11,580estimated US deaths in 2023

p16 / HPV E6/E7tests that meet coverage for oropharyngeal SCC

InsufficientUSPSTF screening stance

51HPV genotypes (OraRisk)

Coverage Criteria

inv-01: HPV testing for oropharyngeal squamous cell carcinoma

Covered when ANY of the following test methods are used for individuals with oropharyngeal squamous cell carcinoma:

Covered HPV tests: mRNA expression testing for HPV E6/E7 OR immunohistochemistry for p16 expression

These tests MEET COVERAGE CRITERIA for oropharyngeal squamous cell carcinoma as stated in the policy.

inv-02: Not covered for screening, detection, or diagnosis of oral cancer

The following tests do NOT meet coverage criteria due to insufficient published evidence of clinical benefit:

Excluded adjunctive tests: Salivary biomarker testing (e.g., peptides/proteins, nucleic acids, metabolites); Genotyping of HPV (e.g., OraRisk® HPV); Gene expression profiling; Panels that incorporate genetic risk factors with nongenetic biomarkers (e.g., mRNA CancerDetect™)

Explicitly listed as not meeting coverage for screening, detection, or diagnosis of oral cancer.

inv-03: HPV testing (p16 IHC) — recommended

Coverage and clinical testing expectations reflected from guideline positions and evidence statements:

HPV/p16 testing for oropharyngeal SCC: p16 immunohistochemistry is recommended as a surrogate for high-risk HPV status and should be performed for newly diagnosed oropharyngeal squamous cell carcinomas and in squamous cell carcinoma of unknown primary per guideline panels (NCCN, CAP, ASCO, EHNS/ESMO/ESTRO).

p16 IHC has very good agreement with HPV E6/E7 mRNA expression and is widely endorsed by guideline organizations.

inv-04: Adjunctive devices and salivary assays — investigational/limited

Adjunctive screening aids and salivary biomarker assays — evidence summary and screening recommendations:

Adjunctive light-based devices and salivary biomarkers: Light-based detection systems, autofluorescence/tissue-reflectance adjunctive devices, and salivary biomarker assays may assist with lesion assessment, margin delineation, and biomarker development, but current evidence is insufficient to support routine screening of asymptomatic adults and guideline bodies do not endorse autofluorescence/tissue reflectance devices as primary management tools.

USPSTF (2013) concluded evidence insufficient for screening; systematic reviews and guideline statements note limited evidence for routine use.

Salivary biomarker assays, HPV genotyping (for example, OraRisk® HPV), gene expression profiling, and multi‑marker panels that combine genetic and nongenetic biomarkers are specifically listed in this policy as tests that do not meet coverage criteria when used to screen, detect, or diagnose oral cancer. By contrast, for individuals with diagnosed oropharyngeal squamous cell carcinoma, testing for high‑risk HPV using either mRNA expression testing for HPV E6/E7 or p16 immunohistochemistry (IHC) is identified as meeting coverage criteria and is the recommended approach for establishing HPV status in that clinical context.

The US Preventive Services Task Force (USPSTF) in 2013 concluded that the evidence is insufficient to assess the balance of benefits and harms for screening for oral cancer in asymptomatic adults. The USPSTF statement also notes that, despite interest in screening for oral HPV infection, professional medical and dental organizations do not recommend routine screening for oral HPV in asymptomatic populations.

The references section of the policy lists bibliographic citations (systematic reviews, guideline documents, and primary studies) relevant to oral cancer screening, adjunctive detection methods, salivary diagnostics, and HPV testing. This block provides citation notes and does not itself state coverage exclusions or medical‑necessity determinations; those determinations appear elsewhere in the policy text.

Per the policy language, use of the tests enumerated in the exclusions list—including salivary biomarker testing, HPV genotyping (e.g., OraRisk® HPV), gene expression profiling, and panels that combine genetic and nongenetic biomarkers—to screen, detect, or diagnose oral cancer is considered not covered due to insufficient published evidence demonstrating clinical benefit.

The National Comprehensive Cancer Network (NCCN) head and neck cancers guideline does not list adjunctive screening aids based on autofluorescence or tissue reflectance as a management tool; systematic reviews and guideline citations included in the references indicate these light‑based and reflectance devices have limited evidence for routine screening and are not endorsed as primary management modalities.

Although the bibliography cites guideline statements, systematic reviews, and vendor materials, the citation lists themselves do not contain explicit independent not medically necessary determinations; coverage and medical‑necessity conclusions are set forth in the policy's coverage criteria and exclusion sections.

Coding and Billing

OraRisk HPV — Genotype listing (by risk category)mixed

High-risk genotypes	16, 18, 26, 30, 31, 33, 34, 35, 39, 45, 51, 52, 53, 56, 58, 59, 64, 66, 67, 68, 69, 70, 73, 82
Low-risk genotypes	2a, 6, 11, 32, 40, 42, 43, 44, 54, 55, 57, 61, 62, 71, 72, 74, 77, 81, 83, 84, 89
Unknown-risk genotypes	41, 49, 60, 75, 76, 80, 85

Applicable CPT/HCPCS and other procedure codesmixed

81599	Unlisted multianalyte assay with algorithmic analysis
82397	Chemiluminescent assay
87623	Infectious agent detection by nucleic acid (DNA or RNA); Human Papillomavirus (HPV), low-risk types (e.g., 6, 11, 42, 43, 44)
87624	Infectious agent detection by nucleic acid (DNA or RNA); Human Papillomavirus (HPV), high-risk types (e.g., 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68)
87625	Infectious agent detection by nucleic acid (DNA or RNA); Human Papillomavirus (HPV), types 16 and 18 only, includes type 45, if performed
88341	Immunohistochemistry or immunocytochemistry, per specimen; each additional single antibody stain procedure
88342	Immunohistochemistry or immunocytochemistry, per specimen; initial single antibody stain procedure
0296U	Oncology (oral and/or oropharyngeal cancer), gene expression profiling by RNA sequencing at least 20 molecular features (e.g., human and/or microbial mRNA)

Provider Actions and Administrative Rules

Billing Rule

Proprietary assay coding

Certain proprietary multianalyte assays and manufacturer-specific tests are cited in this policy and listed in the procedure code section. When billing or requesting coverage, providers should verify coding and any payer-specific guidance for these proprietary assays (for example, mRNA CancerDetect™ / Viome Life Sciences, Inc. and other tests mapped to codes such as 0296U or 81599). Use the listed CPT/HCPCS codes only as general references and confirm appropriate unlisted or proprietary-code reporting and submission requirements with the payer prior to claim submission.

Examples: 0296U (mRNA CancerDetect™), 81599 (unlisted multianalyte assay with algorithmic analysis)
Procedure codes in policy are for reference; confirm payer-specific billing guidance

Denial Risk

Background

Oral cancer most commonly presents as squamous cell carcinoma and is frequently preceded by potentially malignant disorders such as erythroplakia and leukoplakia. Human papillomavirus plays a role in oropharyngeal cancers; guideline panels and the policy identify p16 IHC and HPV E6/E7 mRNA expression testing as accepted methods to determine high‑risk HPV status in oropharyngeal squamous cell carcinoma. Adjunctive techniques—including vital staining, light‑based detection systems, brush cytology, and salivary biomarker assays—may assist in lesion assessment or biomarker development but are not substitutes for conventional oral examination and histopathologic diagnosis by biopsy.

Definitions

Oral cancer / oral cavity definition

Anatomical boundariesCancer occurring in the oral cavity between the vermilion border of the lips and the junction of the hard and soft palates or the posterior one third of the tongue.

Common histologySquamous cell carcinoma is the most common type of oral cancer.

ScopeIncludes lesions of the oral cavity (lips to hard/soft palate junction and posterior one-third of tongue).

HPV / p16 / IHC

HPV termHuman papillomavirus (HPV).

p16 IHC rolep16 detected by immunohistochemistry (IHC) serves as a surrogate biomarker for high-risk HPV with very good agreement with HPV E6/E7 mRNA expression.

Revision History

2023-12-20guideline citation updateLatest

NCCN Clinical Practice Guidelines in Oncology — Head and Neck Cancers (Version 1.2023) cited in references.

2020vendor resource added

OraRisk® HPV (OralDNA) test reference added to bibliographic references.

2020vendor resource added

Policy Summary

Payerblue cross blue shield - tennessee

PolicyOral Cancer Screening and Testing — Coverage Criteria

Policy CodePolicy N/A

Change TypeNo material change noted

Effective DateN/A

Next Review DateN/A

Key ActionFor oropharyngeal squamous cell carcinoma, document and perform HPV testing using either HPV E6/E7 mRNA expression testing or p16 immunohistochemistry to support coverage.

SourceLink

On This Page

Denied adjunctive tests for screening/diagnosis

Coverage will be denied for adjunctive tests used to screen, detect, or diagnose oral cancer when there is insufficient evidence of clinical benefit. Specifically, salivary biomarker testing, HPV genotyping assays (e.g., OraRisk® HPV), gene expression profiling, and panels combining genetic and nongenetic biomarkers (e.g., mRNA CancerDetect™) DO NOT MEET COVERAGE CRITERIA for screening, detection, or diagnosis of oral cancer.

Salivary biomarker testing (peptides/proteins, nucleic acids, metabolites) — not covered
HPV genotyping (e.g., OraRisk® HPV) — not covered
Gene expression profiling — not covered
Panels combining genetic and nongenetic biomarkers (e.g., mRNA CancerDetect™) — not covered

Note

Conflict with Government Policy

If there is a conflict between this policy and any applicable government policy (for example, Medicare Local Coverage Determinations or National Coverage Determinations, or state Medicaid policies), the government policy will supersede and be used to make coverage determinations for members covered by those programs. Providers should consult CMS and relevant state Medicaid resources for the most current guidance.

Follow Medicare/Medicaid LCDs/NCDs or state Medicaid policy when in conflict with this policy
CMS Medicare Coverage Database: https://www.cms.gov/medicarecoverage-database/search.aspx

Prior Authorization

No authorization or denial criteria specified in citations

The cited references and procedure code list do not include explicit prior authorization, approval, or denial criteria. Providers must follow the member's benefit plan and payer administrative rules for prior authorization or precertification where applicable and verify any payer-specific authorization requirements before ordering proprietary or high-cost tests.

No prior authorization rules specified in this policy section — check member benefits
Procedure codes included as general reference and may not be all-inclusive

Documentation Required

LDT validation and CLIA

Laboratory-developed tests (LDTs) referenced in this policy are regulated under CLIA as high-complexity tests and must be validated and performed in-house by the performing laboratory. Documentation of CLIA status and internal validation should be available upon request to support clinical use, since LDTs are not FDA-approved or -cleared.

LDTs are regulated by CMS as high-complexity CLIA tests
LDTs require laboratory validation and should be performed in-house
FDA clearance/approval is not required for clinical use but LDT validation documentation may be requested

Documentation Required

No documentation requirements are specified

The policy citations and bibliography do not specify detailed documentation requirements for coverage determinations beyond standard clinical documentation. Providers should supply relevant clinical records, pathology reports (including method of HPV testing such as mRNA E6/E7 expression or p16 IHC for oropharyngeal squamous cell carcinoma), and any laboratory validation information for LDTs when requested by the payer to support medical necessity.

For oropharyngeal squamous cell carcinoma, document HPV testing method (mRNA E6/E7 expression or p16 IHC)
Provide clinical notes, pathology reports, and LDT validation/CLIA documentation upon payer request
Policy references do not prescribe a separate documentation checklist

Step Therapy

No step therapy rules described

No step therapy rules or quantity limits are described in the cited policy sections. If the payer has step therapy or utilization management programs that could affect test access, providers should consult the member's benefit plan or contact the payer for operational requirements prior to ordering.

Policy contains no step therapy rules for diagnostic testing
Verify any plan-level step therapy or utilization management programs separately

Note

(Placeholder retained for completeness)

Clinical usep16 IHC is widely available and used in the diagnostic workup to indicate HPV-associated tumors.

p16 IHC — guideline endorsements

Surrogate markerp16 immunohistochemistry is a surrogate immunohistochemical marker for high‑risk HPV status in oropharyngeal carcinomas.

Guideline endorsementsRecommended and required by guideline panels including NCCN and CAP for oropharyngeal tissue specimens; endorsed by expert panels (ASCO) per guideline statements.

Clinical expectationp16 IHC should be performed for newly diagnosed oropharyngeal SCC and in SCC of unknown primary as part of workup.

Laboratory‑developed test (LDT)

DefinitionLaboratory‑developed test (LDT): an in‑house developed assay that laboratories validate and perform internally.

RegulationLDTs are regulated by CMS as high‑complexity tests under CLIA '88.

FDA statusLDTs are not approved or cleared by the U.S. Food and Drug Administration; FDA clearance/approval is not currently required for clinical use.

OraRisk (OralDNA) tests

Vendor / brandOraRisk® (OralDNA).

Test identifiersOraRisk® HPV 16/18/HR and OraRisk® HPV Complete Genotyping.

SourceProduct pages cited: OralDNA (2020) OraRisk® HPV 16/18/HR; OralDNA (2023) OraRisk® HPV Complete Genotyping.

SaliMark (PeriRx)

Vendor / brandSaliMark™ (PeriRx).

Test identifierSaliMark™ OSCC: Oral Cancer Salivary Diagnostic Test.

SourcePeriRx (2020) SaliMark™ OSCC product citation in references.

SaliMark™ OSCC (PeriRx) salivary diagnostic test referenced in the bibliography.

2016systematic review cited

Systematic review on efficacy of light-based detection systems for oral cancer (Nagi et al.) added to references.

2010evidence-based recommendation cited

Evidence-based clinical recommendations regarding screening for oral squamous cell carcinomas (Meyer DM et al., J Am Dent Assoc 2010) included in references.

2000foundational reference cited

ABC of oral health — Oral cancer (Scully & Porter, 2000) included in bibliography.