Currentblue cross blue shield - tennesseePolicy N/A

Oral Cancer Screening and Testing

Defines coverage stance for tests used to establish HPV tumor status in oropharyngeal squamous cell carcinoma and exclusions for various oral cancer screening tests (salivary biomarkers, genotyping, gene expression panels, etc.), and lists applicable CPT/HCPCS/Proprietary procedure codes. Applies to BlueCross BlueShield of Tennessee members, subject to individual benefit coverage and federal/state regulations.

Policy Summary

Payerblue cross blue shield - tennessee

PolicyOral Cancer Screening and Testing

Policy CodePolicy N/A

Change TypeNo material changes

Effective Date

Next Review Date

Key ActionProviders must document that the individual has oropharyngeal squamous cell carcinoma when ordering testing to establish HPV tumor status (p16 IHC or HPV E6/E7 mRNA testing).

POLICY UPDATE CHANGES

No material clinical/coverage changes

1Covered Indication (HPV testing for OPSCC)

4Not covered test categories (listed)

9Procedure codes referenced

Coverage Summary

Scope: Defines coverage stance for tests used to establish HPV tumor status in oropharyngeal squamous cell carcinoma (OPSCC) and exclusions for various oral cancer screening tests (salivary biomarkers, genotyping, gene expression panels). Lists applicable CPT/HCPCS/Proprietary procedure codes and notes application is subject to individual benefit coverage and federal/state regulations.

Coverage stance: Mixed — HPV testing to determine tumor status in individuals with confirmed OPSCC is covered when criteria are met, while salivary biomarker tests, HPV genotyping assays, and gene expression profiling panels (e.g., mRNA CancerDetect™) are identified as not meeting coverage criteria.

Coding

Covered / Relevant procedure codes (reference list)mixed

82397	Chemiluminescent assay
87624	Infectious agent detection by nucleic acid (DNA or RNA); Human Papillomavirus (HPV), high-risk types
87625	Infectious agent detection by nucleic acid (DNA or RNA); Human Papillomavirus (HPV), types 16 and 18 only, includes type 45, if performed
88342	Immunohistochemistry or immunocytochemistry, per specimen; initial single antibody stain procedure
88341	Immunohistochemistry or immunocytochemistry, per specimen; each additional single antibody stain procedure
0296U	Oncology (oral and/or oropharyngeal cancer), gene expression profiling by RNA sequencing at least 20 molecular features, saliva, algorithm reported as positive or negative for signature associated with malignancy (Proprietary test: mRNA CancerDetect™; Viome Life Sciences, Inc.)
0429U	Human papillomavirus (HPV), oropharyngeal swab, 14 high-risk types
81599	Unlisted multianalyte assay with algorithmic analysis

Codes associated with non-covered tests (listed for billing reference)CPTNot Covered

0296U	Proprietary test: mRNA CancerDetect™ (listed in policy as an example of gene expression profiling — policy states panels such as mRNA CancerDetect™ DO NOT MEET COVERAGE CRITERIA)
81599	Unlisted multianalyte assay with algorithmic analysis (may be used for proprietary saliva/genetic panel tests that are not covered)

Provider Actions

Documentation Required

Confirm oropharyngeal squamous cell carcinoma diagnosis

Providers must document that the individual has oropharyngeal squamous cell carcinoma when ordering testing to establish HPV tumor status (p16 IHC or HPV E6/E7 mRNA testing).

88342
88341
87624
0429U

Prior Authorization

Coverage dependent on member benefits and regulations

Application of coverage criteria is dependent upon an individual's benefit coverage at the time of the request; federal and state (Medicare/Medicaid) regulations may supersede this policy and must be followed.

Billing Rule

Procedure code use for proprietary/nonstandard tests

Use unlisted or appropriate CPT/HCPCS/PLA procedure codes for proprietary multianalyte or gene expression saliva tests; examples of such codes include unlisted multianalyte assay with algorithmic analysis and specific PLA codes. Proprietary saliva/gene-expression tests (for example, mRNA CancerDetect™ and OraRisk®) are identified in this policy as not meeting coverage criteria and may be denied.

81599
0296U

Background & Evidence

Epidemiology: Oral cavity and oropharyngeal cancers are common; the American Cancer Society estimated approximately 58,450 diagnoses and 12,230 deaths in 2024 for oral cavity and oropharyngeal cancers. Oral squamous cell carcinoma (OSCC) is the predominant histology.

Diagnostic considerations: Early detection often depends on conventional oral examination (COE) and scalpel biopsy with histology; many cases arise from potentially malignant disorders. Adjunctive tests (vital staining, brush cytology, chemiluminescence, autofluorescence, salivary biomarkers) have variable sensitivity and specificity across studies and are not recommended as replacements for COE followed by biopsy.

HPV and tumor testing: Human papillomavirus (HPV) is a major contributor to oropharyngeal cancers. Major professional organizations endorse using p16 immunohistochemistry (IHC) as a widely available surrogate marker with very good agreement with HPV E6/E7 mRNA to establish tumor HPV status for oropharyngeal cancers; alternate validated HPV nucleic acid assays may be used per guidance and confirmation practices.

Source	Summary
NCCN/ASCO/CAP guidance	Support p16 IHC as surrogate for HPV E6/E7 mRNA for oropharyngeal cancer
Systematic reviews/meta-analyses	Variable sensitivity/specificity for adjunctive screening tests; overall insufficient evidence to support salivary/genotyping/gene expression panels for screening

Oral cancer: Cancer 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.

HPV testing for tumor status: Testing to establish HPV tumor status using high-risk HPV E6/E7 mRNA expression testing or p16 immunohistochemistry (IHC) as a surrogate.