Multitarget Polymerase Chain Reaction Testing for Diagnosis of Bacterial Vaginosis

POLICY NUMBER

A.2.04.127

DESCRIPTION

Bacterial vaginosis (BV) is a common medical condition resulting from an imbalance in the normal vaginal flora. Although the identification of Gardnerella vaginalis has traditionally been associated with BV, there is no single etiologic agent. Most cases are asymptomatic, and most symptomatic cases can be diagnosed using clinical and microscopic evaluation. Multitarget polymerase chain reaction (PCR) testing is proposed as an alternative to currently available laboratory tests to diagnose BV. This test may improve outcomes if it is a more accurate and reliable method to diagnose BV.

Bacterial Vaginosis

BV is a condition caused by an imbalance in the normal bacteria vaginal flora. It is common, especially in women of reproductive age. While there is no single known etiologic agent, there is a shift in vaginal flora that involves depletion of hydrogen peroxide-producing Lactobacillus species with a rise in vaginal pH and overgrowth of other bacteria, including Gardnerella vaginalis, Mycoplasma hominis, Peptostreptococcus, Mobiluncus species, and other anaerobic gram-negative rods.

Vaginal culture is not an appropriate diagnostic method to identify BV because BV is not caused by the presence of a particular bacterial species.

Various commercial tests provide rapid and accurate pH evaluation and amine detection. For example, automated devices that measure the volatile gases produced from vaginal samples and a colorimetric pH test are commercially available.

Nucleic acid probes of DNA fragments are available to detect and quantify specific bacteria in vaginal fluid samples. Polymerase chain reaction (PCR) methods extract and amplify the DNA fragments using either universal or specific primers. The result can be qualitative (to assess whether a specific microorganism is present) or quantitative (to assess how many microorganisms are present). The technology can be used to measure multiple organisms (eg, those known to be associated with BV) at the same time and is commercially available as multitarget PCR testing.

The Identification of Microorganisms Using Nucleic Acid Probes medical policy addresses the use of direct or amplified nucleic acid probes with or without quantification to detect microorganisms of clinical significance, including single microorganisms associated with BV.

Multitarget PCR Tests

Five quantitative multiplex PCR assays are available: BD Max (Becton Dickinson), Aptima BV (Hologic), NuSwab VG (LabCorp), OneSwab BV Panel PCR with Lactobacillus Profiling by qPCR (Medical Diagnostic Laboratories), and SureSwab BV (Quest Diagnostics).

The SureSwab Total test involves obtaining vaginal swab specimens, extracting total DNA, and quantitating the four types of bacteria using PCR. Results are reported as log cells per milliliter for each organism and concentrations of all Lactobacilli species are reported together then classified into one of the following three categories: not supportive, equivocal, and supportive.

A classification of not supportive of BV diagnosis is based on:

• The presence of Lactobacillus species, G. vaginalis levels <6.0 log cells/mL, and absence of Atopobium vaginae and Megasphaera species; or

• The absence of Lactobacillus species, G. vaginalis levels <6.0 log cells/mL, and absence of A. vaginae and Megasphaera species; or

• The absence of all targeted organisms.

A classification of equivocal is based on:

• The presence of Lactobacillus species, plus G. vaginalis at least 6.0 log cells/mL, and/or presence of A. vaginae and/or Megasphaera species.

A classification of supportive of BV diagnosis is based on:

• The absence of Lactobacillus species, and presence of G. vaginalis levels of at least 6.0 log cells/mL, and presence of A. vaginae and/or Megasphaera species.

The BD Max (Becton, Dickinson), tests for markers of BV and vaginitis. The test uses a similar process to that described for SureSwab. Vaginal swab specimens are collected, DNA is extracted, and real-time PCR is used to quantitate targeted organisms. Results of BV marker tests are not reported for individual organisms. Instead, qualitative BV results are reported as positive or negative for BV based on the relative quantity of the various organisms.

The Aptima BV Assay was cleared by the U.S. Food and Drug Administration with the BD Max as the predicate device. The Aptima assay is a nucleic acid amplification test (NAAT) for detection and quantitation of ribosomal RNA.

Medical Diagnostics Laboratory offers a Bacterial Vaginosis Panel. Markers are assessed using real-time PCR and Lactobacillus is profiled using quantitative PCR. GenPath Diagnostics also offers a bacterial vaginosis test.

The NuSwab Select BV test (Laboratory Corporation of America) uses semiquantitative PCR analysis of three predictive marker organisms of vaginal dysbiosis to generate a total score that is associated with the presence or absence of BV. In this test system, samples with a total score of 0 to 1 are considered negative for BV, samples with a score of 3 to 6 are positive for BV, and samples with a score of 2 are indeterminate for BV.

Two assays are FDA cleared (BD Max and Aptima BV), and 3 (NuSwab VG, OneSwab BV Panel PCR with Lactobacillus Profiling by qPCR, and SureSwab BV) are laboratory-developed tests.

Several of the manufacturers of the BV tests also have extensions that include other causes of vaginitis such as Trichomonas vaginalis and Candidiasis species. For example, the BD Vaginal Panel was cleared in March 2023 with the BD Max as the predicate device. It is intended to aid in the diagnosis of vaginal infections in individuals with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis and trichomoniasis.

Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests (LDTs) must meet the general regulatory standards of the Clinical Laboratory Improvement Act (CLIA). Laboratories that offer LDTs must be licensed by the CLIA for high-complexity testing.

Related medical policies –

• Identification of Microorganisms Using Nucleic Acid Probes

POLICY

Multitarget polymerase chain reaction (PCR) testing for the diagnosis of bacterial vaginosis is considered investigational.

POLICY EXCEPTIONS

None

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting. 

POLICY HISTORY

04/09/2015: Approved by Medical Policy Advisory Committee.

08/04/2015: Code Reference section updated for ICD-10.

01/15/2016: Policy description updated regarding laboratory-developed tests. Policy statement unchanged.

06/07/2016: Policy number A.2.04.127 added.

08/16/2017: Policy description updated regarding tests. Policy statement unchanged. Policy Guidelines updated.

01/23/2019: Policy description updated regarding bacterial vaginosis and multitarget PCR tests. Policy statement unchanged. Policy guidelines updated to remove diagnostic criteria.

01/20/2020: Policy description updated regarding tests. Policy statement unchanged.

02/03/2021: Policy reviewed; no changes.

02/03/2022: Policy reviewed; no changes.

06/27/2022: Code Reference section updated to add new CPT code 0330U, effective 07/01/2022.

09/13/2022: Code Reference section updated to add new CPT codes 0352U and 0353U. Effective 10/01/2022.

04/01/2023: Policy description updated regarding proposed multitarget PCR tests. Policy statement unchanged. Code Reference section updated to add CPT codes 81513 and 81514.

09/25/2023: Code Reference section updated to add new CPT code 0402U, effective 10/01/2023.

01/09/2024: Policy description updated regarding panels. Policy statement unchanged.

06/27/2024: Code Reference section updated to make note of deleted CPT code 0353U. Effective 06/30/2024.

10/01/2024: Code Reference section updated to add new CPT code 0505U.

12/19/2024: Code Reference section updated to add new CPT code 81515 effective 01/01/2025.

02/06/2025: Policy reviewed; no changes.

07/18/2025: Code Reference section updated to add new CPT code 0557U, effective 07/01/2025. Removed deleted CPT code 0353U.

SOURCE(S)

Blue Cross and Blue Shield Association Policy # 2.04.127

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

Investigational Codes

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