Blue Cross Blue Shield TN STI Testing Coverage

Coverage criteria for STI diagnostic testing

Syphilis testing (antibody)

Syphilis antibody testing MEETS COVERAGE CRITERIA when any of the following conditions are met

Syphilis antibody testing indications: a) Annual screening for any asymptomatic person in a high-risk category using a standard or reverse algorithm that includes initial and confirmatory tests (eg, treponemal Ig and nontreponemal test); b) Diagnosis of any person presenting with signs and/or symptoms of syphilis; c) Every three months for HIV-positive men or men who have sex with men (MSM); d) Pre-transplant treponemal and nontreponemal testing (once prior to transplant) for both donors and recipients of allogeneic hematopoietic stem cell transplantation (allo-HCT); e) When a nontreponemal test is used as a test-of-cure (TOC) for a positive syphilis infection.

High-risk groups defined in Note 2 (eg, MSM, sexually active HIV-positive persons, partners recently diagnosed with an STI, persons exchanging sex for money/drugs, incarcerated individuals, pregnancy with specific risk factors).

Syphilis not covered

Not covered for syphilis: Polymerase chain reaction (PCR) testing and nucleic acid amplification testing (NAAT) for Treponema pallidum (syphilis) DO NOT MEET COVERAGE CRITERIA.

PCR/NAAT for genital syphilis are not FDA-approved for routine diagnosis and require validated methods if used.

Chlamydia testing (NAAT)

NAAT for Chlamydia trachomatis MEETS COVERAGE CRITERIA in these scenarios

Chlamydia NAAT indications: a) Annual screening for any asymptomatic person in a high-risk category; b) Diagnosis of any person presenting with signs and/or symptoms of chlamydial infection; c) Diagnosis of suspected lymphogranuloma venereum (LGV); d) At least three months after initial chlamydial diagnosis as a test-of-cure (TOC).

For asymptomatic individuals not in high-risk groups, screening meets coverage only in specific situations (eg, newborn screening, sexual assault follow-up, sexually active individuals <18 annually).

Chlamydia serology not covered

Chlamydia serology: Serology testing for Chlamydia trachomatis or LGV DOES NOT MEET COVERAGE CRITERIA.

NAATs are the recommended diagnostic modality; serology cannot reliably distinguish past from current LGV infection.

Gonorrhea testing

NAAT for Neisseria gonorrhoeae MEETS COVERAGE CRITERIA in these scenarios

Gonorrhea NAAT indications: a) Annual screening for any asymptomatic person in a high-risk category; b) Diagnosis of any person presenting with signs and/or symptoms of gonorrhea; c) As a test-of-cure following treatment when indicated; d) Culture testing for antimicrobial susceptibility MEETS COVERAGE CRITERIA when an individual does not respond to initial treatment (culture reserved for susceptibility testing/ suspected treatment failure).

For asymptomatic non-high-risk individuals, screening meets coverage only for newborns, sexual assault follow-up, and sexually active individuals <18 annually.

Trichomonas vaginalis testing

Testing for Trichomonas vaginalis MEETS COVERAGE CRITERIA when the following apply

Trichomonas NAAT indications: a) Symptomatic individuals with signs of trichomoniasis; b) Asymptomatic individuals belonging to high-risk groups (eg, concurrent STI or history of STIs, individuals in high-prevalence settings such as STI clinics, individuals who exchange sex for payment).

Rapid enzyme immunoassay identification of Trichomonas DOES NOT MEET COVERAGE CRITERIA; NAAT or PCR-based testing preferred.

Mycoplasma genitalium testing

M. genitalium NAAT indications: NAAT testing for Mycoplasma genitalium MEETS COVERAGE CRITERIA for symptomatic individuals (eg, men with recurrent nongonococcal urethritis, women with recurrent cervicitis or suspected M. genitalium-associated PID). Screening asymptomatic individuals with NAAT DOES NOT MEET COVERAGE CRITERIA.

When available, resistance testing is recommended to guide therapy; culture is impractical.

Multitarget PCR panels

Multitarget PCR: When an individual meets any of the covered conditions for CT, NG, TV, or MG, multitarget PCR panels that target only Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium MEET COVERAGE CRITERIA.

Multiplex assays limited to these targets are acceptable when clinical indications are met.

Herpes simplex virus testing

HSV testing indications: a) NAAT for HSV-1 or HSV-2 meets coverage for individuals with active genital ulcers or mucocutaneous lesions; b) Type-specific serologic testing for HSV-2 (glycoprotein G2) meets coverage for recurrent or atypical genital symptoms or lesions when PCR/culture is negative, for clinical diagnosis without laboratory confirmation, or when a partner has genital herpes; c) Immunoassay non-type-specific serologic testing DOES NOT MEET COVERAGE CRITERIA; d) Screening asymptomatic individuals for HSV-1/HSV-2 DOES NOT MEET COVERAGE CRITERIA.

HSV DNA detection (NAAT) is the preferred diagnostic method for lesions; routine serologic screening is discouraged due to false positives and potential psychosocial harms.

Human papillomavirus testing

HPV testing indications and limits: a) High-risk HPV (HR-HPV) testing meets coverage for diagnosis or assessment of cancer or cancer therapy (eg, p16 IHC, NAAT for HR-HPV) and for cervical cancer screening in accordance with guideline age thresholds; b) HPV testing DOES NOT MEET COVERAGE CRITERIA when used as part of general STI panels for asymptomatic individuals, to diagnose anogenital warts, to screen for low-risk HPV types, or as general population NAAT to determine HPV status (no routine testing for men or women <30).

HPV screening for cervical cancer recommended for women aged ≥30 per guidelines; BD Onclarity indications summarized separately.

PrEP baseline and follow-up testing

Preexposure prophylaxis (PrEP) baseline and monitoring: Prior to PrEP initiation, coverage includes baseline serum creatinine/estimated creatinine clearance, HIV antigen/antibody screening (baseline negative), hepatitis B/C screening, and pregnancy testing. While on PrEP, coverage includes HIV antibody testing every 3 months, serum creatinine at 3 months then up to every 6 months thereafter, NAAT screening for gonorrhea and chlamydia by anatomic site at recommended intervals (eg, every 3 months for MSM and individuals with child-bearing potential; 9 months after initiation then every 6 months for sexually active individuals), syphilis blood test every 3 months for MSM and individuals with child-bearing potential (similar schedule for others), and pregnancy testing every 3 months.

Follow CDC PrEP monitoring schedule; document baseline and follow-up testing per guidance.

Tests lacking coverage

Not covered tests: Nucleic acid testing to determine antimicrobial susceptibility in Neisseria gonorrhoeae or macrolide resistance in Mycoplasma genitalium DOES NOT MEET COVERAGE CRITERIA. Nucleic acid quantification for Chlamydia trachomatis, Neisseria gonorrhoeae, HSV-1, HSV-2, Human papillomavirus, and Treponema pallidum DOES NOT MEET COVERAGE CRITERIA.

These tests lack sufficient evidence of clinical benefit for routine coverage.

Diagnostic testing coverage and indications

Covered diagnostic testing and indications as described in document excerpts:

Chlamydia and Gonorrhea testing: NAAT is the preferred diagnostic method for chlamydia and gonorrhea due to superior sensitivity and specificity; test genital, rectal, and pharyngeal sites as clinically indicated (first-catch urine or site-specific swabs).

Culture reserved for medico-legal cases and antimicrobial susceptibility (gonorrhea).

Mycoplasma genitalium: Consider NAAT testing for M. genitalium in symptomatic patients with urethritis, cervicitis, or PID; prevalence higher in care-seeking populations. Resistance testing recommended when available to guide therapy.

Culture impractical; NAAT cleared for urine and genital swabs.

Syphilis testing: Use two-tier serologic testing (treponemal and nontreponemal tests) for syphilis diagnosis; direct detection (darkfield, PCR) may be used for lesions but PCR/NAAT are not routinely available commercially for genital syphilis.

If TT used as primary screen, reflex quantitative NTT is required when positive or discrepant.

HPV assay intended uses and age-based indications

Assay uses and clinical actions described in the text:

BD Onclarity HPV intended uses: BD Onclarity HPV Assay is indicated in women >=21 with ASC-US to determine need for colposcopy and to detect HR HPV genotypes 16, 18, and 45; in women >=30 it can be used adjunctively with cytology for screening and to detect genotypes 16/18/45; in women >=25 it can be used as a first-line primary cervical cancer screening test. Positive 16/18 results should prompt referral to colposcopy per manufacturer labeling.age thresholds as stated

Manufacturer indications summarized from FDA labeling.

CT/NG NAAT specimen-specific performance

CT/NG NAAT performance and specimen considerations:

Cepheid Xpert CT/NG specimen and performance notes: FDA-approved NAATs such as Cepheid Xpert CT/NG are validated for urogenital and selected extragenital (pharyngeal, rectal) specimens; overall sensitivity and specificity are high (mid–high 90s%), though rectal swab sensitivity can be lower (eg, ~86% for CT and ~91.2% for NG) while specificity remains ~99%.specimen-dependent sensitivity values

Near-patient NAATs provide faster turnaround and can facilitate same-day treatment; specimen collection method affects performance.

Syphilis testing performance and utility

Syphilis testing considerations:

Serology vs molecular for T. pallidum: EIA-based serologic treponemal tests demonstrate high sensitivity and specificity in some studies; molecular tests (PCR/TMA) can detect mucosal infections but have lower sensitivity in some cohorts (eg, ~50% sensitivity in one MSM study) and may add little additional clinical value over serology in many settings. A combinatory approach (mucosal molecular testing plus serology) may improve detection in selected populations.study-specific sensitivities/specificities

Reflex quantitative testing and two-test serologic algorithms remain standard per guidance.

HSV serologic testing considerations

HSV serologic screening considerations:

HSV-2 serology utility and harms: Pooled estimates for commonly used HSV-2 serologic tests show high sensitivity (~99%) but lower specificity (~81%) at manufacturer's cutpoints; in populations with moderate prevalence this yields a substantial number of false positives and psychosocial harms. Viral detection by PCR (lesions) or culture (less sensitive) remains the preferred diagnostic approach for acute disease; serology is useful in selected scenarios (recurrent/atypical symptoms, partner evaluation).manufacturer cutpoint performance

USPSTF warns against routine serologic screening of asymptomatic persons due to harms from false positives.

Guideline-based coverage criteria

Coverage aligned with guideline-based indications and specimen/testing method recommendations:

Chlamydia and Gonorrhea Screening: Screen sexually active females <=24 years and women >=25 years who are at increased risk; use NAATs on appropriate specimen types (first-catch urine or site-specific swabs); consider screening men in high-prevalence settings.age & risk-based

Follow CDC and USPSTF recommendations; test extragenital sites based on exposure.

Gonorrhea Diagnostic & Susceptibility: Use NAATs for diagnosis from urogenital and extragenital sites; maintain culture capacity for antimicrobial susceptibility testing and suspected treatment failure; perform NAAT follow-up as guideline-directed for specific sites.clinical site-specific

Culture still required for susceptibility and certain medico-legal contexts.

Syphilis Testing Algorithm:

Syphilis: Screening and confirmatory testing

Syphilis testing algorithms and follow-up

Algorithm choice: If using a treponemal test (TT) as the primary screen, automated EIA/ELISA/CLIA methods are suitable for high-throughput screening but may yield low positive predictive value in low-prevalence populations; NTT-based algorithms (RPR/VDRL) are preferably quantitative to detect prozone phenomenon.

Choose algorithm based on population prevalence and lab capabilities.

Reflex testing after positive TT: When TT alone is positive, perform a reflex quantitative non-treponemal test (NTT) on the same serum reaching at least 1:8 to 1:16 dilution; if TT positive and NTT negative with no suspicion of early syphilis, repeat both tests after 1 month.repeat after 1 month for discordant tests

Reflex confirmatory TT of different type may be used for counseling but has limited impact on treatment decisions.

If NTT used as primary screen: A positive NTT must be followed by a reflex treponemal test on the same serum; if the initial NTT was not quantitative, repeat it quantitatively.

Chlamydia and Gonorrhea: Testing and follow-up

Chlamydia and Gonorrhea testing

Preferred test: NAATs are the most sensitive and specific tests for chlamydia and gonorrhea and may be performed on urine, urethral, vaginal, cervical swabs and, where validated, on pharyngeal and rectal specimens.

Use culture when antimicrobial susceptibility testing is needed or for medico-legal cases; test extragenital sites per exposure.

Test-of-cure and follow-up: Test-of-cure considerations: culture 3-7 days or NAAT 2-3 weeks post-treatment when second-line therapy used, resistance suspected, compliance uncertain, pharyngeal/rectal infection, disseminated infection, persistent symptoms, pregnancy, or adolescents; rescreen positive patients at approximately 3 months.3-7 days culture; 2-3 weeks NAAT

Follow guideline-specified intervals for retesting and test-of-cure.

Herpes Simplex Virus (HSV): Diagnosis

HSV testing

Preferred diagnostic method: HSV DNA detection by NAAT is the preferred/gold-standard diagnostic method for active lesions; viral culture is less sensitive and may miss PCR-positive samples. Routine serologic testing is not recommended for asymptomatic patients but may be useful in selected groups (pregnant women, partners, recurrent/atypical disease).

Type-specific serology can aid in counseling and management in specific contexts.

Specimen recommendations: For oral or anogenital lesions collect lesion swabs for NAAT; for suspected proctitis obtain rectal mucosal swabs; consider virus typing for newly diagnosed cases to differentiate HSV-1 from HSV-2 when clinically useful.

NAAT preferred for sensitivity and rapid turnaround; culture may be used when NAAT unavailable.

HPV: Clinical role and testing

HPV and other guidance

HPV in cancers and screening utility: HPV testing (DNA/RNA or p16 IHC) is valuable for prognosis and management in certain cancers and for cervical cancer screening per guidelines; testing for HPV types is not routinely useful for diagnosis of anogenital warts and is not recommended for asymptomatic men or women under 30.

Refer to guideline-specific age-based screening intervals and indications (eg, screening women 30-65).

Organism-specific guideline-aligned coverage criteria

Coverage is informed by cited guideline recommendations and varies by organism and patient population.

HPV screening for cervical cancer: HPV testing to screen for cervical cancer is recommended for women aged 30 years and older and is not recommended for men, adolescents, or women under age 30.age >= 30

Follow guideline frequencies for co-testing vs HPV-alone screening.

Chlamydia and Gonorrhea screening: NAAT testing is recommended for sexually active women under 25 and for older women/men in high-risk groups; routine testing is not recommended for asymptomatic men and older women unless high-risk or symptomatic.age <=25 or high-risk

Screening intervals and retesting per CDC/USPSTF guidance.

Syphilis testing: Use both a treponemal and a non-treponemal test for presumptive diagnosis; perform darkfield exam or PCR when lesions are present if available; screen high-risk asymptomatic patients per CDC/USPSTF guidance.

The policy identifies several molecular and serologic tests that DO NOT MEET COVERAGE CRITERIA in general use: specifically, NAAT/PCR testing for Treponema pallidum (syphilis) is listed among tests not meeting coverage. The document also states that serology testing for Chlamydia trachomatis/LGV is not covered, and that point-of-care rapid enzyme immunoassays for identification of Trichomonas vaginalis lack sufficient evidence to meet coverage. Additionally, the policy excludes routine use of nucleic acid-based quantification or other nucleic acid assays for listed organisms when used outside supported clinical indications.

The policy notes that NAAT/PCR is not FDA-approved for routine genital syphilis diagnosis and that PCR testing for T. pallidum requires laboratory methods that are strictly validated with appropriate quality controls. Because no internationally approved PCR assay for T. pallidum exists, molecular testing for genital syphilis should not be used as a routine diagnostic substitute for guideline-recommended serologic algorithms unless performed as a validated laboratory-developed test under appropriate CLIA high-complexity processes.

Comparative evidence summarized in the policy shows that molecular detection of T. pallidum has lower sensitivity in some series than serologic testing (examples include reported PCR sensitivities around ~68% (or lower in some studies)) while serologic assays demonstrate higher sensitivity. The document concludes that T. pallidum PCR may add little clinical value over standard serology in many settings, because most PCR-positive patients also have positive serology and serology remains the accepted diagnostic standard.

HPV testing for cervical cancer screening is age- and indication-specific. The policy reiterates guideline recommendations that HPV testing (for screening) is appropriate for women aged 30 and older but emphasizes that routine HPV testing is NOT recommended for men, adolescents, or women under age 30. The document also states that HPV testing should not be used to diagnose anogenital warts or as part of general asymptomatic STI panels where results do not change management.

Consistent with USPSTF and guideline conclusions, the policy states that routine serologic testing for HSV-2 in asymptomatic patients does NOT meet coverage criteria. It also notes that routine syphilis screening is not recommended for asymptomatic, low-risk heterosexual adolescents and that screening frequency and populations should follow established high-risk criteria in guidelines.

The policy specifies that HPV testing is not indicated for asymptomatic men, adolescents, or women under 30 and that testing for HPV should not be used to diagnose anogenital warts because such results do not alter clinical management. HPV assays are covered when used for cancer diagnosis or therapy assessment (for example, p16 IHC or NAAT for high-risk HPV) in appropriate clinical contexts.

Procedure and screening codes listed in this policy are provided only as a general reference and may not be all-inclusive. Providers should use the exact CPT/HCPCS code(s) appropriate to the service and follow standard billing guidance when submitting claims.

The reference listings in this section do not state explicit coverage exclusions beyond the organism- and method-specific criteria given elsewhere; they serve primarily as bibliographic support for the policy statements rather than as standalone exclusions.

The policy designates certain uses as not meeting coverage: screening asymptomatic individuals for HSV-1/2 and the use of HPV testing as part of general STI screening panels or to determine HPV status in asymptomatic persons are specifically identified as excluded from coverage. These items reflect guideline-based recommendations against routine serologic HSV screening and against indiscriminate HPV NAAT testing in asymptomatic populations.

Because PCR testing for Treponema pallidum currently lacks an internationally approved standard and because published guidance stresses strict validation and quality control, the policy states that routine PCR testing for syphilis is not standard or approved and is not recommended without validated methodology.

The policy summarizes evidence from systematic reviews showing that antigen-detection point-of-care tests (POCTs) for Chlamydia trachomatis have inadequate sensitivity for screening (pooled sensitivities reported across sample types in the range of approximately 37–63%), whereas near-patient NAATs demonstrate substantially higher sensitivity and specificity and are favored when rapid molecular testing is available.

Reflecting USPSTF and international guideline guidance, the policy advises that routine serologic screening for genital herpes in asymptomatic adolescents and adults (including pregnant persons) is not recommended due to a high false-positive rate and potential psychosocial harms.

The USPSTF recommendation against routine testing of asymptomatic patients for HSV-2 is cited; the policy therefore considers routine serologic screening of asymptomatic individuals for HSV-2 to be not recommended and not meeting coverage criteria in the absence of specific clinical indications.

This section of the policy provides reference citations and background literature to support the coverage statements; it does not itself specify additional 'not medically necessary' determinations beyond those described in the coverage and exclusion sections.

What providers must do

Prior Authorization

Verify benefits / Prior authorization

Verify member benefits and any prior authorization requirements before ordering tests. Application of coverage criteria depends on the individual’s benefit coverage at the time of request; Medicare/Medicaid (LCD/NCD or state Medicaid) requirements take precedence where applicable.

Verify member-specific benefits and prior authorization rules prior to testing requests.
If government policy (e.g., LCD/NCD or state Medicaid) conflicts with this policy, follow the government policy.

Billing Rule

Proprietary and multiplex test codes

Some proprietary and multiplex assays are listed in the policy; confirm payer acceptance and any special billing or documentation requirements before ordering.

Proprietary/multiplex tests listed include assays such as Abbott Alinity™ m STI Assay, BioPlex 2200 RPR Assay, and several lab-specific LDTs (see proprietary code listings).
Providers should confirm if a specific proprietary test requires prior authorization or other payer-specific steps.

Billing Rule

Code-specific billing and reimbursement review

Bill using the exact CPT/HCPCS/other procedure codes that correspond to the performed test. Procedure codes in the policy are for reference only and may not be all-inclusive.

Use the appropriate CPT/HCPCS code associated with the performed assay; procedure codes in this policy are reference tools only.
Claims may be subject to coding-linked reimbursement review when specific infectious agent detection or antibody screening codes are billed.

Denial Risk

Denial triggers / Tests that do not meet coverage

Tests explicitly listed as not meeting coverage criteria are denial triggers; avoid routine use of these tests unless covered by member benefits or required by government policy.

NAAT or PCR for syphilis, serology for chlamydia/LGV, and nucleic acid testing to determine antimicrobial susceptibility in N. gonorrhoeae or macrolide resistance in M. genitalium are listed as NOT meeting coverage criteria.
Quantitative nucleic acid testing to quantify organisms (eg, C. trachomatis, N. gonorrhoeae, HSV-1/2, HPV, T. pallidum) is listed as not meeting coverage criteria.

Documentation Required

HIV testing prior to PrEP

Follow CDC guidance for HIV testing before initiating or re-initiating PrEP: confirm a negative HIV antigen/antibody result within 1 week prior to PrEP start (or use an FDA-approved rapid blood test). Do not use oral rapid tests for PrEP screening.

Obtain HIV antigen/antibody testing (laboratory or rapid fingerstick blood test) with a negative result within 7 days before starting or restarting PrEP.
Oral rapid antibody tests should not be used for PrEP screening due to lower sensitivity.

Note

No explicit prior authorization / step therapy stated

No additional explicit provider-facing prior authorization or step-therapy requirements are stated in this section beyond verifying member benefits; follow payer-specific policies where applicable.

The policy does not specify uniform prior authorization rules for the listed proprietary assays; verify with the payer.
No step therapy requirements are specified in this section.

Documentation Required

Syphilis dual-test requirement

When performing serologic testing for syphilis, use a two-test algorithm (treponemal and nontreponemal); relying on only one serologic test type is insufficient for diagnosis and may lead to false results.

Use both a treponemal test (TT) and a nontreponemal test (NTT) for diagnosis or screening per recommended indications.
For asymptomatic low-risk screening, syphilis serology meets coverage only in specified situations (eg, newborns, sexual assault follow-up, sexually active <18).

Documentation Required

Quantitative non-treponemal test (NTT) requirement

If both a treponemal test (TT) and a nontreponemal test (NTT) are used as primary screening, ensure the NTT is performed quantitatively (or repeat quantitatively if not initial).

A reflex quantitative NTT (eg, reach at least 1:8 to 1:16 dilution) should be performed on the same serum when indicated.
If an NTT was used without quantitative measurement, repeat the NTT quantitatively when necessary.

Documentation Required

PrEP baseline and follow-up testing documentation

Document PrEP baseline and follow-up testing as recommended: baseline HIV antigen/antibody negative within 1 week prior to initiation, baseline renal function, HBV screening, and follow recommended intervals for repeat testing (eg, HIV at 3 months, renal at 3–6 months, STI screening per risk).

Document a negative HIV antigen/antibody test within 7 days prior to starting PrEP (or use a rapid fingerstick blood test).
At 3 months after PrEP initiation: test for HIV, measure serum creatinine/CrCl, provide adherence counseling; at recommended intervals thereafter continue HIV and renal monitoring and STI screening per CDC guidance.

Documentation Required

Syphilis reflex testing documentation

When a treponemal test (TT) alone is used and is positive, perform a reflex quantitative non-treponemal test (NTT) on the same serum; when an NTT alone is positive, perform a reflex TT. Repeat testing strategies are described for discrepant results.

Positive TT alone → reflex quantitative NTT on same serum (and repeat both tests after 1 month if TT positive, NTT negative, and no suspicion of early syphilis).
Positive NTT alone → reflex TT on same serum; if initial NTT was non-quantitative, repeat NTT quantitatively.

Billing Rule

Procedure code documentation and coding review

Procedure and billing codes included in this policy are provided for reference to support documentation and claims submission; they may not be exhaustive. Confirm appropriate codes for the specific test performed.

Examples of listed codes include proprietary and HCPCS/CPT codes (eg, 0096U, 0210U, 0402U, 0455U, 0463U, 0483U, 0484U, 0500T, G0432–G0435, G0472, G0475, G0499, S3645).
Providers must include applicable procedure code(s) on claims and be prepared for coding-linked reimbursement review.

Note

No other provider-facing authorization or documentation specified

No additional provider-facing authorization or documentation requirements beyond those called out here are specified in this section; consult payer or government policies for member-specific rules.

Providers should maintain documentation that supports medical necessity for testing and billing.
If unsure about coverage or documentation expectations, contact the payer prior to testing.

Step Therapy

Step therapy / Ordering pathway

Ordering pathway considerations: no step-therapy sequencing is specified. Rapid NAAT/POC tests may improve management by reducing under- or overtreatment, but ordering should follow clinical indications and payer rules.

There are no step therapy requirements in this policy segment.
Consider use of rapid NAAT/POC tests when clinically appropriate and allowed by payer coverage to optimize treatment decisions.

Key definitions and abbreviations

inv-79: High-risk

Definition (examples)High-risk populations include men who have sex with men (MSM) and sexually active HIV-positive persons

Additional high-risk groupsIndividuals with recent STI exposure, those exchanging sex for money or drugs, and persons in correctional facilities

Pregnancy & youthPregnant persons with additional risk factors and sexually active youth under 18 with risk factors are considered high-risk

inv-80: NAAT

DefinitionNucleic acid amplification testing (NAAT): PCR-based methods that detect pathogen DNA/RNA and are the preferred, more sensitive molecular tests for many STIs

Typical usesGold-standard diagnostic method for Chlamydia trachomatis and Neisseria gonorrhoeae; used for extragenital specimens where validated

Point-of-care variantsNear-patient NAAT platforms exist (eg, Cepheid Xpert) that provide rapid results and can be used on validated specimen types

inv-81: BD Onclarity HPV Assay

Assay descriptionBD Onclarity HPV Assay: an FDA-approved qualitative PCR-based NAAT for cervical swabs that identifies HPV genotypes 16, 18, and 45 and detects other high-risk HPV types

Indicated usesIndicated for women 21+ with ASC-US to guide colposcopy referral; adjunctive screening with cytology in women 30+; can be used as first-line screening in women 25+ per manufacturer

Reporting implicationsPositive results for types 16/18 should prompt consideration of colposcopy per manufacturer guidance

inv-82: Near-patient NAAT / rapid NAAT

DefinitionNear-patient (rapid) NAAT: nucleic acid amplification tests performed near the point of care (eg, Xpert CT/NG on GeneXpert) that return results in approximately 90–115 minutes

Specimen scopeFDA-approved for multiple specimen types including urine, clinician- or patient-collected vaginal swabs, endocervical swabs, and pharyngeal/rectal swabs as validated

Clinical valueFaster turnaround can improve emergency department and same-day treatment decisions compared with central lab testing

inv-83: Serologic HSV testing (type-specific)

Test typeType-specific serologic HSV testing detects HSV-2 antibodies (eg, glycoprotein G-based assays) via blood-based assays

PerformancePooled sensitivity ~99% and specificity ~81% at manufacturer's cutpoint; positive predictive value is limited in low-prevalence populations leading to many false positives

Clinical useRecommended for recurrent/atypical genital symptoms with negative PCR/culture, clinical diagnosis without lab confirmation, or when partner has genital herpes; not for routine asymptomatic screening

inv-84: TT

DefinitionTT (Treponemal tests): e.g., TPHA, TPPA, EIA/ELISA/CLIA used for syphilis screening or confirmation

Role in algorithmTTs are used in primary screening algorithms and are more sensitive for very early syphilis compared to NTTs; positive TT often triggers reflex quantitative NTT

ExamplesAutomated EIA/ELISA/CLIA platforms commonly used for high-throughput screening in asymptomatic populations

inv-85: NTT

DefinitionNTT (Non-treponemal tests): e.g., RPR, VDRL used to detect active syphilis and for quantitative monitoring

Quantitative requirementWhen used as part of primary screening or following a positive TT, NTT must be performed quantitatively to detect activity and prozone phenomenon

ExamplesRPR and VDRL are preferred NTTs; quantitative titers guide treatment response monitoring

inv-86: TT

DefinitionTreponemal tests (TT): TPHA, MHA-TP, TPPA or EIA/ELISA/CLIA used for syphilis screening and confirmation

Screening implicationTT-based algorithms are suitable for automated high-throughput screening but may yield false positives in low-prevalence populations

Confirmation pathwayPositive TT may prompt reflex quantitative NTT and, where specificity is suboptimal, confirmatory TPHA/TPPA

inv-87: NTT

DefinitionNTT (non-treponemal tests) such as RPR or VDRL detect active syphilis and should be performed quantitatively when used in screening or follow-up

Reflex useA positive NTT must be followed by reflex TT on the same serum; if initial NTT was not quantitative, repeat quantitatively

Clinical monitoringQuantitative NTT titers are used to monitor treatment response and detect prozone phenomenon

inv-88: NAAT

DefinitionNAAT: nucleic acid amplification tests (DNA/RNA) recommended for detection of Chlamydia trachomatis and Neisseria gonorrhoeae and for various extra-genital specimens

Specimen typesCan be performed on urine, urethral, vaginal, cervical, pharyngeal, and rectal specimens as clinically indicated and validated by lab/manufacturer

AdvantagesHigher sensitivity and specificity compared with antigen-based POCTs or culture for many specimen types

inv-89: NAAT

DefinitionNAAT (nucleic acid amplification testing) — preferred, more sensitive molecular testing for many STIs such as chlamydia and gonorrhea

RecommendationUse NAAT for screening and diagnosis where available; consider extragenital NAAT for exposures at those sites

LimitationsSome NAATs have variable performance by specimen type; consult manufacturer and lab validation data

inv-90: LDT

DefinitionLDT (Laboratory-developed test): assays developed and validated by individual laboratories and regulated under CLIA as high-complexity tests; not FDA-approved

Regulatory noteLDTs must be validated and performed in-house under CLIA high-complexity requirements; documentation of validation may be required when billed

Clinical implicationLDTs can be used clinically but require laboratory validation and appropriate reporting of performance characteristics

inv-91: RPR/VDRL and treponemal tests

Combined approachNon-treponemal tests (eg, RPR, VDRL) and treponemal antibody tests are used in combination per guidelines for syphilis diagnosis

Role differentiationNTTs detect active infection and are quantitative; TTs detect treponemal-specific antibodies and may remain positive for life

Algorithm requirementIf TT used as primary screen and positive, reflex quantitative NTT should be performed; if NTT used first, follow with TT

inv-93: Mycoplasma genitalium macrolide sensitivity (23S rRNA point mutation)

Target mutationM. genitalium macrolide sensitivity testing detects point mutations in 23S rRNA associated with macrolide resistance

MethodTypically performed by molecular assays (proprietary codes referenced) to inform antimicrobial therapy selection

Coding exampleProprietary code 0484U is associated with Mycoplasma genitalium macrolide sensitivity testing

inv-94: HPV extended genotyping

DefinitionHPV extended genotyping: nucleic acid-based detection reporting five or more individually reported high-risk HPV types (eg, CPT/Proprietary code 0500T)

Use caseGenotyping may be used in diagnostic or cancer-related contexts where specific high-risk types inform management

Coding examplesProprietary code 0500T and related genotyping codes identify multiple HR-HPV types separately reported

inv-95: Genital herpes, syphilis, gonorrhoea, HPV

Conditions coveredClinical conditions referenced across the policy include genital herpes, syphilis, gonorrhoea, and HPV among others

ScopePolicy limited to testing for C. trachomatis, N. gonorrhoeae, T. pallidum, T. vaginalis, HSV, HPV, and M. genitalium

Clinical relevanceGuidance aligns testing methods (eg, NAAT, serology, culture) with diagnostic and screening indications for these conditions

NAAT	Nucleic acid amplification testing (general term; multiple CPT codes exist)
PCR	Polymerase chain reaction (general term; multiple CPT codes exist)
RPR/VDRL	Nontreponemal serologic tests for syphilis (rapid plasma reagin, VDRL)
TPPA/TP-PA/MHA-TP	Treponemal tests (particle agglutination, microhemagglutination)

82565	Creatinine; blood.
82575	Creatinine; clearance.
84702	Gonadotropin, chorionic (hCG); quantitative.
84703	Gonadotropin, chorionic (hCG); qualitative.
86592	Syphilis test, non-treponemal antibody; qualitative (eg, VDRL, RPR, ART).
86593	Syphilis test, non-treponemal antibody; quantitative.
86631	Antibody; Chlamydia.
86632	Antibody; Chlamydia, IGM.
86694	Antibody; herpes simplex, non-specific type test.
86695	Antibody; herpes simplex, type 1.

0484U	Infectious disease (Mycoplasma genitalium), macrolide sensitivity (23S rRNA point)
0500T	Infectious agent detection by nucleic acid (DNA or RNA), Human Papillomavirus (HPV) for five or more separately reported high-risk HPV types (ie, genotyping)
G0432	Infectious agent antibody detection by enzyme-linked immunosorbent assay (ELISA) technique, HIV-1 and/or HIV-2, screening
G0433	Infectious agent antibody detection by enzyme-linked immunosorbent assay (ELISA) technique, HIV-1 and/or HIV-2, screening
G0435	Infectious agent antibody detection by rapid antibody test, HIV-1 and/or HIV-2, screening
G0472	Hepatitis C antibody screening, for individual at high risk and other covered indication(s)
G0475	HIV antigen/antibody, combination assay, screening
G0499	Hepatitis B screening in non-pregnant, high risk individual includes hepatitis B surface antigen (HBSAG) followed by a neutralizing confirmatory test for initially reactive results, and antibodies to HBSAG (anti-HBs) and Hepatitis B core antigen (anti-HBc)
S3645	HIV-1 antibody testing of oral mucosal transudate.

OpenPayer

Diagnostic Testing of Common Sexually Transmitted Infections

Coverage criteria for STI diagnostic testing

Procedure and test codes

What providers must do

Background and rationale

Key definitions and abbreviations

Document history and references