Clinical Focus
Genital Herpes
Laboratory Support of Diagnosis and Management
Clinical background [return to contents]
Infection with herpes simplex virus type 2 (HSV-2), which most often causes genital herpes and its symptomatic recurrences, is common in the United States. Among people aged 14 to 49 years old, seroprevalence in 2015-2016 was 12% for HSV-2, but higher (35%) among non-Hispanic Black Americans.1 Type-1 HSV (HSV-1) most often causes oral herpes and has higher seroprevalence in the same age range (48%, notably 72% among Mexican Americans). However, HSV-1 is also responsible for an increasing proportion of primary genital infections. In some populations (eg, men who have sex with men [MSM], young women), HSV-1 has been reported to account for over half of genital herpes infections.2,3 Identification of HSV type can indicate the risk of disease recurrence and transmission.
Genital herpes may be associated with painful vesicular or ulcerative lesions affecting anogenital areas. However, most infections are transmitted by individuals who do not know they are infected because symptoms are often mild or absent.4 In rare cases, genital HSV infections can disseminate to other organs (eg, lungs or liver) or affect the central nervous system (CNS, eg, encephalitis). Pregnant individuals can also transmit HSV to neonates (ie, neonatal herpes), especially those who acquire genital herpes near the time of delivery.4
Diagnosing genital herpes can be difficult because typical lesions are often absent at the time of clinical visit (Figure 1).5,6 Many laboratory methods, such as nucleic acid amplification tests (NAATs), viral culture, and antibody (serologic) testing, are available to address this difficulty.
This Clinical Focus discusses the testing options available for the diagnosis and management of genital HSV infections. It is provided for informational purposes only and is not intended as medical advice. Test selection and interpretation, diagnosis, and patient management decisions should be based on the provider’s education, clinical expertise, and assessment of the patient.
Note that the CDC recommends offering HIV testing to individuals diagnosed with genital herpes.2 See HIV Infection: Laboratory Testing for Diagnosis and Management | Test Guide | Quest Diagnostics for more information on HIV testing options.
Other than genital herpes, syphilis also frequently causes anogenital ulcerative lesions in young people.4 See Syphilis: Laboratory Support for Screening, Diagnosis, and Monitoring | Clinical Focus | Quest Diagnostics for more information on syphilis testing options.
Individuals suitable for testing [return to contents]
NAAT testing may be appropriate for
- Individuals with mucocutaneous lesions associated with HSV infection4
- Adults or children with suspected HSV CNS infection4,7
- Neonates with suspected HSV infection4
Viral culture testing may be appropriate for
- Individuals with mucocutaneous lesions associated with HSV infection4
Type-specific serologic testing may be appropriate for
- Individuals who have recurrent or atypical genital symptoms4
- Individuals who have lesions with negative NAAT or viral culture results4
- Individuals who have a prior diagnosis of genital herpes without laboratory confirmation4
- Individuals who have a partner with genital herpes4
- Individuals at increased risk of HSV infection with a history of genital herpes symptoms (eg, those presenting for an evaluation for sexually transmitted infections [STIs], those with multiple sex partners or HIV infection, or MSM with previously undiagnosed genital tract infection)4
- Pregnant individuals at risk for HSV-2 infection4
Screening asymptomatic adolescents, adults, or pregnant individuals for HSV-1 or HSV-2 antibodies is not recommended.8
Test availability [return to contents]
Quest Diagnostics offers a variety of NAAT, viral culture, and serologic tests for HSV (Table).
Table. Tests Available for Diagnosis and Management of Herpes Simplex Virus Infection [return to contents]
Test code |
Test name |
Specimen type |
Clinical use |
Virologic |
|||
NAATs |
|||
Herpes Simplex Virus, Type 1 and 2 DNA, Qualitative, Real-Time PCRa |
Swab, CSF, serum, bronchial alveolar lavage, bronchial wash |
Diagnose HSV infection in neonates or infection affecting CNS or other systems; determine HSV type (this is not the preferred test for anogenital lesions, refer to test code 90570) |
|
Sexually-Transmitted Infections (STIs) Genital Lesion Panelb Includes herpes simplex virus, type 1 and 2 mRNA, TMA (test code 90570) and T pallidum DNA qualitative real-time PCR (test code 16595). |
Lesion swab |
Distinguish genital herpes from syphilis |
|
SureSwab ® Herpes Simplex Virus, Type 1 and 2 mRNA, TMA |
Anogenital lesion swab |
Diagnose HSV infection when lesions are present; determine HSV type |
|
Culture |
|||
Herpes Simplex Virus Culture with Reflex to Typingb,c Includes HSV culture (test code 2692) with reflex to typing (test code 90820) if culture is positive. |
Swab, lesion (vesicle) aspirate, bronchial or nasopharyngeal lavage, biopsy |
Diagnose HSV infection when lesions are present; determine HSV type |
|
Serologic |
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Herpes Simplex Virus 1 and 2 (IgG), with Reflex to HSV-2 Inhibitionc,d |
Serum |
Determine serostatus for HSV-1; diagnose and confirm HSV-2 infection when lesions are absent in individuals with risk factors |
|
Herpes Simplex Virus 2 (IgG), with Reflex to HSV-2 Inhibitionc,d |
Serum |
Diagnose and confirm HSV-2 infection when lesions are absent in individuals with risk factors |
|
| CNS, central nervous system; CSF, cerebrospinal fluid; HSV, herpes simplex virus; NAATs, nucleic acid amplification tests; PCR, polymerase chain reaction; STIs, sexually transmitted infections; TMA, transcription-mediated amplification. | |
| a | This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the US Food and Drug Administration. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes. |
| b | Panel components may be ordered separately. |
| c | Reflex testing performed at an additional charge with an additional CPT ® code. |
| d | False positive HSV-2 results can occur especially at low index values (1.1-3.0). Therefore, positive HSV-2 IgG results with index values between 1.1 to 6.0 will reflex to HSV-2 IgG inhibition test. |
Test selection and interpretation [return to contents]
Diagnosis
Most HSV infections are asymptomatic or unrecognized, but symptoms of genital herpes including painful blisters or ulcers can recur over time. Thus, the Centers for Disease Control and Prevention (CDC) recommends laboratory confirmation of infection in appropriate individuals (See “Individuals suitable for testing” section).4 The appropriate test depends largely on the presence or absence of lesions (Figures 1 and 2).4
Virologic testing
When genital or mucocutaneous lesions are present, NAATs or viral culture from the lesions are recommended.4
NAATs are highly sensitive (91%-100%) and preferred for diagnosing herpes. PCR is the test of choice for CNS or systemic infections.4,9 Testing the blood using PCR for genital infections is not recommended unless a disseminated infection is suspected.4 Quest offers a NAAT (test code 90570) that is approved by the US Food and Drug Administration (FDA) for detecting HSV-1 and HSV-2 from anogenital lesions. In the absence of lesions, anogenital swabs should not be used to screen for HSV infection.4 Quest also offers a NAAT panel (test code 38286) for the differential diagnosis of HSV and Treponema pallidum infections, the 2 most common causes of anogenital ulcerative lesions in young people. Another NAAT (test code 34257) may be used for detecting HSV-1 and HSV-2 from other specimen types using polymerase chain reaction (PCR) if clinically indicated.4
Viral culture has low sensitivity that decreases as lesions heal (95% for vesicular lesions, 70% for ulcerative lesions, and 25% for crusted lesions); sensitivity is especially low for recurrent lesions.4,6 If HSV is detected, the type of HSV should be identified.4 Quest offers viral culture tests with typing (test code 2649).
A “detected” result for NAATs or “isolated” result for viral culture supports the diagnosis of HSV infection.
A “not detected” result for NAATs or “not isolated” result for viral culture does not exclude the possibility of HSV infection. In the absence of a lesion, viral shedding is intermittent. Therefore, genital swabs collected in the absence of lesions are not recommended for testing.4 Viral culture can also have lower sensitivity if the specimen is collected from healing ulcers or is improperly collected.
Serologic testing
When exposure to HSV is suspected but lesions are absent, type-specific serologic tests (test code 17169) for HSV antibodies can help diagnose HSV infection.4 Type-specific antibodies are detectable an average of 2 to 3 weeks after primary infection but may take up to 3 to 6 months to develop (Figure 1).5,10 Because antibodies to HSV persist for life, serologic assays can detect past HSV infection. Serologic testing is not recommended for neonates.9
A type-specific HSV-1 serologic test alone does not determine the site of infection because HSV-1 infection can be acquired during childhood.4 On the contrary, the presence of type-specific HSV-2 antibodies indicates anogenital infection because HSV-2 infection is nearly always sexually transmitted.4 A type-specific HSV-2 test (test code 17170) is recommended for individuals with HIV infection, especially those with a history of genital infection.4
The CDC recommends against using immunoglobulin M (IgM) testing for HSV owing to the drawbacks: IgM tests (1) cannot distinguish between primary HSV infection and recurrent genital or oral episodes and (2) cannot differentiate HSV types.4
A positive IgG result indicates the presence of detectable antibody to the corresponding virus (HSV-1 or HSV-2), which indicates current or previous exposure to the virus. Sensitivity and specificity for detecting HSV-1 IgG are relatively low compared to HSV-2 (92% and 89% vs 95% and 94%).11 Therefore, virologic tests are recommended to confirm HSV-1 infection.4 Positive predictive value for HSV-2 IgG is low (69%),11 which is one reason that screening of asymptomatic persons is not recommended.8 The CDC recommends HSV-2 confirmatory tests for low-index results by enzyme immunoassays.4 Quest offers an HSV-2 inhibition study for results with an index ≥6.0 as reflex testing to confirm the presence of HSV-2 IgG.
A negative result suggests absence of infection. However, a negative result does not rule out infection. False-negative results occur in 12% to 30% of patients.12 Antibodies often are not detected during early infection. If clinical suspicion of genital HSV infection is high, then repeat antibody testing should be considered 4 to 12 weeks later.4
References [return to contents]
- McQuillan G, Kruszon-Moran D, Flagg EW, et al. Prevalence of herpes simplex virus type 1 and type 2 in persons aged 14-49: United States, 2015-2016. NCHS data brief. 2018;(304):1-8.
- Bernstein DI, Bellamy AR, Hook EW, et al. Epidemiology, clinical presentation, and antibody response to primary Infection with herpes simplex virus type 1 and type 2 in young women. Clin Infect Dis. 2013;56(3):344-351. doi:10.1093/cid/cis891
- Ryder N, Jin F, McNulty AM, et al. Increasing role of herpes simplex virus type 1 in first-episode anogenital herpes in heterosexual women and younger men who have sex with men, 1992–2006. Sex Transm Infect. 2009;85(6):416. doi:10.1136/sti.2008.033902
- Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1-187. doi:10.15585/mmwr.rr7004a1
- Gupta R, Warren T, Wald A. Genital herpes. Lancet. 2007;370(9605):2127-2137. doi:10.1016/s0140-6736(07)61908-4
- Kimberlin DW, Rouse DJ. Genital herpes. N Engl J Med. 2004;350(19):1970-1977. doi:10.1056/nejmcp023065
- Venkatesan A, Tunkel AR, Bloch KC, et al. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the International Encephalitis Consortium. Clin Infect Dis. 2013;57(8):1114-1128. doi:10.1093/cid/cit458
- US Preventive Services Task Force, Mangione CM, Barry MJ, et al. Serologic screening for genital herpes infection. JAMA. 2023;329(6):502-507. doi:10.1001/jama.2023.0057
- Committee on Infectious Diseases American Academy of Pediatrics. Herpes simplex. In: Kimberlin DW, Banerjee R, Barnett ED, et al., eds. Red Book: 2024–2027 Report of the Committee on Infectious Diseases. 33rd ed. American Academy of Pediatrics; 2024:467-478. doi:10.1542/9781610027373-s3_008_012
- Strick LB, Wald A. Diagnostics for herpes simplex virus: is PCR the new gold standard? Mol Diagn Ther. 2006;10(1):17-28. doi:10.1007/bf03256439
- Crawford KHD, Selke S, Pepper G, et al. Performance characteristics of highly automated HSV-1 and HSV-2 IgG testing. J Clin Microbiol. 2024;62(6):e00263-24. doi:10.1128/jcm.00263-24
- Rooijen MS van, Roest W, Hansen G, et al. False-negative type-specific glycoprotein G antibody responses in STI clinic patients with recurrent HSV-1 or HSV-2 DNA positive genital herpes, The Netherlands. Sex Transm Infect. 2016;92(4):257. doi:10.1136/sextrans-2015-052213
Content reviewed 6/2025
17169 - Herpes Simplex Virus 1 and 2 (IgG), with Reflex to HSV-2 Inhibition
34257 - Herpes Simplex Virus, Type 1 and 2 DNA, Qualitative, Real-Time PCR
90570 - SureSwab®, Herpes Simplex Virus, Type 1 and 2 mRNA,TMA
2649 - Herpes Simplex Virus Culture with Reflex Typing
17170 - Herpes Simplex Virus 2 (IgG), with Reflex to HSV-2 Inhibition
38286 - Sexually-Transmitted Infections (STIs) Genital Lesion Panel
Sexually Transmitted Infections Associated With Urethritis, Cervicitis, and PID
Reference ranges are provided as general guidance only. To interpret test results use the reference range in the laboratory report.
The tests listed by specialty and category are a select group of tests offered. For a complete list of Quest Diagnostics tests, please adjust the filter options chosen, or refer to our Directory of Services.