What diagnostic tests are available for genital herpes?
Most HSV infections are clinically silent. Therefore, laboratory tests are required to diagnose the infection. Even if symptoms are present, diagnoses based only on clinical presentation have a 20% false-positive rate. Always confirm diagnosis by laboratory assay.9 Furthermore, couples that are discordant for HSV-2 by history are often concordant by serologic assays, as the transmission already has occurred but was not recognized. In these cases, the direction of transmission cannot be determined, and stable couples often experience relief learning that they are not discordant.
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Several laboratory tools for HSV diagnosis based on direct viral detection and antibody detection can be used in clinical settings (TABLE 2). Among patients with symptomatic genital herpes, a sample from the lesion can be used to confirm and identify viral type. Because polymerase chain reaction (PCR) is substantially more sensitive than viral culture and increasingly available it has emerged as the preferred test.9 Viral culture is highly specific (>99%), but sensitivity varies according to collection technique and stage of the lesions. (The test is less sensitive when lesions are healing.)9,10 Antigen detection by immunofluorescence (direct fluorescent antibody) detects HSV from active lesions with high specificity, but sensitivity is low. Cytologic identification of infected cells (using Tzanck or Pap test) has limited utility for diagnosis due to low sensitivity and specificity.9
Type-specific antibodies to HSV develop during the first several weeks after acquisition and persist indefinitely.11 Most accurate type-specific serologic tests are based on detection of glycoprotein G1 and glycoprotein G2 for HSV-1 and HSV-2, respectively.
HerpeSelect HSV-2 enzyme immunoassay (EIA) is one of the most commonly used tests in the United States. The manufacturer considers results with index values 1.1 or greater as showing HSV-2 infection. Unfortunately, low positive results, often with a defined index value of 1.1 to 3.5, are frequently false positive. These low positive values should be confirmed with another test, such as Western blot.9
Western blot has been considered the gold standard assay for HSV-1 and HSV-2 antibody detection; this test is available at the University of Washington in Seattle. When comparing the HSV-1 EIA and HSV-2 EIA with the Western blot assay in clinical practice, the estimated sensitivity and specificity are 70.2% and 91.6%, respectively, for HSV-1 and 91.9% and 57.4%, respectively, for HSV-2.12
HerpeSelect HSV-2 Immunoblot testing should not be considered as confirmatory because this assay detects the same antigen as the HSV-2 EIA. Serologic tests based on detection of HSV-IgM should not be used for diagnosis of genital herpes as IgM response can present during a new infection or HSV reactivation and because IgM responses are not type-specific. Clearly, more accurate commercial type-specific antibody tests are needed.
Specific HSV antibodies can take up to 12 weeks to develop. Therefore, repeat serologic testing for patients in whom initial HSV antibody results are negative yet recent genital herpes acquisition is suspected.11 A confirmed positive HSV-2 antibody test indicates anogenital infection, even in a person who lacks genital symptoms. This finding became evident through a study of 53 HSV-2 seropositive patients who lacked a history of genital herpes. Patients were followed for 3 months, and all but 1 developed either virologic or clinical (or both) evidence of genital herpes.13
In the absence of genital or orolabial symptoms among individuals with positive HSV-1, serologic testing cannot distinguish anogenital from orolabial infection. Most of these infections may represent oral HSV-1 infection; however, given increasing occurrence of genital HSV-1 infection, this could also represent a genital infection.
What are the clinical uses of type-specific HSV serology?
Type-specific serologic tests are helpful in diagnosing patients with atypical or asymptomatic infection and managing the care of persons whose sex partners have genital herpes. Serologic testing can be useful to confirm a clinical diagnosis of HSV, to determine whether atypical lesions or symptoms are attributable to HSV, and as part of evaluation for sexually transmitted diseases in select patients. Screening for HSV-1 and HSV-2 in the general population is not supported by the Centers for Disease Control and Prevention (CDC) or the US Preventive Services Task Force (USPSTF) for several reasons9,10:
- suboptimal performance of commercial HSV antibody tests
- low positive predictive value of these tests in low prevalence HSV settings
- lack of widely available confirmatory testing
- lack of cost-effectiveness
- potential for psychological harm.