Making the diagnosis

The FDA recently approved HSV DNA assays for use with samples collected from anogenital lesions. These new DNA tests are highly sensitive and accurately distinguish between HSV-1 and HSV-2. Visit the FDA website for more information on these tests.

Swab Viral Tests (Viral Culture and PCR)

Positive: Swab tests have the advantage of identifying both anatomic location of the infection and viral type (though typing often needs to be specifically requested). A genital culture positive for HSV-1, for example, provides definitive diagnosis of genital herpes due to HSV-1. HSV-1 has been increasing as a cause of first episodes of genital herpes. Serologic testing is not necessary in a patient with a recurrent genital lesion who has a prior positive HSV culture that has been typed.

Negative: Swab test results may be negative for many reasons. A negative swab test does not rule out genital herpes.4 Sensitive swab tests performed early in the next suspected outbreak or type-specific serologic testing may be useful 6-12 weeks after the most recent exposure.12

Serologic Tests for HSV-2

HSV-2 Positive: A positive test for HSV-2 indicates genital infection, as orolabial infection alone is rarely due to HSV-2. Patients who are diagnosed by serologic testing but have no symptoms should be educated about mild, often unrecognized, symptomatic genital herpes disease, asymptomatic viral shedding, and risk of transmission to uninfected sex partners. Confirmatory or repeat testing is usually not necessary, unless, for example, the ELISA value is a low positive in the absence of symptoms. There are various definitions for what constitutes a low positive value, depending on the particular serologic test.

HSV-2 Equivocal: An equivocal result may be resolved by repeat testing with a second specimen collected one month after the initial specimen. If repeating the original serologic test does not resolve the equivocal result, then a confirmatory test should be considered. Rarely, seroconversion can take as long as 6 months after acquisition of infection. 

HSV-2 Negative: A negative serologic test for HSV-2 usually means no HSV-2 infection, unless the infection was acquired recently. Because some people can take months to seroconvert, these results should be interpreted cautiously in someone with recent exposure, high-risk behavior, or a new lesion. A repeat test 3-4 months after the initial test may be helpful.

Serologic Tests for HSV-1

HSV-1 Positive: Slightly more than half of U.S. adults have antibody to HSV-1, so a positive test is not unusual nor does it imply genital herpes, since most people with HSV-1 antibodies have orolabial infection (“cold sores” or “fever blisters”). However, an increasing percentage of new genital herpes infections in young adults appear to be caused by HSV-1.6 A person with no history of cold sores who has a positive HSV-1 antibody test cannot know for certain where they are infected. These patients should be told that if they develop signs or symptoms in either the oral or genital area, they should come into the office for an evaluation to determine if these are herpetic.

HSV-1 Equivocal: An equivocal result may be resolved by repeat testing with a second specimen collected one month after the initial specimen. If repeating the original serologic test does not resolve the diagnosis, then a confirmatory test should be considered. 

HSV-1 Negative: A negative serologic test for HSV-1 usually means no infection with HSV-1 unless it was acquired recently. Of note, the sensitivity of the Focus HSV-1 ELISA is slightly lower than that of the HSV-2 assay, so the ELISA test may miss almost 1 out of 10 people infected with HSV-1.13 New acquisition of genital HSV-1 infection is of particular concern for pregnant women without HSV-1 antibodies due to high risk of vertical transmission to the neonate.