Diagnostic Testing for Herpes Simplex Virus Type 2 (HSV-2)

Testing Strategy Based on Clinical Presentation

For active genital lesions, the American College of Physicians recommends using nucleic acid amplification testing (NAAT/PCR) from the lesion as the first-line diagnostic test, with sensitivity and specificity exceeding 90% for most FDA-approved assays 1
The Centers for Disease Control and Prevention (CDC) suggests that NAAT/PCR is the preferred diagnostic test for detecting HSV-2 from genital ulcers or lesions, offering 11-71% superior sensitivity compared to viral culture 1
When no lesions are present, the CDC recommends using type-specific serological testing with glycoprotein G-based assays on venous blood samples, which have approximately 97% sensitivity and 98% specificity for detecting HSV-2 antibodies 2

The index value reported for HSV-2 serological tests is crucial, with values <0.9 considered negative, 0.9-1.1 considered indeterminate, 1.1-2.9 considered positive with 39.8% specificity, and ≥3.0 considered positive with 78.6% specificity 1
For low positive results (index value <3.0), the CDC recommends confirming with a second test using a different glycoprotein G antigen to avoid false-positive results 2

The US Preventive Services Task Force recommends against screening for HSV-2 infection among asymptomatic adolescents and adults, but suggests testing for pregnant women at risk, men who have sex with men, people who are HIV positive, and sexual partners of individuals with known genital herpes 2

The American College of Physicians recommends using assays that differentiate between HSV-1 and HSV-2 to provide accurate prognostic information, as HSV-2 causes more frequent recurrences and subclinical viral shedding compared to HSV-1 genital infections 1