Can a urine test be used to diagnose Herpes Simplex Virus (HSV) infection?

Can Urine Be Used to Test for HSV?

Urine testing for HSV is NOT a standard or recommended diagnostic approach for genital herpes, and should only be used via NAAT/PCR in very specific circumstances when other sampling methods are not feasible.

Standard Diagnostic Approach for HSV

The optimal diagnostic strategy depends entirely on whether active lesions are present:

When Active Lesions Are Present

• NAAT/PCR from lesion swabs is the gold standard, with sensitivity 11-71% superior to viral culture and >90% sensitivity and specificity for most FDA-approved assays 1
• Samples should be collected by opening vesicles with a sterile needle and swabbing the vesicular fluid, or swabbing the base of ulcers 1
• Viral culture is acceptable if NAAT is unavailable due to cost or laboratory constraints, though it has lower sensitivity (90% for fresh vesicles, dropping to 27% for crusting lesions) 1, 2
• Type-specific testing to differentiate HSV-1 from HSV-2 is essential for prognosis and counseling, as genital HSV-1 has fewer recurrences and less subclinical shedding than HSV-2 1, 3

When No Active Lesions Are Present

• Type-specific serologic testing (glycoprotein G-based assays) is the ONLY appropriate test, as viral detection methods should never be performed without active lesions due to intermittent viral shedding 1, 4
• HSV-2 serology has approximately 92% sensitivity but significant specificity problems: index values 1.1-2.9 have only 39.8% specificity (60% false positives), while values ≥3.0 have 78.6% specificity 1, 4
• Low positive results (index value <3.0) should be confirmed with a second assay using different glycoprotein G antigen 1, 4
• Allow 12 weeks after potential exposure before testing to avoid false negatives during the antibody window period 1, 4

The Limited Role of Urine Testing

According to European guidelines, urine can be tested via NAAT for HSV in both men and women, but this is listed as an alternative sampling site, not a preferred method 1:

• Urine testing is mentioned only in the context of urethral involvement when direct urethral swabs cannot be obtained 1
• The preferred approach for urethral HSV in males is inserting a swab 0.5-2 cm into the urethral meatus to collect exudates directly 1
• For females with urethral involvement, a swab inserted 0.5 cm into the urethra is preferred 1

Critical Pitfalls to Avoid

• Never use HSV molecular assays in the absence of genital ulcers—the intermittent nature of HSV shedding makes this approach insensitive and unreliable 1
• Do not rely on Tzanck smear or direct immunofluorescence assay, as these lack adequate sensitivity 1
• Do not test for HSV IgM antibodies, as approximately one-third of patients with recurrent HSV-2 have IgM responses, making it a poor indicator of recent infection 1, 4
• Patients with HSV-1 infection are more likely to have false-positive HSV-2 serologic tests, particularly with low index values 1, 4

Practical Algorithm

1. Patient presents with genital lesions: Swab lesion for NAAT/PCR (or culture if NAAT unavailable) 1, 3
2. Patient presents without lesions but suspects HSV: Order type-specific HSV serology (IgG only) 1, 4
3. Urine testing: Reserve only for situations where urethral involvement is suspected but direct urethral swabbing is not feasible 1