Can laboratory tests be negative for a female patient with a history of genital herpes if no lesion is present?

Laboratory Testing for Genital Herpes Without Active Lesions

Yes, laboratory tests can be negative when no lesion is present if you're using the wrong test—viral detection tests (PCR/culture) should never be performed without active lesions, but type-specific serologic antibody testing is the appropriate test for diagnosing genital herpes in patients without current lesions. 1

The Critical Distinction: Which Test for Which Situation

When NO Lesion is Present (Your Scenario)

Type-specific serologic testing (HSV-2 IgG antibody test) is the only appropriate laboratory test when no active lesion is present. 1, 2

• Viral detection methods (PCR/NAAT or culture) should NOT be obtained in the absence of genital ulcers because HSV shedding is intermittent, making swabs obtained without lesions insensitive and unreliable 1
• Serologic testing detects antibodies that develop after infection and persist indefinitely, indicating past exposure and ongoing latent infection 3, 4
• The sensitivity of HSV-2 serologic testing is approximately 92%, with specificity around 97-98% when using glycoprotein G-based assays 1, 3

When an Active Lesion IS Present

• PCR/NAAT from the lesion is first-line, with >90% sensitivity and specificity 1, 2
• Viral culture is second-line if PCR unavailable, though significantly less sensitive 1, 2

Important Caveats About Serologic Testing

The Window Period Problem

A negative serologic test can occur if testing is performed too early after infection—antibodies may take up to 12 weeks to develop. 1, 3

• If recent acquisition is suspected and the test is negative, repeat testing after 12 weeks is necessary 3, 4
• This represents a true false-negative during the "window period" 1

The False-Positive Problem with Low Index Values

HSV-2 serologic tests have serious specificity limitations, particularly with low positive results. 1

• Index values of 1.1-2.9 have only 39.8% specificity (meaning 60% are false positives) 1
• Index values ≥3.0 have 78.6% specificity (still 21% false positives) 1
• Patients with HSV-1 infection are more likely to have false-positive HSV-2 tests with low index values 1
• For low positive results (index value <3.0), confirmation with a second test using different methodology is recommended 3, 4

The False-Negative Problem with HSV-1 Serology

HSV-1 serologic assays lack sensitivity, with only 70.2% sensitivity in one study, resulting in false-negative diagnoses. 1

Clinical Algorithm for Your Patient

For a female patient with history of genital herpes but no current lesion:

1. Order type-specific HSV-2 IgG serology (glycoprotein G-based assay) 2, 3
2. Do NOT order PCR or viral culture without an active lesion 1
3. Interpret results carefully:
   • Negative result: Could be true negative OR window period if recent exposure (repeat in 12 weeks if suspected recent infection) 3, 4
   • Positive with index value <3.0: Consider confirmatory testing with different assay 3, 4
   • Positive with index value ≥3.0: More reliable, indicates past HSV-2 infection 1

Why This Matters for Patient Care

Most genital herpes (80-90%) progresses subclinically, and many patients have asymptomatic viral shedding without recognizing symptoms. 1

• Type-specific serology can identify these asymptomatic infections, which is important since transmission often occurs during asymptomatic periods 2
• A study of 779 women found that 58% with HSV-2 antibodies had neither viral shedding nor history of clinical episodes at the time of testing 5
• Only 22% of women with evidence of HSV-2 infection had symptoms 5

The bottom line: Laboratory tests can absolutely be negative when no lesion is present if you use viral detection methods (which you shouldn't), but serologic testing is specifically designed for this scenario and will detect past infection regardless of current lesion status—though you must account for the window period and false-positive/false-negative limitations described above.