Testing for herpes simplex virus (HSV) is complex, and results are not always a simple positive or negative. Incorrect results can lead to confusion and anxiety. Understanding the specific methods used to detect the virus or the body’s immune response is the first step in determining the reliability of any given test result. Questionable results often require further investigation, as some testing methods carry a known risk of producing inaccurate outcomes.
Understanding Herpes Testing Methods
Herpes testing falls into two categories: methods that look for the virus itself and methods that look for the body’s immune reaction. Direct viral detection tests, such as the Polymerase Chain Reaction (PCR) test or viral culture, require an active lesion or sore. The PCR test detects the virus’s genetic material and is considered highly accurate when a lesion is present.
When no visible sores are present, diagnosis relies on antibody testing performed via a blood sample. These tests detect Immunoglobulin G (IgG) antibodies, which the immune system produces in response to the virus and remain in the blood for life. Because they do not detect the virus directly, IgG tests are the primary source of diagnostic ambiguity. Testing for Immunoglobulin M (IgM) antibodies is not recommended for diagnosis because it is not type-specific and can produce misleading results.
The Reality of False Negative Results
A false negative occurs when the test indicates a person does not have herpes despite being infected. The most common cause in blood testing is the “window period.” After initial exposure, the body needs time to produce a detectable level of IgG antibodies, a process called seroconversion. This period can take anywhere from a few weeks to several months, meaning a test taken too early will miss the infection.
False negatives can also occur with direct viral detection tests, even during an active outbreak. A swab test, such as a viral culture, can be negative if the lesion is too old, already healing, or was not collected properly. The amount of active virus decreases rapidly as a lesion begins to crust over, increasing the chance of an inaccurate result if the sample is taken more than 48 hours after symptoms appear. Additionally, some IgG tests may be less sensitive in detecting low-titer antibody responses, which can occur with infections like HSV-1.
The Causes of False Positive Results
False positive results, where a person tests positive despite not having the infection, primarily stem from the limitations of commercial IgG antibody blood tests. The main issue is cross-reactivity, which happens when the antibodies the test detects react with proteins from other, similar viruses. Since HSV is part of the larger human herpesvirus family, antibodies against common viruses like HSV-1 or Varicella Zoster Virus (VZV, which causes chickenpox and shingles) can sometimes trigger a positive result for HSV-2.
The potential for a false positive is higher when the test yields a low index value. Commercial IgG tests report results using an index scale, where a value greater than 1.1 is considered positive. However, results in the low-positive range (generally between 1.1 and 3.5) have a much higher probability of being inaccurate. Studies have shown that for HSV-2, only about 50.7% of positive IgG tests in this low range were confirmed as true positives by more accurate methods.
This phenomenon relates to a test’s specificity, which is its ability to correctly identify people who do not have the disease. Standard screening tests are not 100% specific, and their accuracy decreases dramatically with low index values, especially in low-risk populations. For some commercially available HSV-2 tests, the specificity can be as low as 39.8% for index values between 1.1 and 2.9, meaning a significant number of positive results in this range are false.
Next Steps After a Questionable Result
When a test result is questionable, especially a low-positive IgG blood test result, confirmatory testing is advised. The most reliable method for confirming a diagnosis is the Western Blot test, which is regarded as the gold standard for type-specific antibody testing. Unlike commercial tests that look for a single protein, the Western Blot examines the full pattern of antibodies against multiple viral proteins, offering high sensitivity and specificity, often exceeding 99%.
If a person has a negative result but suspects recent exposure, retesting is necessary to rule out a false negative caused by testing too early. To ensure the window period has closed, it is recommended to wait 12 to 16 weeks from the last potential exposure before repeating the type-specific IgG test. A healthcare provider should interpret ambiguous results by factoring in the specific index value, the person’s symptoms, and their exposure history. Consulting a specialist can help determine the appropriate follow-up, which may include sending the sample for Western Blot confirmation.