A positive result on a medical screening test can feel alarming, especially when the test identifies a lifelong condition like herpes simplex virus (HSV). A false positive result occurs when a test indicates a person has an infection, such as HSV-1 or HSV-2, when the virus is not actually present. Understanding the technical reasons behind these inaccurate readings can help reduce anxiety and guide the necessary next steps. The reliability of HSV testing depends heavily on the type of test used and the biological factors within an individual’s immune system.
Antibody Testing and Specificity Limitations
The test most frequently associated with false positive results is the blood test, known as a serology or antibody test, which primarily detects Immunoglobulin G (IgG) antibodies. This screening method measures the body’s long-term immune response, indicating the immune system has been exposed to the virus at some point. A test’s accuracy is measured by its specificity—its ability to correctly identify individuals who do not have the infection. Standard commercial HSV antibody tests lack perfect specificity, meaning they can sometimes react to substances other than the target virus. This limitation is particularly notable for HSV-2 tests, where the specificity of some common commercial tests is not high enough to be relied upon without further confirmation.
Cross-Reactivity with Other Viral Infections
The primary biological cause of a false positive result in HSV serology is a phenomenon called cross-reactivity. This happens when antibodies produced in response to one type of virus mistakenly bind to the proteins of a different, but structurally similar, virus during the test process. Modern type-specific HSV tests target antibodies against Glycoprotein G (gG), with gG-1 distinguishing HSV-1 and gG-2 distinguishing HSV-2.
However, the herpes virus family is large, and its members share structural similarity. Antibodies from other common human herpesviruses, such as Varicella Zoster Virus (VZV) or Cytomegalovirus (CMV), may weakly recognize and bind to the HSV gG protein. In the case of HSV-2 testing, the presence of HSV-1 antibodies can also lead to a false positive reading. If a person has a genuine HSV-1 infection, their antibodies may weakly react to the HSV-2 gG-2 antigen, resulting in a false positive HSV-2 result. This limitation underscores why a positive result, especially a low-level one, must be viewed with caution.
Interpretation Challenges from Low Index Values
The quantitative nature of the antibody test provides a numerical result called an index value, which is a key factor in determining the likelihood of a false positive. Most commercial HSV IgG tests report any index value of 1.1 or greater as a positive result. However, experts have noted that results falling just above this threshold are often unreliable and are considered to be in a “grey zone.” This low positive range is generally defined as index values between 1.1 and 3.5, though the exact range can vary by laboratory.
Results within this range represent a low concentration of antibodies, which are often non-specific or due to cross-reactivity. Studies have shown that when a person tests positive for HSV-2 with an index value in this low range, there is a high chance that the result is a false positive. For individuals with low index values and no history of symptoms, the probability of a false positive can be higher than 50% for HSV-2. This low index value indicates an ambiguous result, meaning a single positive screening test alone is insufficient for diagnosis, particularly when the value is close to the cutoff.
Confirmatory Testing and Next Steps
For anyone receiving a positive result, especially a low index value, the recommended next step is confirmatory testing to resolve the ambiguity. This two-step testing process involves following the initial screening result with a more definitive assay. The gold standard for confirmation is the Western Blot test, which offers significantly higher specificity than commercial screening tests. The Western Blot achieves greater accuracy by separating viral proteins and detecting a wider range of antibodies against multiple HSV proteins, not just the single gG protein.
This comprehensive analysis allows it to definitively differentiate between genuine HSV antibodies and those resulting from cross-reactivity. While the Western Blot is highly accurate, it is not widely available and must be ordered through specialized laboratories. Another option is to retest using the same commercial assay, typically 12 weeks after the initial test. If the initial result was a false positive, the index value will likely remain low or drop back to negative; a true positive result would typically increase significantly. A healthcare provider should guide the selection of the confirmatory test and interpret the results alongside the individual’s clinical history.