Background: Herpes Simplex Virus (HSV) is a common and prevalent sexually transmitted infection affecting 6 billion people globally. Serological screening for HSV in asymptomatic individuals is not recommended because of suboptimal test performance characteristics. We reviewed the performance of serologic screening in real-world populations, which included symptomatic and asymptomatic individuals, and compared findings to publicly available product package insert data in currently used US Food and Drug Administration (FDA) cleared HSV-2 serologic tests.
Methods: Applying no date or geographical restrictions, we searched PubMed and Google Scholar to identify human studies reporting performance of Herpes Simplex Type-2 antibody tests compared to the University of Washington Western Blot HSV-2 assay. We reviewed regulatory data, which included data from the US FDA 510(k) premarket submissions from test manufacturers reported in package inserts.
Results: We identified 12 published studies relevant to the research question (N=8087 test results). Assays evaluated included ELISA (enzyme-linked immunoassay) and immunoblot.
Real-world performance values compared to the UW HSV-2 Western Blot for the Focus HerpeSelect HSV-2 ELISA ranged in sensitivity from 91.9% to 100.0% and specificity 41.0% to 97.8%. For the Biokit HSV-2 Rapid ELISA, sensitivity was 66.0% and specificity 90.9%. For the Virotech Line Immunoblot, sensitivity was 98.1% and specificity 100.0%
In comparison, package insert data for the Focus HerpeSelect HSV-2 ELISA had sensitivity of 96.1% and specificity of 97.0%, Biokit HSV-2 Rapid ELISA 92.2% and 87.0%, and Virotech Line Immunoblot 91.6% and 94.9%.
In 7 studies including African populations (N=5293 test results), Focus HerpeSelect sensitivity ranged from 98.0% to 100.0% and specificity from 41.0% to 97.5%. In 5 studies that excluded African populations (N=2794 test results), Focus HerpeSelect performance ranged from sensitivity of 91.9% to 100.0% and specificity of 57.4% to 100.0%. One study was excluded to account for bias. In the remaining 4 studies that excluded African populations (N=1930 test results), the Focus HerpeSelect specificity ranged from 89.0% to 100.0%.
Conclusion: HSV-2 serological test performance demonstrated discrepancies between real-world studies and reported data in manufacturers’ package inserts. Test performance may vary by study populations. Larger, independent, and more robust studies of HSV-2 antibody test performance are needed.
