By Kathleen M. Murphy, Ph.D & Kenneth E. Youens, M.D.
Genital herpes virus (HSV) infection, the most frequent sexually transmitted disease worldwide, is estimated to affect over one million new American women each year (1). People with genital HSV infection can develop recurrent and painful genital and perineal lesions with considerable associated psychosocial distress. In pregnancy, vertical transmission of HSV from mother to fetus can result in serious neonatal morbidity or even death (2).
Though HSV type 2 (HSV-2) has historically accounted for the majority of genital herpes infections (between 7090%), recent studies indicate an increase in genital infections caused by HSV type 1 (HSV-1). HSV-1 is now believed to cause between 10-30% of cases of genital herpes, including over half of first episodes (2). Prior or current infection with HSV-1 provides limited protection against HSV-2, though previously infected women remain at risk for new infections (2). Although the prognoses for HSV-1 and HSV-2 differ (see table), infections caused by HSV-1 and HSV-2 cannot be distinguished on clinical grounds alone. Laboratory testing is necessary to confirm the diagnosis and to distinguish between the two viruses.
Laboratory Testing
A diagnosis of genital herpes infection should be confirmed by laboratory testing, since various causes of genital ulcers can have a similar clinical presentation. There are three primary methods of testing: serological testing, viral culture, and nucleic acid-based testing (PCR).
Serological testing involves the specific detection of anti-HSV-1 or anti-HSV-2 IgG (and sometimes IgM) antibodies in the blood. Serological testing is highly sensitive, and can be effective for distinguishing acute from chronic HSV infection. However, since by age 40 as many as 20% of women are seropositive for HSV-2 and up to 70% United States adults are HSV-1 seropositive, a significant drawback to serological testing is that it cannot distinguish clinically significant chronic infections from latent infections that occurred in the remote past. Also, since genital and oral infections can both be caused by either HSV-1 or HSV-2, an additional drawback is that serological testing cannot specifically identify genital infections.
Viral culture has traditionally been considered the diagnostic gold-standard, but is time consuming, requires specialized specimen transport, is labor intensive, and may take up to ten days to yield a result. In addition, its sensitivity, particularly for recurrent or healing lesions, can be as low as 25%.
PCR-based testing is more specific for clinically significant HSV infection than serology, because it can definitively identify active genital lesions, regardless of HSV type. PCR-based methods are potentially much faster than viral culture, and specimen preservation and transport is simpler. PCR is more sensitive than culture for detecting HSV infections, both in women with active lesions and for detecting asymptomatic shedding in the absence of a clinically apparent lesion (4).
ProPath HSV Real-Time PCR Assay
Description: This assay simultaneously detects and differentiates HSV-1 and HSV-2 using real-time PCR technology. An internal control is built into the assay to determine adequacy of the specimen. PCR is more sensitive than culture, and more specific than serology for the detection and differentiation of clinically significant HSV-1 and HSV-2 infections. Note that a negative result does not eliminate the possibility of latent HSV infection.
Method: TaqMan Real Time Polymerase Chain Reaction( PCR) – Qualitative
Specimens: ThinPrep and SurePath liquid cytology specimens
References:
1. Robboy SJ, Bentley RC, Russell P, Anderson MC, Mutter GL, Prat J. Robboy’s Pathology of the Female Reproductive Tract. 2nd ed. Churchill Livingstone; 2008.
2. Gupta R, Warren T, Wald A. Genital herpes. Lancet. 2007;370(9605):2127-37.
3. Brown Z a, Wald A, Morrow RA, et al. Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant. JAMA: the journal of the American Medical Association. 2003;289(2):203-9.
4. Aumakhan B, Hardick A, Quinn TC, et al. Genital herpes evaluation by quantitative TaqMan PCR: correlating single detection and quantity of HSV-2 DNA in cervicovaginal lavage fluids with cross-setional and longitudinal clinical data. Virology journal. 2010;7(1):328.