Serologic Screening for Genital Herpes

Abstract

This systematic review to support the 2023 US Preventive Services Task Force Recommendation Statement on serologic screening for genital herpes summarizes published evidence on the benefits and harms of screening and interventions for genital herpes in asymptomatic sexually active adolescents, adults, and pregnant persons with no clinical history of genital herpes.

Genital herpes is a viral sexually transmitted infection (STI) caused by 1 of 2 herpes simplex virus (HSV) subtypes: HSV-1 or HSV-2. HSV-1 can cause infection at either the orofacial (eg, cold sores) or anogenital region, whereas HSV-2 infection is typically limited to the anogenital region.¹ In asymptomatic, seropositive persons who have never knowingly experienced an HSV outbreak, HSV-1 serology cannot predict the future outbreak site. Therefore, serologic screening for genital herpes is limited to HSV-2 only.

Genital herpes is one of the most prevalent STIs in the US and can lead to both acute and chronic morbidity in adolescents and adults, as well as significant morbidity and mortality in neonates.¹ In theory, early identification of unrecognized HSV-2 infection, followed by appropriate counseling or treatment, could reduce transmission to sexual partners and neonates as well as reduce morbidity from symptomatic recurrence.¹

In 2016, the US Preventive Services Task Force (USPSTF) recommended against routine serologic screening for genital herpes infection in asymptomatic adolescents and adults, including those who are pregnant (D recommendation).² This limited evidence update aimed to identify studies published since the previous (2016) evidence review³ conducted for the USPSTF to inform an updated recommendation.

Methods

A literature search of PubMed/MEDLINE, the Cochrane Library, EMBASE, and trial registries was conducted for studies from September 30, 2015, through January 16, 2022. Additional sources included reference lists of retrieved articles, outside experts, and public commenters, with ongoing surveillance of the literature through July 22, 2022. Two investigators independently evaluated the eligibility of all abstracts and articles and rated study quality using predefined criteria.² An analytic framework and 7 key questions (KQs) guided the evidence update (Figure). Detailed methods and results are available in the full evidence report.¹

Figure. Analytic Framework: Serologic Screening for Genital Herpes.

HSV-1 and HSV-2 indicate herpes simplex virus 1 and herpes simplex virus 2, respectively; KQ, key question.

^aStudies that screened using an HSV-2 serologic test alone or a type-specific serologic test for both HSV-1 and HSV-2 simultaneously were included if they met other eligibility criteria; however, only the accuracy of test characteristics related to HSV-2 serologic tests was evaluated.

^bKQ7 was only addressed if the literature for KQs 1 and 5 was insufficient, but the literature for KQ4 was sufficient. Evidence reviews for the US Preventive Services Task Force (USPSTF) use an analytic framework to visually display the KQs that the review will address to allow the USPSTF to evaluate the effectiveness and safety of a preventive service. The questions are depicted by linkages that relate to interventions and outcomes. Further details are available from the USPSTF procedure manual.⁴

For purposes of this review, the term asymptomatic refers to individuals with no known past or current history of genital herpes, which may include individuals with unrecognized genital herpes because symptoms either were very mild or were attributed to other causes (eg, urinary tract infection). Studies of individuals previously diagnosed with genital herpes who are not currently experiencing symptoms (ie, an asymptomatic period following an outbreak of genital herpes) were not considered eligible for this review. Studies of persons with HIV or other immunosuppressive conditions were also not eligible for this review.

Results

We reviewed 3119 abstracts and 64 full-text articles. No new eligible studies were identified for any KQ. We identified 1 new diagnostic test accuracy study (KQ2), which was excluded because of poor study quality.

Discussion

This systematic review yielded no new eligible studies published since the 2016 recommendation against screening for genital herpes in asymptomatic persons. Therefore, the overall conclusions of this review are unchanged from those of the previous review. Foundational evidence for the prior recommendation against screening is based on psychosocial harms associated with false-positive test results due to poor screening test accuracy, especially in populations with low HSV-2 prevalence, and uncertain benefit of preventive viral medications for reducing viral shedding or improving health outcomes.

The Centers for Disease Control and Prevention recommends serologic screening for specific asymptomatic populations at higher risk for infection (eg, persons with HIV or other immunosuppressive conditions).⁵ This current review, however, focused on the general population of asymptomatic adolescents and adults and therefore may not be applicable to populations at higher risk for infection.

Section Editors: Jody W. Zylke, MD, Deputy Editor; Kristin Walter, MD, Senior Editor.

Supplement.

Data Sharing Statement