• Cynthia Feltner, Catherine Grodensky, Charles Ebel, Jennifer C Middleton, Russell P Harris, Mahima Ashok, and Daniel E Jonas.
• RTI International-University of North Carolina at Chapel Hill Evidence-based Practice Center2Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill3Department of Medicine, University of North Carolina at Chapel Hill.
• JAMA. 2016 Dec 20; 316 (23): 2531-2543.

ImportanceGenital herpes simplex virus (HSV) infection is a prevalent sexually transmitted infection. Vertical transmission of HSV can lead to fetal morbidity and mortality.ObjectiveTo assess the evidence on serologic screening and preventive interventions for genital HSV infection in asymptomatic adults and adolescents to support the US Preventive Services Task Force for an updated recommendation statement.Data SourcesMEDLINE, Cochrane Library, EMBASE, and trial registries through March 31, 2016. Surveillance for new evidence in targeted publications was conducted through October 31, 2016.Study SelectionEnglish-language randomized clinical trials (RCTs) comparing screening with no screening in persons without past or current symptoms of genital herpes; studies evaluating accuracy and harms of serologic screening tests for HSV-2; RCTs assessing preventive interventions in asymptomatic persons seropositive for HSV-2.Data Extraction And SynthesisDual review of abstracts, full-text articles, and study quality; pooled sensitivities and specificities of screening tests using a hierarchical summary receiver operating characteristic curve analysis when at least 3 similar studies were available.Main Outcomes And MeasuresAccuracy of screening tests, benefits of screening, harms of screening, reduction in genital herpes outbreaks.ResultsA total of 17 studies (n = 9736 participants; range, 24-3290) in 19 publications were included. No RCTs compared screening with no screening. Most studies of the accuracy of screening tests were from populations with high HSV-2 prevalence (greater than 40% based on Western blot). Pooled estimates of sensitivity and specificity of the most commonly used test at the manufacturer's cutpoint were 99% (95% CI, 97%-100%) and 81% (95% CI, 68%-90%), respectively (10 studies; n = 6537). At higher cutpoints, pooled estimates were 95% (95% CI, 91%-97%) and 89% (95% CI, 82%-93%), respectively (7 studies; n = 5516). Use of this test at the manufacturer's cutpoint in a population of 100 000 with a prevalence of HSV-2 of 16% (the seroprevalence in US adults with unknown symptom status) would result in 15 840 true-positive results and 15 960 false-positive results (positive predictive value, 50%). Serologic screening for genital herpes was associated with psychosocial harms, including distress and anxiety related to positive test results. Four RCTs compared preventive medications with placebo, 2 in nonpregnant asymptomatic adults who were HSV-2 seropositive and 2 in HSV-2-serodiscordant couples. Results in both populations were heterogeneous and inconsistent.Conclusions And RelevanceSerologic screening for genital herpes is associated with a high rate of false-positive test results and potential psychosocial harms. Evidence from RCTs does not establish whether preventive antiviral medication for asymptomatic HSV-2 infection has benefit.

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