Clinical Context

Genital herpes is a very common and occasionally highly dangerous condition. The authors of the current guidelines, along with an editorial by Hook, provide a review of the epidemiology of genital herpes. The overall prevalence of infection with herpes simplex virus type 2 (HSV-2), the main viral subtype associated with most cases of genital herpes, is 15.3% among US adolescents and adults between 14 and 49 years old. HSV-2 infection is approximately 3 times more common among black individuals compared with whites, and women are twice as likely to harbor infection compared with men. Complicating the epidemiology of genital herpes is that 10% to 20% of new infections are caused by HSV type 1 (HSV-1) only.

The first outbreak of genital herpes is generally the worst, with associated fever and malaise. After a first outbreak, 70% to 90% of patients will have at least 1 more outbreak within 1 year. Asymptomatic patients infected with HSV-2 also have a substantial risk for subsequent symptoms, and 85% of these persons will experience a symptomatic outbreak within 6 months of a positive HSV test result.

Therefore, there is no doubt that genital herpes is common. What other factors are important in forming broad recommendations on screening for HSV and genital herpes, and what did the USPSTF finally recommend in this regard? The answers are detailed in "Recommendation Highlights."

Synopsis and Perspective

Updated recommendations on genital HSV infection screening advise against routine screening in asymptomatic adolescents and adults, including pregnant women. The USPSTF released the final recommendations and an evidence statement on the use of blood tests for screening online December 20, 2016, in JAMA.^[1] They are also available on the USPSTF website.^[2]

The final recommendations are consistent with a draft version made available for public comment in August 2016,^[3] and update the 2005 recommendations.

After thoroughly reviewing the evidence, the USPSTF concluded that the harms associated with screening outweigh the benefits. These recommendations align with those of other major health organizations, including the American Academy of Family Physicians, American College of Obstetricians and Gynecologists (ACOG), and Centers for Disease Control and Prevention (CDC).

"Despite genital herpes being common, testing is not generally helpful for people without symptoms, in part because early identification does not improve a person's health as there is no cure for herpes," said task force member Ann E. Kurth, PhD, MPH, in a USPSTF news release.

"In addition, because current screening methods are often inaccurate, harms of screening include high false-positive rates and potential anxiety and disruption of personal relationships related to diagnosis," she added.

HSV is a sexually transmitted infection (STI) that affects 1 in 6 US individuals 14 to 49 years old. Although antiviral medications can treat the symptoms of HSV infection and prevent outbreaks, they cannot cure the underlying infection. Two types of HSV exist: HSV-1 (mainly oral infection) and HSV-2 (mainly genital infection).

The recommendations also point out that current tests for HSV-1, which is increasingly becoming a genital infection, cannot identify whether the site of infection is oral or genital.

The task force also recommends intensive behavioral counseling for the prevention of STIs in high-risk individuals and advises close observation of recently infected pregnant women. Although neonatal HSV infection is rare, it can be life threatening, and women with active infection at delivery should be offered the option of cesarean delivery.

In a linked editorial,^[4] Edward W. Hook III, MD, from the University of Alabama at Birmingham, supports the recommendations, but with caveats.

"The recommendation against serologic screening for genital HSV is warranted but should concern clinicians and patients and serve as a call to action for the National Institutes of Health, other federal agencies, and industry partners to address this ongoing epidemic, prioritizing development of improved tests and test strategies for diagnosis of HSV," he writes.

He emphasizes genital herpes as a public health problem that is "largely underrecognized." Moreover, HSV infection disproportionately affects non-Hispanic blacks and provides an example of "striking health disparities" in the United States. The strong link between genital herpes and HIV infection provides another reason to tackle the problem.

However, the lack of a national control program, lack of vaccine for prevention, and widespread unawareness of carrier status among infected individuals prove challenging to control efforts. Tests for HSV have not advanced during the last decade, and need improvement. Reducing the stigma and misperceptions about HSV infection is also important to control efforts, according to Dr Hook.

"While it is disappointing that so little progress in test performance has occurred in the more than a decade since the 2005 USPTF recommendation against general population screening for this important and widespread STI, the current USPSTF recommendation should serve to renew efforts to develop better tests for HSV, to improve management strategy, and to address the pervasive and harmful stigma associated with genital herpes," he concludes.

Members of the USPSTF were reimbursed for travel and received an honorarium from the USPSTF, which is an independent voluntary body supported by the Agency for Healthcare Research and Quality. Dr Hook has received grants and/or personal fees from Hologic, Roche Molecular, and Becton Dickinson and research supplies from Cepheid.

JAMA. 2016;316:2493-2494, 2525-2530.

Recommendation Highlights

• The risk for congenital herpes infection of the newborn is a grave concern associated with genital herpes infection. Thankfully, these cases are rare. The estimated prevalence is approximately 10 cases per 100,000 live births.
• Nonetheless, approximately 75% of women with a history of symptomatic genital herpes will have a recurrence during pregnancy, and 14% will have symptoms at the time of delivery.
• 45% of newborns infected with HSV will experience mild symptoms only, but the majority will have an infection of the central nervous system and/or disseminated disease.
• The USPSTF statement describes the limitations of the currently available tests for HSV. HerpeSelect (Focus Diagnostics) is the most commonly used serologic test for HSV-2 infection, and it is associated with a sensitivity of 99% and a specificity of 83%. The biokit HSV-2 Rapid Test (Biokit USA) is a serologic test associated with a sensitivity of 84% and a specificity of 95%.
• The positive predictive values may be as low as 75% for the biokit test and 50% for the HerpeSelect.
• HSV-1 can be detected with serologic testing, but these tests cannot determine the anatomic site of infection.
• Confirmatory testing is not widely applied and is only available in 1 virologic laboratory in the United States.
• The American Academy of Family Physicians, ACOG, and the CDC do not recommend routine screening for HSV infection among asymptomatic individuals. ACOG and the CDC recommend asking about HSV symptoms and offering cesarean delivery for women with prodromal or active symptoms of genital herpes.
• There are potential psychological harms in hearing a false-positive result for HSV infection, although treatment with antiviral therapy is generally well tolerated.
• The USPSTF concludes with moderate certainty that the potential harms associated with screening for genital HSV infection among asymptomatic adolescents and adults outweigh the potential benefits. This is also true for pregnant women. It makes a grade D recommendation against routine screening for genital HSV infection.

Clinical Implications

• An estimated 15% of US individuals are infected with HSV-2, and the majority of infected patients experience symptomatic genital herpes. HSV-2 infections are more common among women and blacks, although up to 20% of new genital herpes cases are caused by HSV-1.
• The USPSTF concludes with moderate certainty that the potential harms associated with screening for genital HSV infection among asymptomatic adolescents and adults outweigh potential benefits. This is also true for pregnant women. It makes a grade D recommendation against routine screening for genital HSV infection.
• Implications for the Healthcare Team: The majority of US adults have not completed all of their health maintenance requirements. The current review and recommendation from the USPSTF should remove screening for genital HSV among asymptomatic individuals from the busy agenda of the healthcare team practicing preventive medicine.

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