An evaluation of the clinical impact of serological testing for herpes simplex virus in a regional UK sexual health service

Abstract

UK guidelines recommend herpes simplex virus (HSV) serology in limited situations, including distinguishing recent from established infections, excluding HSV in recurrent PCR negative lesions, identifying serodiscordant partners, or determining if a pregnant person with known HSV has both types. Challenges with testing include cost, delayed results, and interpretation. We aimed to determine whether HSV serology impacted on patient management. All HSV serology results between 04/10/2021 and 12/12/2025 at our large sexual health service in northwest England were reviewed and matched with HSV PCR results, and demographic and clinical data from patient records. 77 patients had HSV serology of whom 74 (96%) were female and 70 (91%) pregnant. Three (4%) tests were performed to exclude HSV as a cause of recurrent PCR negative ulceration, of which 2 were negative and 1 positive for HSV-1. Twelve (16%) tests were undertaken to identify serodiscordance with partners in pregnancy, with 1 demonstrating serodiscordance. Among pregnant patients, 34 (44%) had testing to identify new infection at first presentation with genital lesions, and 24 (31%) to identify whether both HSV types were present in a patient with known previous infection. Three (4%) patients had serological testing outside of guidelines. Serological testing influenced clinical management for 63 (82%) patients including 1/3 (33%) with recurrent PCR negative lesions, 12/12 (100%) of clinically discordant couples, 27/34 (79%) pregnant patients having serology to differentiate new from established infection on first presentation with lesions, 23/24 (96%) pregnant patients with known genital HSV having serology to determine whether they had antibodies to both HSV types, and 0/3 (0%) patients tested outside of UK guidelines. Despite challenges associated with performing and interpreting HSV serology, clinical management, especially pregnancy decisions, was impacted in the majority of cases. This underscores the necessity for streamlined protocols that facilitate testing as recommended in guidelines.

Keywords

herpes simplex virus serology PCR pregnancy

Introduction

Ano-genital herpes caused by herpes simplex viruses type 1 (HSV-1) or type 2 (HSV-2) is an important sexually transmitted infection with 27,867 diagnoses of first episodes in 2024 in sexual health clinics in England, a 3.5% rise from the year before.¹ Symptoms include painful genital ulceration and may appear years after being infected, or patients may remain asymptomatic but infectious.²

Virus detection and typing are primarily conducted through analysis of PCR swabs from genital lesions during symptomatic episodes.² Although HSV antibody serological testing is available, such testing presents several limitations and therefore is not recommended in the management of anogenital herpes in the majority of cases.² HSV serology may require referral to a specialised laboratory, resulting in delays and diminished clinical utility. Additionally, serology may be both falsely positive or negative, does not confirm site of infection, and positive predictive value in people who have never had genital lesions may be low.^2–4

Therefore, UK guidelines for HSV, and for HSV in pregnancy recommend the use of HSV serology only in limited settings including:

1. To exclude HSV as the cause of the recurrent genital symptoms with persistently negative HSV PCR.

2. To differentiate recent from established infection in people with initial episode genital HSV confirmed by PCR (particularly in pregnancy). In pregnancy, this may support decision making around delivery method, antiviral suppression and management of the neonate.

3. To identify serodiscordant partners (particularly in pregnancy). This may support decision making around transmission risk reduction strategies such as antiviral suppression, condoms, selective abstinence, and disclosure.

4. To identify whether a pregnant person known to have one type of genital HSV has antibodies present to both types. Where patients known to have genital HSV are not known to have both types, advice is for abstinence in the 3rd trimester and, where this has not happened, to consider whether any lesions at delivery could represent an acquisition episode of the second HSV type.^2,4

This study aimed to review whether HSV serology tests at our regional sexual health service in the northwest of England were undertaken in line with UK guidelines, to assess whether HSV serology was concordant with PCR results, and to determine whether undertaking HSV serology had influenced clinical management for patients.

Methods

Laboratory results for all patients having HSV serology between October 4, 2021, and December 12, 2025, were reviewed. Duplicate tests for the same patient were excluded. Serology results were matched with HSV PCR results, and with demographic and clinical data from patient records. Data were extracted into an Excel spreadsheet. Descriptive statistics were used to describe the cohort. Whether serology had influenced clinical management for patients was defined as recommended advice being altered based on results.

Results

HSV serology was performed in 77 patients, of whom 3 (4%) were male, and 74 (96%) were female. There were 70 (91%) pregnant patients. Median age was 28 years (IQR 24–32).

Serology results, clinical outcome and the recommended clinical advice are summarised in Table 1. Serology was undertaken to exclude HSV in 3 (4%) patients with HSV PCR negative recurrent genital lesions, of whom 2 were HSV antibody negative and 1 antibody positive for HSV-1. The HSV-1 positive patient was offered antiviral suppression as they were pregnant, and the site of HSV-1 infection could not be confirmed. One (1%) patient had HSV antibody testing performed on a stored sample taken following sexual assault when they presented months later with genital lesions: PCR and serology were concordant suggesting previous infection unrelated to the assault.

Table 1.

Reasons that patients underwent HSV serology and the clinical outcome.

Reason for serological testing		N (%)	PCR and serology result	Clinical outcome	N (%)	Recommended clinical advice
To exclude HSV as the cause of the recurrent genital symptoms with persistently negative HSV PCR.	Non-pregnant patients	2 (3)	PCR and serology negative	No evidence of HSV	2 (3)
	Pregnant patient	1 (1)	PCR negative, serology positive for HSV-1	Previous HSV-1 infection but cannot confirm site of infection.	1 (1)	Vaginal delivery can proceed. Abstinence in 3rd trimester, if no abstinence and lesions at delivery may be acquisition of other type requiring section. Antiviral suppression in pregnancy.
	Pregnant patient	1 (1)	PCR negative, serology positive for HSV-1	Remains at risk of acquisition of 2nd type of HSV	1 (1)
To differentiate recent from established infection at first presentation	3rd trimester of pregnancy	20 (26)	PCR and serology concordant HSV types	Recurrence of previous infection but remains at risk of acquisition of 2nd type of HSV	7 (9)
			PCR negative, serology positive for HSV-1 or -2	Previous infection without evidence of current lesions, but remains at risk of acquisition of 2nd type of HSV	3 (4)
			PCR and serology concordant HSV types, both HSV types serology positive	Previous infection confirmed, no risk of acquisition of 2^nd HSV type	4 (5)	Vaginal delivery can proceed. Antiviral suppression in pregnancy.
			PCR and serology discordant HSV types	New infection with other HSV type confirmed	1 (1)	Caesarean section advised.
			Serology result not available until post delivery	Unable to modify management so presume new infection	2 (3)	Caesarean section advised.
			Negative PCR, negative serology	No evidence of HSV	3 (4)
	1st and 2nd trimester of pregnancy	14 (18)	PCR and serology concordant HSV types	Recurrence of previous infection but remains at risk of acquisition of 2nd type of HSV	5 (7)	Abstinence in 3rd trimester, if no abstinence and lesions at delivery may be acquisition of other type requiring section. Antiviral suppression in pregnancy.
			PCR positive, serology negative	New infection in early pregnancy, remains at risk of acquisition of 2nd HSV type	2 (3)
			PCR negative, serology positive for HSV-1 or -2	Previous infection without evidence of current lesions but remains at risk of acquisition of 2nd type of HSV	1 (1)
			PCR and serology concordant HSV types, both HSV types serology positive	Previous infection confirmed, no risk of acquisition of 2nd type	4 (5)	Antiviral suppression in pregnancy.
			PCR negative, serology negative	No evidence of HSV	2 (3)
	Lesions after sexual assault	1 (1)	PCR and serology concordant HSV types	Previous infection confirmed	1 (1)
To identify serodiscordant partners in clinically discordant couples	Pregnant patients	10 (13)	Serology demonstrates couple serodiscordance	No evidence of previous HSV infection, at risk of acquisition in pregnancy	1 (1)	Abstinence in 3rd trimester, lesions at delivery may be new acquisition of HSV requiring caesarean section. Antiviral suppression offered to HSV-positive partner.
	Pregnant patients	10 (13)	Partner serology concordant	Previous HSV infection confirmed in both partners	9 (12)	Vaginal delivery can proceed. Antiviral suppression in pregnancy. For those without positive serology to both HSV types, abstinence in the third trimester recommended.
	Partners of pregnant people	2 (3)	Partner serology concordant	Previous HSV infection confirmed in both partners	2 (3)
To identify whether a pregnant person with known HSV has antibodies present to both HSV types		24 (31)	Serology positive for both HSV types	Previous infection with both HSV types	7 (9)	Vaginal delivery can proceed. Antiviral suppression in pregnancy.
			Serology positive for one HSV type	Previous infection with one HSV type and at risk of acquisition of 2nd HSV type	16 (21)	Abstinence in 3rd trimester, if no abstinence and lesions at delivery may be acquisition of other type requiring section. Antiviral suppression in pregnancy.
			Serology result not available until post delivery	Unable to modify management	1 (1)
Patients tested outside the guidelines	Patient with known HSV-2 who was trying to conceive	1 (1)	Serology positive for HSV-2	Previous HSV infection at risk of acquisition of 2^nd type before or during any future pregnancy	1 (1)	Requires retesting in pregnancy as could acquire other type of HSV and develop immunity before then.
	First presentation genital lesion	1 (1)	PCR negative, serology negative	No evidence of HSV	1 (1)
	Pregnant patient already known to have both HSV-1 and HSV-2	1 (1)	Serology positive for both HSV types	Previous infection with both HSV types	1 (1)	Vaginal delivery can proceed. Antiviral suppression in pregnancy.

Twelve (16%) patients had serology undertaken to attempt to identify serodiscordance with sexual partners in pregnancy, of these 10 were pregnant and 2 were partners of pregnant people. In 11 patients, serology confirmed a seroconcordant relationship and no transmission risk reduction counselling was required, but antiviral suppression was offered in pregnancy, and (for those without positive serology to both HSV types) abstinence in the third trimester recommended. One patient had negative HSV serology indicating a serodiscordant relationship and risk reduction counselling was undertaken.

Thirty-four (44%) pregnant patients had testing to identify new infection at first presentation with genital lesions, and 24 (31%) to identify whether both HSV types were present in a patient with known previous infection.

Three (4%) patients had serological testing outside of UK guidelines: 1 attempting to conceive with known HSV-2 (serology positive for HSV-2), 1 with a first presentation of a genital lesion (serology and PCR negative), and 1 who was pregnant and previously diagnosed with PCR-demonstrated HSV-1 and HSV-2 (serology positive for HSV-1 and -2). Management was not altered by serology in these cases.

There were 59 (77%) symptomatic patients who had simultaneous HSV PCR testing with serology. Of these, 46 (78%) showed PCR concordance with serology, 10 (17%) had positive serology despite negative PCR, and 3 (5%) had positive PCR with negative serology, suggesting primary HSV infection.

Serological testing influenced clinical management for 63 (82%) patients including in 1/3 (33%) with recurrent PCR negative lesions, 12/12 (100%) clinically discordant couples, 27/34 (79%) pregnant patients having serology to differentiate new from established infection on first presentation with genital lesions, 23/24 (96%) pregnant patients with known genital HSV having serology to determine whether they had antibodies to both HSV types, and 0/3 (0%) patients tested outside of UK guidelines.

Discussion

Serology informed management in the vast majority of pregnant patients, including 11 (14%) who would have otherwise been advised to have a caesarean section due to uncertainty about new HSV acquisition in the third trimester. In 3 (4%) cases, late presentation meant serology results were unavailable before delivery. In such situations, a cautious approach to clinical decisions must be adopted on the presumption that the patient is presenting with first episode infection.⁴ This highlights the limitation posed by delays in receiving serology results from laboratories, reducing the practical utility of HSV serology in time-sensitive scenarios. Establishing pathways with local and regional laboratories to support rapid testing will limit delays and should be implemented by all services.

Serology demonstrated very little serodiscordance in clinically discordant couples. Transmission often occurs early in relationships due to asymptomatic shedding and may remain clinically inapparent to the newly infected partner.² However, identifying serodiscordant partners through serology aids in perinatal counselling, especially around the topic of abstinence in the final stages of pregnancy and other methods of transmission risk reduction including aciclovir suppression for the HSV positive partner of the pregnant person.⁴

Numbers are small, but serology did not usefully impact care in most patients with recurrent HSV PCR negative genital lesions, or those tested outside of national guidance. Guidelines are based on best available evidence and expert opinion and, although there may be clinically sensible reasons to deviate from guidelines, careful consideration to the clinical utility of doing so should always be considered.

In some cases where there was discordance between PCR and serology results, the clinical suspicion of genital herpes was low but despite this, HSV serology was taken at the same time as PCR swabs for convenience, particularly in pregnancy where time may be limited. Given no evidence of clinical herpes in these patients, they were ultimately receiving HSV serology as a screening test, a strategy not recommended in UK screening guidelines in pregnancy.⁵ When positive HSV serology was incidentally identified in some, patients were advised to consider aciclovir suppression from 32 weeks of pregnancy.⁴

It became apparent during case note review that there is suboptimal public awareness of the implications of patient or partner HSV infections in pregnancy as patients with known HSV were presenting later in pregnancy for outbreak treatment, rather than knowing to present earlier in pregnancy to discuss antiviral suppression. Education of pregnant people and antenatal staff is essential to ensure appropriate serology testing, antiviral suppression and delivery decision making for all those who would benefit.

In one case, a patient developed genital HSV weeks after an assault. HSV serology was tested on a sample taken at the time of assault to differentiate new from existing infection; a negative result could help link acquisition to the assault and guide suspect testing.⁶ In this case, serology was positive, indicating a pre-existing infection, so management was unchanged.

Our study is limited by small sample size, despite consisting of 4 years of data from a regional service. Recent changes in national pregnancy guidelines in 2024 may have affected testing patterns during the study period, potentially leading to underrepresentation of certain patient groups who would now be eligible for testing.⁴ However, our small sample size also suggests that HSV serology is unlikely to be a significant financial burden for services and should therefore be offered in line with UK guidance without financial restriction.^2,4

Although there are challenges in both performing and interpreting HSV serology, our data suggest that clinical management, and particularly pregnancy-related decision-making, is impacted in the majority of cases. Sexual health services should ensure a streamlined pathway with laboratory partners is developed to enable serology to be undertaken in line with UK guidelines, optimising outcomes for patients.^2,4

Footnotes

ORCID iDs

Catriona Boyd

Emily Clarke

Ethical considerations

Ethical approval not required. This audit was approved by the Trust Audit Department.

Consent to participate

Not required. This audit was approved by the Trust Audit Department.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Emily Clarke is Chair of the British Association for Sexual Health and HIV (BASHH) Herpes Simplex Virus Special Interest Group, and has been PI of GSK funded trials of vaccination for HSV. Dr Martyn Wood and Dr Catriona Boyd declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

Available on reasonable request to corresponding author.*

References

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