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Increasing Proportion of Herpes Simplex Virus Type 1 as a Cause of Genital Herpes Infection in College Students

Roberts, Craig M. PA-C, MS*; Pfister, John R. MS; Spear, Scott J. MD*

doi: 10.1097/01.OLQ.0000092387.58746.C7

A retrospective review of genital herpes simplex virus (HSV) isolates collected in a university student health service over a 9-year period showed that an increasing proportion of isolates were HSV-1 rather than HSV-2. HSV-1 accounted for 78% of all genital isolates in this population by 2001, compared with 31% of isolates in 1993.

Background Herpes simplex virus (HSV) type 1 is usually thought to cause less than 30% of genital herpes infections in the United States, but the proportion of infections resulting from HSV-1 is increasing in some populations.

Goal The goal was to review the relative proportion of HSV-1 and HSV-2 as the cause of newly diagnosed genital herpes infections in a population of U.S. college students and to assess trends in the change of this proportion over time.

Study Design Genital HSV isolates collected at a university student health service from 1993 to 2001 (n = 499) were reviewed retrospectively. Analyses included comparisons of isolates by HSV type, age group, and sex.

Results The proportion of newly diagnosed genital herpes infections resulting from HSV-1 increased from 31% in 1993 to 78% in 2001 (P <0.001, linear trend P <0.001). HSV-1 was more common in females than males, but increases were noted for both sexes. HSV-1 was more common in persons aged 16 to 21 than in persons aged 22 or older.

Conclusions HSV-1 has become the most common cause of newly diagnosed genital herpes infections in this population of college students and reflects a reversal of the usual HSV-1/HSV-2 ratio.

A retrospective review of genital HSV isolates collected in a university student health service over a nine-year period showed that an increasing proportion of isolates were HSV-1 rather than HSV-2. HSV-1 accounted for 78% of all genital isolates in this population by 2001, compared with 31% of isolates in 1993.

*University Health Services and the Wisconsin State Laboratory of Hygiene, University of Wisconsin-Madison, Madison, Wisconsin

Correspondence: Craig M. Roberts, PA-C, MS, University Health Services, 1552 University Ave., Madison, WI 53726. E-mail:

Received for publication March 11, 2003,

revised May 1, 2003, and accepted May 5, 2003.

GENITAL HERPES IS THE most prevalent sexually transmitted disease (STD) in the United States. 1 Population seroprevalence surveys reveal that herpes simplex virus (HSV) type 2 has infected 22% of U.S. adolescents and adults, 2 and HSV-2 is attributed as the usual cause of genital herpes infection. Although HSV type 1 also causes genital infection, its relative contribution to the overall prevalence of genital herpes infection is less appreciated. In most populations, HSV-1 is thought to cause approximately 30% of genital herpes infections. 3 Sexually acquired genital HSV-1 infection is more common in younger age groups, in women, and in men who have sex with men. 4–6 An increasing proportion of HSV-1 genital isolates has been reported in some populations, particularly in other countries. 6–8

Changes in sexual practices, including oral–genital sexual contact and the use of condoms for vaginal intercourse (which could reduce exposure to genital HSV-2 infection), could contribute to an increasing proportion of HSV-1 versus HSV-2 as a cause of genital herpes infection. 4,8,9 Relatively little data are available to document the frequency of oral–genital sexual behavior among U.S. adults however. In a recent survey of U.S. college students, 75% report having experienced oral–genital sexual contact. 10 It is not unreasonable to expect that a similar proportion of other young adults have had this sexual behavior. In the same survey, 42% of sexually active college students reported they had used a condom “mostly or always” for vaginal intercourse in the previous 30 days, whereas only 3% of respondents reported using condoms for oral sex during the same time period. 10

Although the clinical presentation of genital HSV-1 and HSV-2 infections are similar, their natural history is markedly different. 11 Infections resulting from HSV-1 produce far fewer symptomatic recurrences, 12 and the incidence of viral shedding is much less frequent. 13,14 Persons with genital HSV-1 infection can present a lower risk of transmission to sexual partners and have an improved clinical picture over the long term, potentially changing the prognosis and education messages provided to patients at the time of their original diagnosis.

To determine the relative proportions of HSV-1 and HSV-2 as the cause of newly diagnosed genital herpes infections in a population of college students, we reviewed HSV culture isolate data for genital specimens collected over a 9-year period.

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Isolates used in our analysis were obtained from patients seen in a student health service (SHS) at a large public university in the Midwest (enrollment approximately 40,000 students). The SHS provides STD screening, diagnosis, and treatment to all enrolled students at no charge. The SHS also provides STD services to non-students in the community on a fee-for-service basis. Patient requests for STD screening or symptomatic complaints with an STD concern account for approximately 3600 patient visits each year.

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Laboratory Procedures

Collection of a viral culture for HSV is standard clinical practice within the SHS for any patient presenting with new ulcerative genital lesions. Patients with previously documented genital herpes and recurrent lesions are usually not cultured. A single, established public health reference laboratory was used for all STD testing done in this population, including herpes virus cultures.

Specimens for herpes simplex viral culture were collected on nonreactive cotton or Dacron swabs and the swab placed in viral transport medium. Specimens were maintained at 4°C to 8°C during transport and on receipt in the laboratory, where they were inoculated within 24 to 48 hours onto rhabdomyosarcoma 24-well plate cultures. These were centrifuged at 675 × g for 45 minutes and then incubated at 37°C in the presence of CO2 for 4 days. Cells were examined daily for cytopathic effect (CPE). When CPE was noted, confirmation and identification of viral isolates were performed according to standard immunofluorescence methods using HSV-1- and HSV-2-specific monoclonal antibodies.

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Data Analysis

Specimen and isolation data from all HSV cultures submitted by the SHS to a public health laboratory from January 1, 1993, through December 31, 2001 (n = 675 cultures) were retrieved from the laboratory's electronic database system and provided to the SHS as a computer file. Patient identifiers were removed by the laboratory before the analysis and, as a result, laboratory data could not be linked to other patient clinical data.

The data were analyzed using EpiInfo 2000 software, version 1.1.2 (Centers for Disease Control and Prevention, Atlanta, GA). Isolates were characterized by HSV type and year of collection; patients were characterized by sex and age. A corrected Chi square was used to test for differences in proportions. A Kruskal-Wallis test was used for comparison of mean age. A chi square for trend (Mantel extension) was used to compare proportions over time using each year as a different exposure level.

Only specimens collected from genital sites were included in the analysis. Genital isolates were defined to include those labeled as collected from the following sites: cervix, genital, groin, labia, penis, perineum, pubic, scrotum, urethra, vagina, or vulva. Specimens collected from rectal or buttock sites were not included in the analysis. If multiple or subsequent specimens were submitted from a given patient, only a single isolate was included in the dataset and represents the patient's initial laboratory diagnosis of genital herpes.

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A total of 499 positive HSV isolates were reported during this 9-year period and included in the analysis. Overall, 244 (48.9%) of these isolates were HSV-1 and 362 (72.5%) were in female patients. The proportion of isolates that were HSV-1 increased from 30.9% in 1993 to 77.6% in 2001 (chi square = 24.8; P <0.001) (Table 1). Rate ratios (measured as relative risk) for HSV-1 isolation increased gradually for each successive year compared with the first (P <0.001 by chi square test for trend).



HSV-1 was more common in females than in males (54.1% of isolates versus 35.0%; chi square = 13.7; P <0.001), but increases in the HSV-1 proportion were observed over time for both sexes (Fig. 1). HSV-1 was more common in persons aged 16 to 21 years than in persons age 22 years or older (64.6% of isolates versus 35.9%; chi square = 39.6; P <0.001) and this difference also persisted over time (Fig. 2). Patients with HSV-1 had a lower mean age than patients with HSV-2 (22.0 years versus 24.6 years; Kruskal-Wallis H = 43.9; P <0.001).

Fig. 1

Fig. 1

Fig. 2

Fig. 2

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HSV-1 has become the most common cause of new genital herpes infections in this population of college students and reflects a reversal of the usual HSV-1/HSV-2 ratio. Consistent with other studies, genital herpes resulting from HSV-1 was more common in females and in younger patients. The data reveal a gradual and nearly linear upward trend over time, as HSV-1 became the predominant isolate type in both groups.

Most estimates of the prevalence of genital herpes in the United States have been based on HSV-2 seroprevalence alone. 1,2 The high proportion of genital herpes infections resulting from HSV-1 in this and other populations suggests that the occurrence of genital herpes in the United States could be even greater than previously recognized.

Several factors could explain the high proportion of genital HSV-1 infections in this population. Certainly genital–oral contact with a partner who has oral–labial herpes (which is almost always caused by HSV-1) would explain many of these infections. Although this sexual behavior in college students is common, 10 it is not clear whether oral–genital sex has actually become more frequent or just more frequently discussed. It is also unknown to what extent persons could have oral–genital contact as their only sexual practice with a given sexual partner.

Condom use by college students for vaginal intercourse has increased by as much as 46% between 1985 and 2000. 10,15 The increasing use of condoms for vaginal and anal intercourse in this population could reduce exposures to HSV-2 occurring in sexual partners, resulting in a lower relative incidence of HSV-2 disease. As genital HSV-1 infection becomes more prevalent in a population, one would expect it to account for an increasing proportion of new infections transmitted by unprotected vaginal or anal intercourse. However, this would be offset somewhat by the recognized proclivity of HSV-1 to exhibit less viral shedding from genital tissues and presumably a reduced risk of transmission to partners.

The findings in this study are subject to several limitations. First, this population was not representative of all college students or of all patients with genital herpes. The proportion of genital herpes caused by HSV-1 could be different in other populations and among U.S. college students as a whole. Additionally, the association of virus type with other demographic or clinical variables could not be determined as a result of the absence of identifiers that could be linked to patient records.

These results could have implications for clinical practice as well. Genital HSV-1 infection can generally be expected to have a better prognosis for patients, with fewer recurrences and a milder course. 13 Counseling messages for patients should emphasize the risk of potential exposure to HSV-1 when a sexual partner has a known oral herpes infection. Many patients who successfully implement risk reduction strategies for other STDs could be unaware of this mode of transmission for acquiring genital herpes. Clinicians who use type-specific serology for screening or diagnosis of genital herpes need to consider both the value and limitations of using an HSV-1 serologic test, particularly in young adult populations.

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