Marrazzo, Jeanne M. MD, MPH*; Stine, Kathleen NP*; Wald, Anna MD, MPH*†‡
INFECTION WITH HUMAN HERPES simplex virus type-2 (HSV-2) causes the majority of recurrent genital herpes, with a smaller proportion caused by herpes simplex virus type-1 (HSV-1). 1 Recent estimates indicate that the burden of unrecognized HSV-2 disease is substantial. Although 22% of persons 12 years and older in the United States are infected with HSV-2, up to 90% deny having a history of genital herpes. 2,3 As a correlate, most new HSV-2 infections are thought to be acquired from asymptomatic sex partners. 2,4–6 Serologic tests that can distinguish antibody against the glycoprotein-G of HSV-2 from that of HSV-1 offer an accurate estimate of the true prevalence of infection with these viruses. 7
Although the epidemiology of genital herpes has been well described in heterosexuals and in men who have sex with men, 8,9 no study has reported on HSV seroprevalence or acquisition in lesbians. Same-sex behavior among women is not uncommon, with a lifetime incidence estimated at 8% to 20%; 1.4% to 4.3% of all women report current same-sex behavior. 10–12 Sexual acquisition of human immunodeficiency virus (HIV), genital human papillomavirus, trichomoniasis, and syphilis have been reported in women who reported sex only with other women. 13–18 Transmission of HSV requires only contact between mucosal surfaces, or with vulnerable skin, which could be affected by sexual practices among lesbians that include genital–genital and digital–vaginal contact and the use of shared sex toys. 19,20 Furthermore, most lesbians (53–99%) have had sex with men, and many (21–30%) continue to have sex with men. 21,22 Among these women, acquisition of HSV from men can occur, and women infected through this route could serve as a source for subsequent viral transmission to their female partners.
We examined seroprevalence of HSV infection and associated risk factors in a self-referred sample of lesbians.
Beginning in February 1998, women were recruited through advertisements posted in the community (restaurants, bookstores, clubs, bars), newspaper and magazine articles, and referral from community clinicians. Because self-identification as “lesbian” might not predict participation in same-sex behavior or its frequency, we oriented recruitment materials to women who had sex with other women, regardless of self-identification. Women who reported having sex with another woman in the preceding year were eligible. 14 Current symptomatology of STD and prior STD history were not mentioned in recruitment materials. Once enrolled, women were invited to refer their female partners for possible enrollment.
At study entry, a detailed medical and sexual history was obtained using a standardized questionnaire. Pelvic examination was performed. All subjects were interviewed and examined in the same clinic by one clinician (KS). Serum samples were tested for antibodies to HSV-1 and HSV-2 by Western blot (WB) as previously described. 23 Statistical analysis was performed using SPSS software (SPSS, Chicago, IL). Direct comparisons of proportions were made using Pearson chi-squared test or Fisher exact method. Continuous variables were compared between groups using Student t test or the Mann-Whitney test for nonparametric data. Multivariate analysis was performed using logistic regression techniques. Tests of significance were 2-tailed (P <0.05). Couples were defined as “monogamous” if they reported no sex partners outside of their relationship for at least 3 months. The study's procedures were approved annually by the University of Washington Human Subjects Research Review Committee, and all subjects provided written informed consent.
A total of 392 women were recruited, most of whom responded to advertisements in community venues or were referred friends or partners (Table 1). The women were predominantly white, well educated, and less than 30 years old (median age, 28 years). Most women (89%) reported no current genitourinary symptoms; the remainder reported abnormal or increased vaginal discharge or itching. None requested assessment specifically for genital herpes or reported discrete genital lesions. Both members of 71 couples (142 women, 36% of all subjects) were enrolled.
Although most women (66%) self-identified as lesbian, 80% reported having had intercourse with a man during their lifetime, and 28% reported doing so in the previous year. Of 257 women who self-identified as lesbian, 187 (73%) had ever had sex with a man, and 22 (8.6%) had done so in the prior year. Reported median numbers of lifetime male and female sex partners were 7 and 6, respectively. Most subjects (58%) reported only 1 female partner during the prior 6 months. Almost all subjects reported receiving and giving oral–vaginal and digital–vaginal sex with female partners during the last year, and many reported oral-anal or digital–anal sex (34% and 63%, respectively).
Frequency and Correlates of HSV-1 and HSV-2 Infection
Overall, 46% of women were seropositive for HSV-1, and 7.9% were seropositive for HSV-2 (Table 2). In univariate analysis, seropositivity to HSV-1 was associated with older age of subjects, lower income, self-report of oral herpes, higher number of lifetime female partners, and ever having used an insertive sex toy on a female partner. Seropositivity to HSV-2 was associated with older age of subjects, report of prior pregnancy or of douching, self-report of genital herpes, older age at first sex with a female partner, ever having received a cut or piercing during sex with a female partner, a higher number of lifetime male partners, and report of ever having had a male partner with genital herpes. Infection with either HSV type was not associated with self-defined sexual identity, ever having used cocaine, genital symptoms at the time of evaluation, age at first sex with a male partner, or with other sexual behaviors with female partners, including receptive oral–vaginal and receptive and insertive oral–anal, digital–vaginal, and digital–anal sex (data not shown). Figure 1 depicts the relationship between HSV seroprevalence and increasing age, and Figure 2 summarizes the association between HSV seroprevalence and number of reported lifetime male or female sex partners.
The presence of serum antibody to HSV-2 was also significantly associated with reported history of other STD, including trichomoniasis, pelvic inflammatory disease, and gonorrhea (Table 3). Furthermore, a higher number of prior episodes of trichomoniasis was associated with increasing HSV-2 seroprevalence (P = 0.02 for trend; data not shown).
In multivariate analysis (Table 4), increasing age of subjects remained significantly associated with higher seroprevalence of both HSV-1 and HSV-2. However, the associated risk was evident only when subjects were at least 30 years of age and became statistically significant only for subjects 36 years and older. Self-categorization of “other” race was significantly associated with HSV-1 infection. Report of a male sex partner with genital herpes independently predicted seropositivity to HSV-2. In separate models evaluating a recent number of episodes of specific sexual practices and of time since performance of each type of sexual practice, no association with HSV-1 or HSV-2 seropositivity was evident (data not shown).
Knowledge and Accuracy of Self-Diagnosis of HSV Infection
Of the 24 subjects who reported a history of genital herpes (6.1% of all subjects), only 9 (38%) were HSV-2-seropositive and 10 (42%) were HSV-1-seropositive; 5 were seronegative for both HSV-1 and HSV-2. Conversely, only 9 of the 31 subjects (29%) who were seropositive for HSV-2 reported a history of genital herpes. HSV-2 seroprevalence among the 359 subjects who reported no history of genital herpes was 5.8%. Of 80 women who reported a history of oral herpes (20% of all subjects), 59 (69%) were HSV-1-seropositive; however, almost half (40%) of the 300 women who denied oral herpes were HSV-1-seropositive, and only 30% of HSV-1-seropositive women reported a history of oral herpes.
HSV Infection Among Monogamous Sex Partners
Of the 72 couples enrolled in the study, 71 had been monogamous for at least 3 months. Of these, only 1 partner was HSV-1-seropositive in the majority (27 couples; 38%), both partners were HSV-1-seropositive in 25 couples (38%), and neither partner was seropositive in 19 couples (27%). In the majority of couples, both partners were HSV-2-seronegative (60 couples; 85%). One partner was HSV-2-seropositive in 10 couples (14%), and both partners were HSV-2 seropositive in 1 couple (1.4%).
Using a type-specific serologic assay, we found the seroprevalence of HSV-1 and HSV-2 to be 46% and 8%, respectively, among a self-referred group of lesbian and bisexual women. Increasing age independently predicted higher seroprevalence to both HSV-1 and HSV-2, and HSV-2 seropositivity was independently associated with a history of a male sex partner with genital herpes. Of 78 women who reported no prior sex with a male partner, 2 (2.6%) were seropositive for HSV-2. Infection with HSV-2 was also associated with report of prior trichomoniasis, gonorrhea, and pelvic inflammatory disease. As has been demonstrated in other studies, most HSV-2-seropositive subjects (71%) reported no history of genital herpes. 2,4,6 Finally, seroprevalence of HSV-1 increased significantly with an increasing number of female sex partners, suggesting a role for sexual behavior in acquisition of this virus.
The seroprevalence of HSV-2 in our predominantly white subjects is approximately half that reported among 1132 white women in the National Health and Nutrition Examination Survey (NHANES) III study, which tested sera obtained during the years 1988 to 1994 2 and among a similar demographic sample of female blood donors in Germany. 24 Data on the sexual orientation of the women in these studies was not reported, but most were presumably heterosexual. Among 494 heterosexual white women seen at a Seattle primary care clinic in the early 1990s, HSV-2 seroprevalence was 27%; however, subjects in that study were older (median age, 33 years) than our subjects. 4 In the NHANES III population, HSV-2 seroprevalence among white women aged 20 to 29 years old, the subgroup most comparable to our study population, was 18.7% (95% confidence interval, 12.0–18.1). Persons reporting a history of genital herpes, regardless of gender, had an HSV-2 seroprevalence of 81.5%, whereas seroprevalence among those reporting no history of genital herpes was 21.6%. 2 In our subjects, these values were 38% and 6%, respectively. Possible reasons for the lower HSV-2 seroprevalence among our subjects include the potential for less efficient genital transmission of HSV-2 in the absence of penile–vaginal sex; the fact that many of our subjects were part of monogamous partnerships, frequently of long duration; and the predominantly white race of our subjects. In all HSV-2 serosurveys performed to date, blacks have been more likely than other racial or ethnic groups to be infected with HSV-2 and also experienced significantly higher rates of new HSV-2 infections in one prospective study. 6 Furthermore, risk factors for infection with HSV-2 can vary across populations studied. In the NHANES III study, the strongest predictors of HSV-2 infection were race, age, and lifetime number of sex partners (gender not specified), but fewer years of formal education, income below the poverty level, and ever having used cocaine were also independently associated. 2 Of these characteristics, only increasing age independently predicted higher seroprevalence to HSV-2 among our subjects.
Although no previous studies have reported on lesbians’ HSV seroprevalence, other investigators have assessed lesbians’ self-report of genital herpes. Most have used self-referred, volunteer samples and reported a lifetime prevalence of 3.3% to 7.4%. 21,22,25 Our subjects reported a history of genital herpes with a similar frequency (6.1%). However, as noted previously, self-reports of genital herpes substantially underestimated prevalence as measured by type-specific HSV serology. Of related interest is a report describing 27 lesbians seen at an STD clinic in London in the late 1980s; genital herpes was diagnosed by culture in 3 women (11%). 26
Many studies have suggested that the incidence of genital infection with HSV-1 is increasing, 24,27–30 and that new genital HSV-1 infections are as common as oropharyngeal HSV-1 infections. 6 The majority of our subjects (54%) lacked serum antibody to HSV-1. Because genital infection with HSV-1 is most likely acquired during receipt of oral sex, 28 a behavior reported to be commonly practiced by lesbians, 19,20 a substantial proportion of lesbians engaging in receptive oral sex could be at risk for genital acquisition of HSV-1. In fact, our data demonstrated a more prominent association between number of lifetime female sex partners and HSV-1 infection than that reported for male sex partners among the women studied in the NHANES III study. 2 Other investigators have suggested that decreasing HSV-1 seroprevalence among young adults could place these individuals at higher risk for subsequent genital HSV-1 acquisition and have suggested an increased emphasis on education about the risk of orogenital sex. 24,29 Counseling about susceptibility to genital herpes infection could be enhanced by the recent availability of less expensive, type-specific HSV serologic assays that define persons at risk. 31 Our findings also indicate that lesbians could comprise an appropriate target group for immunization with a recently evaluated vaccine against HSV-2, which performed best among women who were seronegative for both HSV-1 and HSV-2. 32
Our study has important limitations. Subjects were self-referred; therefore, they might not be representative of all women who have sex with women or of women who self-identify as lesbian. Most subjects were white, and although median income was relatively high, 31% were uninsured. Our sample size could have also been too small for subgroup analysis to detect statistical significance for several associations found to be significant in univariate analysis such as number of lifetime sex partners. Most subjects reported only 1 female sex partner in the preceding 6 months, and all but 1 of the 72 couples we enrolled had been monogamous for at least 3 months. A study focusing on younger women with higher rates of sex partner change might yield different results.
The prevalence of infection with HSV-1 and HSV-2 among our subjects provides important information that should clarify messages provided to lesbians about their risk of inapparent infection and the potential risk of transmission to sex partners. Our findings support that sexual transmission of HSV-1 occurs between women and suggest that genital HSV-2 transmission can occur, perhaps inefficiently, between female sex partners. Efforts to enhance the recognition of genital herpes among healthcare providers and among all patients, including lesbians, should contribute to control of this common and costly STD.
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