Herpes simplex virus-2 as a human papillomavirus cofactor in the etiology of invasive cervical cancer.

BACKGROUND: Human papillomavirus (HPV) infection is the main cause of invasive cervical cancer, but cofactors may act in conjunction with HPV. We performed a pooled analysis of seven case-control studies to examine the effect of one possible HPV cofactor, herpes simplex virus-2 (HSV-2) infection, in the etiology of invasive cervical cancer. METHODS: Blood and exfoliated cervical specimens were obtained from 1263 case patients with invasive cervical cancer (1158 with squamous-cell carcinomas and 105 with adeno- or adenosquamous-cell carcinomas) and 1117 age-matched control subjects. Western blot analysis and/or an enzyme-linked immunosorbent assay were used to detect type-specific serum antibodies to HSV-2 and HSV-1, and Chlamydia trachomatis serum antibodies were detected using a micro-immunofluorescence assay. HPV DNA was detected using a polymerase chain reaction assay. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were computed from unconditional logistic regression models. RESULTS: Overall, HSV-2 seropositivity was higher among case patients with squamous-cell carcinoma (44.4%, 95% CI = 41.5% to 47.3%) or adeno- or adenosquamous-cell carcinoma (43.8%, 95% CI = 34.2% to 53.5%) than among control subjects (25.6%, 95% CI = 23.0% to 28.2%). Cervical specimens from 1098 (94.8%) squamous-cell carcinoma case patients, 95 (90.5%) adeno- or adenosquamous carcinoma case patients, and 164 (14.7%) control subjects were positive for HPV DNA. Among the HPV DNA-positive women, HSV-2 seropositivity was associated with increased risks of squamous-cell carcinoma (OR = 2.19, 95% CI = 1.41 to 3.40) and adeno- or adenosquamous-cell carcinoma (OR = 3.37, 95% CI = 1.47 to 7.74) after adjustment for potential confounders. A similar association between HSV-2 seropositivity and squamous-cell carcinoma risk was observed after further controlling for markers of sexual behavior (OR = 1.96, 95% CI = 1.24 to 3.09). Among control subjects, HSV-2 seropositivity was associated with markers of sexual behavior, but not with cervical HPV DNA positivity. CONCLUSION: HSV-2 infection may act in conjunction with HPV infection to increase the risk of invasive cervical carcinoma.

Correlates of human herpesvirus 8 seropositivity among heterosexual men in Kenya.

BACKGROUND: Several studies have suggested that sexual transmission of human herpesvirus 8 (HHV-8) occurs among homosexual men in developed countries. However, few studies have examined heterosexual HHV-8 transmission, especially among African populations in which HHV-8 is endemic. OBJECTIVES: To determine the seroprevalence and correlates of HHV-8 infection among heterosexual African men. DESIGN: Cross-sectional study. METHODS: Participants were 1061 men enrolled in a prospective cohort study of risk factors for HIV-1 acquisition among trucking company employees in Mombasa, Kenya. Stored frozen sera from the study baseline visit were tested for antibodies to HHV-8 by whole-virus lysate ELISA. RESULTS: HHV-8 seroprevalence was 43%. In multivariate logistic regression analysis, HHV-8 infection was independently associated with older age [for men aged 30-39 years: odds ratio (OR), 1.5; 95% confidence interval (CI), 1.1-2.0; for men aged > or = 40 years: OR, 1.7; 95% CI, 1.1-2.7, compared with men aged < 30 years], Christian religion (OR, 1.6; 95% CI, 1.2-2.1), being uncircumcised (OR, 1.5; 95% CI, 1.0-2.2), and ever having syphilis (OR, 2.2; 95% CI, 1.4-3.5). Ever having used condoms was associated with decreased likelihood of infection (OR, 0.7; 95% CI, 0.6-1.0). Seropositivity was not significantly related to other sexual behaviors characterized or to HIV-1 status. CONCLUSIONS: HHV-8 seropositivity is common in this population and increases with age, suggesting on-going transmission during adulthood. Infection was more common among men who were uncircumcised or who had ever had syphilis and was less common among those who had ever used condoms, suggesting that sexual factors may play a role in HHV-8 transmission. Prospective studies of HHV-8 acquisition in heterosexual African populations are needed to demonstrate whether safer sexual practices can reduce transmission.

Association between cervical shedding of herpes simplex virus and HIV-1.

OBJECTIVE: To investigate the association between the cervical shedding of herpes simplex virus (HSV) and HIV-1. DESIGN: A cross-sectional study on 200 women seropositive for both HSV-2 and HIV-1 was conducted in a family planning clinic at the Coast Provincial General Hospital, Mombasa, Kenya. MAIN OUTCOME MEASURES: Quantities of HSV DNA (types 1 and 2) and HIV-1 RNA as well as the presence or absence of HIV-1 proviral DNA in cervical secretions were determined and compared. RESULTS: There was a significant correlation between the quantities of HSV DNA and HIV-1 RNA in the cervical secretions of HSV-shedding women (Pearson's r = 0.24, P = 0.05). A 10-fold increase in the quantity of cervical HSV DNA was associated with 1.35-fold higher cervical HIV-1-RNA levels (95% CI 1.00-1.81; P = 0.05), and with 1.36-fold greater odds of detection of HIV-1 proviral DNA (95% CI 1.05-1.75; P = 0.02). CONCLUSION: Higher levels of cervical HSV were associated with higher levels of expressed HIV-1 and with the more frequent detection of HIV-1-infected cells in cervical secretions. Prospective studies are needed to explore further the association between non-ulcerative cervical HSV reactivation and HIV-1 shedding. Such a relationship may have important implications for interventions designed to slow the spread of HIV-1.

Markers of viral infection in monozygotic twins discordant for chronic fatigue syndrome.

To estimate the prevalence of viruses associated with chronic fatigue syndrome (CFS) and to control for genetic and environmental factors, we conducted a co-twin control study of 22 monozygotic twin pairs, of which one twin met criteria for CFS and the other twin was healthy. Levels of antibodies to human herpesvirus (HHV)-8, cytomegalovirus, herpes simplex virus 1 and 2, and hepatitis C virus were measured. Polymerase chain reaction (PCR) assays for viral DNA were performed on peripheral blood mononuclear cell specimens to detect infection with HHV-6, HHV-7, HHV-8, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, varicella zoster virus, JC virus, BK virus, and parvovirus B19. To detect lytic infection, plasma was tested by PCR for HHV-6, HHV-8, cytomegalovirus, and Epstein-Barr virus DNA, and saliva was examined for HHV-8 DNA. For all assays, results did not differ between the group of twins with CFS and the healthy twins.

A systematic study of Epstein-Barr virus serologic assays following acute infection.

We determined the presence of IgG and IgM antibody to viral capsid antigen (VCA-IgG, VCA-IgM) and IgG antibody to the Epstein-Barr virus nuclear antigen (EBNA) by indirect immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA) during the acute illness and at 1, 2, 6, and 48 months in a prospective population-based case series of 95 persons with an acute illness serologically confirmed as Epstein-Barr virus infection. The acute illness was characterized by the presence of VCA-IgG and VCA-IgM (by ELISA) and by the absence of EBNA in most, but not all, patients. During follow-up, VCA-IgG antibodies remained detectable in all patients, while the proportion with VCA-IgM declined and the number with detectable EBNA antibodies steadily increased. The primary differences between the 2 serologic test methods were the increased persistence of VCA-IgM during follow-up by ELISA and the earlier detection of EBNA by IFA. Clinicians should consider the illness stage and the laboratory technique to appropriately interpret serologic test results in suspected cases of mononucleosis caused by the Epstein-Barr virus.

HSV-2 serology can be predictive of HIV epidemic potential and hidden sexual risk behavior in the Middle East and North Africa.

BACKGROUND: HIV prevalence is low in the Middle East and North Africa (MENA) region, though the risk or potential for further spread in the future is not well understood. Behavioral surveys are limited in this region and when available have serious limitations in assessing the risk of HIV acquisition. We demonstrate the potential use of herpes simplex virus-2 (HSV-2) seroprevalence as a marker for HIV risk within MENA. METHODS: We designed a mathematical model to assess whether HSV-2 prevalence can be predictive of future HIV spread. We also conducted a systematic literature review of HSV-2 seroprevalence studies within MENA. RESULTS: We found that HSV-2 prevalence data are rather limited in this region. Prevalence is typically low among the general population but high in established core groups prone to sexually transmitted infections such as men who have sex with men and female sex workers. Our model predicts that if HSV-2 prevalence is low and stable, then the risk of future HIV epidemics is low. However, expanding or high HSV-2 prevalence (greater than about 20%), implies a risk for a considerable HIV epidemic. Based on available HSV-2 prevalence data, it is not likely that the general population in MENA is experiencing or will experience such a considerable HIV epidemic. Nevertheless, the risk for concentrated HIV epidemics among several high-risk core groups is present. CONCLUSIONS: HSV-2 prevalence surveys provide a useful mechanism for identifying and corroborating populations at risk for HIV within MENA. HSV-2 serology offers an effective tool for probing hidden sexual risk behaviors in a region where quality behavioral data are limited.

Worldwide human papillomavirus etiology of cervical adenocarcinoma and its cofactors: implications for screening and prevention.

BACKGROUND: Most cancers of the uterine cervix are squamous cell carcinomas. Although the incidence of such carcinomas of the uterine cervix has declined over time, that of cervical adenocarcinoma has risen in recent years. The extent to which human papillomavirus (HPV) infection and cofactors may explain this differential trend is unclear. METHODS: We pooled data from eight case-control studies of cervical cancer that were conducted on three continents. A total of 167 case patients with invasive cervical adenocarcinoma (112 with adenocarcinoma and 55 with adenosquamous carcinoma) and 1881 hospital-based control subjects were included. HPV DNA was analyzed in cervical specimens with the GP5+/6+ general primer system followed by type-specific hybridization for 33 HPV genotypes. Blood samples were analyzed for chlamydial and herpes simplex virus 2 (HSV-2) serology. Multivariable unconditional logistic regression modeling was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs). All tests of statistical significance were two-sided. RESULTS: The adjusted overall odds ratio for cervical adenocarcinoma in HPV-positive women compared with HPV-negative women was 81.3 (95% CI = 42.0 to 157.1). HPV 16 and HPV 18 were the two most commonly detected HPV types in case patients and control subjects. These two types were present in 82% of the patients. Cofactors that showed clear statistically significant positive associations with cervical adenocarcinoma overall and among HPV-positive women included never schooling, poor hygiene, sexual behavior-related variables, long-term use of hormonal contraception, high parity, and HSV-2 seropositivity. Parity had a weaker association with adenocarcinoma and only among HPV-positive women. Use of an intrauterine device (IUD) had a statistically significant inverse association with risk of adenocarcinoma (for ever use of an IUD compared with never use, OR = .41 [95% CI = 0.18 to 0.93]). Smoking and chlamydial seropositivity were not associated with disease. CONCLUSIONS: HPV appears to be the key risk factor for cervical adenocarcinoma. HPV testing in primary screening using current mixtures of HPV types and HPV vaccination against main HPV types should reduce the incidence of this cancer worldwide.

Performance and use of HSV type-specific serology test kits.

Herpes simplex virus type-specific serology tests based on glycoprotein gG-1 and/or gG-2 are important diagnostic tools to establish aetiology of genital symptoms and identify patients with unrecognized genital herpes. Clinicians can now select from three very different Food and Drug Administration-licensed kits. Diagnology's POCkittrade mark HSV-2 is a point of care test for herpes simplex virus type 2 (HSV-2) antibodies. Clinicians can perform this test while the patient waits. Focus Technologies' HerpeSelect enzymelinked immunosorbent assays (ELISAs) for herpes simplex virus type 1 (HSV-1) and HSV-2 are more traditional tests that can be semiautomated for high throughput at low cost in laboratories. Focus Technologies' HerpeSelect Immunoblot is a novel strip immunoblot that can be used for low volume testing in laboratories or even by healthcare facilities that are accredited for moderately complex testing. This review summarizes the performance data of these tests and describes how to interpret their results. Finally, situations that warrant follow-up testing are described along with suggested strategies for such testing.

Prevention of herpes simplex virus type 2 transmission with antiviral therapy.

Worldwide, herpes simplex virus type 2 (HSV-2) infection is the biggest cause of genital ulcer disease, and is responsible for the majority of cases of genital herpes. The risk of transmitting genital herpes to a partner is one of the leading causes of psychological distress for those with the disease. Antiviral compounds available for the treatment of genital herpes are known to reduce clinical recurrence rates and HSV shedding. This understanding provided impetus for a randomized, placebo-controlled study to assess the ability to interrupt transmission of HSV using oral valaciclovir therapy (500 mg, once daily). The study enrolled 1484 immunocompetent, heterosexual, monogamous couples in stable relationships where both partners were aware of the source partner's infection and the source partner had symptomatic genital herpes. Valaciclovir reduced the risk of transmitting HSV-2 infection by 48%. Furthermore, valaciclovir reduced the risk of clinical disease in the susceptible partner by 75%. As a result, the International Herpes Management Forum (IHMF) now recommends that physicians offer suppressive valaciclovir therapy to immunocompetent individuals concerned about transmitting genital herpes to a heterosexual partner, and advises safer sex behaviour, including the use of condoms, to prevent genital herpes transmission.

Genital shedding of herpes simplex virus among men.

Epidemiologic studies suggest that most sexual transmission of genital herpes occurs when persons shed virus but lack lesions. This study assessed 79 men (63 with a history of genital herpes simplex virus [HSV] type 2 infection, 5 with a history of genital HSV-1 infection, and 11 with HSV-2 antibodies but no history of genital herpes) and obtained daily swabs for viral culture. HSV was isolated at least once from 60 (81%) HSV-2-seropositive men. The total viral shedding rate in HSV-2-seropositive men was 5%; the subclinical shedding rate was 2.2%. Of 11 HSV-2-seropositive men without a genital herpes history, 7 recognized typical recurrences and HSV was detected in 10. The shedding rate among men with genital HSV-2 was significantly higher than among men with genital HSV-1 infection (odds ratio, 4.4; 95% confidence interval, 1.2-15.3). The frequency of viral shedding in men with genital herpes appears comparable with that in women.

Detection of herpes simplex virus type 2-specific immunoglobulin G antibodies in African sera by using recombinant gG2, Western blotting, and gG2 inhibition.

Sera (n = 781) from four African countries were used to determine the prevalence of herpes simplex virus type 2 (HSV-2) antibodies by using the HerpeSelect HSV-2 enzyme-linked immunosorbent assay (ELISA; Focus Technologies) and Western blotting (WB). Also, an HSV inhibition assay was developed to evaluate the discordant sample results between HerpesSelect and WB. The seroprevalence of HSV-2 ranged from 17% in the South African panel to nearly 70% in panels from Kenya, Uganda, and Zimbabwe. Overall, HerpeSelect was 100% sensitive and 88% specific compared to WB and 100% sensitive and 96% specific compared to the inhibition assay. There was 100% concordance among all three assays for samples from South Africa and Zimbabwe. The discordant results occurred in samples from Kenya and Uganda.

Performance of two commercial glycoprotein G-based enzyme immunoassays for detecting antibodies to herpes simplex viruses 1 and 2 in children and young adolescents.

In 61 patients 1 to 14 years of age, the Gull/Meridian enzyme-linked immunosorbent assay (ELISA) had a sensitivity of 100% for herpes simplex virus type 1 (HSV-1) and specificities of 74% for HSV-1 and 48% for HSV-2. In 128 similarly aged patients, the HerpeSelect ELISA (Focus Technologies) showed sensitivities of 80% for HSV-1 and 88% for HSV-2, and specificities of 97% for HSV-1 and 100% for HSV-2.

Longitudinal reliability of focus glycoprotein G-based type-specific enzyme immunoassays for detection of herpes simplex virus types 1 and 2 in women.

Serologic assays that utilize herpes simplex virus (HSV) type-specific glycoproteins G-1 (HSV-1) and G-2 (HSV-2) to discriminate between antibodies against HSV-1 and HSV-2 are sensitive and specific. However, the high rates of seroreversion, defined as the change in an individual's antibody status from positive to negative over time, previously reported in longitudinal evaluations of glycoprotein G type-specific tests suggests that their use in HSV acquisitional studies would be problematic. To further explore the reliability of the glycoprotein G-based serologic tests, we evaluated HSV-1 and HSV-2 enzyme immunoassays from Focus Technologies in a longitudinal cohort of 1207 young women from Pittsburgh, Pa. On enrollment of the women in the study, HSV-1 and HSV-2 antibodies were detected in 46.6 and 24.9% of the women, respectively. Among the women with at least three visits, 3.4% (15 of 447) of those who were HSV-1 antibody positive had a subsequent negative result while fewer than 1% (2 of 227) of those who were HSV-2 antibody positive seroreverted. The median of mean positive index values for women who seroreverted to HSV-1 antibody was lower than that for women who remained seropositive (1.25 versus 7.06; P < 0.001). Similarly, the median of mean positive index values for women whose HSV-2 antibody status reverted from positive to negative was lower than that for those women who did not serorevert (1.83 versus 7.46; P = 0.02). Comparative Western blot analysis demonstrated that the lower positive index values, seen more often among the HSV seroreverters, often signified false-positive immunoassay results. Overall, the seroreversion rates were low; the use of glycoprotein G-based serologic tests for the measurement of HSV-1 and HSV-2 antibodies in incidence studies therefore appears warranted.

Assessment of a combined testing strategy for detection of antibodies to human herpesvirus 8 (HHV-8) in persons with Kaposi's sarcoma, persons with asymptomatic HHV-8 infection, and persons at low risk for HHV-8 infection.

The performance of a human herpesvirus 8 (HHV-8) enzyme immunoassay (EIA) and selective subsequent use of an HHV-8 immunofluorescence assay (IFA) was tested in persons unlikely to be infected with HHV-8 and those who had HHV-8 detected in their saliva. The IFA was performed on samples within a range of EIA optical densities (0.15 to 0.35) where there was considerable overlap between HHV-8-infected and uninfected individuals. The sensitivity of the testing strategy was 88%, with a specificity of 97%.

T cell immunity to herpes simplex viruses in seronegative subjects: silent infection or acquired immunity?

During the course of investigating T cell responses to HSV among volunteers entering trials of investigational genital herpes vaccines, 6 of the 24 immunocompetent subjects with no prior history of oral/labial or genital herpes possessed HSV-specific T cell immunity but, by multiple determinants of even the most sensitive serological assays, remained seronegative to HSV-1 and -2. Of these six immune seronegative (IS; HSV-seronegative with HSV-specific T cell responses) subjects, two had transient HSV-specific T cell responses, while four had CD4(+) and CD8(+) T cell responses directed at HSV that persisted for up to 4 years. CD4(+) T cell clones were isolated that recognized and had high binding affinities to epitopes in HSV-2 tegument proteins. All six IS subjects had potential sexual exposure to an HSV-2-infected sexual partner. Oral and genital mucosal secretions were sampled and tested for the presence of infectious HSV and HSV DNA. No evidence of HSV was detected in >1500 samples obtained from these IS subjects. The identification of persistent T cell responses to HSV in seronegative subjects is a novel finding in the herpesvirus field and suggests either undetected infection or acquired immunity in the absence of infection. Understanding the basis of these acquired immune responses may be critical in developing effective vaccines for genital herpes.

Epidemic Lymphogranuloma venereum during epidemics of crack cocaine use and HIV infection in the Bahamas.

BACKGROUND: Since the early 1980s, the Bahamas has experienced sequential epidemics of freebase/crack cocaine use, genital ulcer-inguinal adenopathy disease (GUD), and heterosexual HIV infection. GOAL: To prospectively define the etiology of GUD in patients at the Princess Margaret Hospital during outbreaks of crack cocaine use, GUD, and HIV infection in the Bahamas. STUDY DESIGN: In Nassau, 47 consecutive patients with GUD underwent serologic testing for syphilis and for infections with HIV, herpes simplex virus type 2 (HSV-2), and Chlamydia trachomatis. Genital ulcer specimens were tested by culture and/or polymerase chain reaction (PCR) assay for Haemophilus ducreyi; by PCR and/or antigen assay for HSV; and by PCR for C trachomatis. Lymph node aspirates were tested by PCR for C trachomatis and H ducreyi. RESULTS: Twenty patients (43%) had HIV infection; eight had lymphogranuloma venereum (LGV), confirmed by PCR detection of C trachomatis sequences consistent with the L2 serovar; and nine others had possible LGV, on the basis of serum microimmunofluorescent C trachomatis antibody titers > or =256. Inguinal lymphadenopathy or bubo was present in 15 of 17 patients, who thus met the laboratory criteria for definite or possible LGV, and in 7 of 30 who did not meet such laboratory criteria (P < 0.001). Thirteen patients had confirmed genital herpes, seven had confirmed chancroid, and four had probable or possible primary syphilis. CONCLUSIONS: The epidemics in the Bahamas of crack use, heterosexual HIV infection, and GUD apparently included epidemic transmission of LGV.

A prospective study of hormonal contraceptive use and cervical shedding of herpes simplex virus in human immunodeficiency virus type 1-seropositive women.

Cross-sectional analyses have demonstrated an association between use of hormonal contraceptives and shedding of herpes simplex virus (HSV). This prospective study evaluated the effect of initiating use of hormonal contraception on cervical HSV detection. Two hundred women who were seropositive for HSV-2 and human immunodeficiency virus (HIV) type 1 were examined for cervical mucosal HSV by use of quantitative DNA polymerase chain reaction before and after beginning the use of hormonal contraceptives. Cervical HSV was detected in 32 women (16.0%) before initiating and in 25 women (12.5%) after initiating use of hormonal contraception (P=.4). There were no significant differences in HSV shedding among the subgroups of women starting combination oral contraceptives containing both estrogen and progesterone or progesterone-only contraceptives. Among the 54 women who shed HSV at least once, the median change in cervical HSV after initiation of hormonal contraception was -313 copies/swab. In this prospective study, use of hormonal contraceptives did not increase detection of cervical HSV.

Human herpesvirus 8: seroprevalence and correlates in prostitutes in Mombasa, Kenya.

Human herpesvirus 8 (HHV-8) infection is very prevalent in sub-Saharan Africa, but the role of sexual transmission has not been well characterized. HHV-8 seroprevalence and correlates were evaluated in a cohort of female prostitutes in Mombasa, Kenya. Between February 1993 and January 2000, stored plasma samples taken from 736 women were tested, by whole-virus ELISA assay, for the presence of HHV-8 antibodies; of these 736 women, 633 were included in the analysis of correlates of HHV-8 infection; and, of these 633, 44.1% were seropositive for HHV-8 antibodies. In univariate analysis, age, years of education, years of prostitution, workplace, hormonal contraception, intrauterine-device use, alcohol consumption, syphilis, and gonorrhea were all significantly associated with the presence of HHV-8 antibodies. In a multivariate model, older age, fewer years of education, and 2 markers of high-risk sexual behavior-namely, alcohol consumption and gonorrhea-were each independently associated with HHV-8 seropositivity. These results suggest that heterosexual transmission may contribute to acquisition of HHV-8 infections in this African population of prostitutes.

The etiology and management of genital ulcers in the Dominican Republic and Peru.

BACKGROUND: Clinical diagnosis of genital ulcers is difficult, and diagnostic tests are least available in settings where rates of disease are highest. The World Health Organization (WHO) has developed protocols for the syndromic management of genital ulcers in resource-poor settings. However, because risk factors, patterns and causes of disease, and antimicrobial susceptibilities differ from region to region and over time, they must be adapted to local situations. GOAL: The goal of this study was to determine etiologic factors, evaluate syndromic management, and compare polymerase chain reaction (PCR) testing with other diagnostic alternatives for genital ulcers among patients attending sexually transmitted disease clinics in the Dominican Republic and Peru. STUDY DESIGN: Eighty-one men with genital ulcers in the Dominican Republic and 63 in Peru underwent identical interviews and identical multiplex PCR (M-PCR) tests of genital lesion specimens for etiologic diagnoses. Algorithms for managing genital ulcers were developed. RESULTS: In the Dominican Republic, 5% were M-PCR-positive for, 26% for, and 43% for herpes simplex virus (HSV); in Peru, 10%, 5%, and 43%, respectively, were positive. The WHO algorithm for treating syphilis and chancroid had a sensitivity of 100%, a positive predictive value (PPV) of 24%, and an overtreatment rate of 76%. A modified algorithm for treating only those without vesicular lesions had 88% sensitivity and a 27% PPV, and the overtreatment rate was reduced to 58%. CONCLUSION: HSV caused 43% of genital ulcers in these populations. The modified algorithm had lower sensitivity but a reduced overtreatment rate. M-PCR testing was more sensitive than standard tests and more specific and sensitive than clinical diagnosis.

Population-based human papillomavirus prevalence in Lampang and Songkla, Thailand.

To investigate the prevalence and determinants of human papillomavirus (HPV) infection, the primary cause of cervical cancer, we studied 1741 women >/=15 years of age from Lampang and Songkla, Thailand. Exfoliated cervical cells were collected for Papanicolaou smear screening and DNA detection of 36 different HPV types. Serum immunoglobulin G antibodies against L1 virus-like particles (anti-VLPs) of HPV-16, -18, -31, -33, and -58 were evaluated using enzyme-linked immunosorbent assay. Overall, 110 women (6.3%) were HPV DNA positive; the most common types were HPV-16, -52, and -72. The age-standardized prevalence of HPV DNA was higher among the 1035 women from Lampang (9.1%; 95% confidence interval [CI], 7.1-11.1) than among the 706 women from Songkla (3.9%; 95% CI, 2.3%-5.6%). Anti-VLPs were found in 21.8% of all women and were more frequent among women from Lampang (29.2%) than among women from Songkla (10.9%). Major risk factors for cervical HPV DNA were age <35 years, HSV-2 seropositivity, and having a husband with extramarital sexual partners.