Herpes Simplex Virus Seropositivity Research Articles

Prior Herpes Simplex Virus Infection and the Risk of Herpes Zoster.

The incidence of herpes zoster (HZ) has increased in the United States concurrent with decrease in herpes simplex virus (HSV) prevalence. We hypothesized that lack of HSV-elicited cross-reactive immunity to varicella-zoster virus (VZV) results in an increased risk of HZ. Using specimens from the placebo arm of the Shingles Prevention Study, we investigated whether persons who develop HZ are less likely to have prior HSV infection than persons who do not develop HZ, and whether HZ is less severe in persons with HSV than in HSV seronegative persons. We conducted a nested case-control (1:2) study comparing the seroprevalence of HSV-1 and HSV-2 in cases (persons with polymerase chain reaction-confirmed HZ) to age-, sex-, and health-matched controls (persons without HZ). Sera from 639 study participants (213 cases and 426 controls) yielded definitive HSV antibody results and were analyzed. Overall, HSV seropositivity rate was 75%. HSV seronegativity was significantly higher in HZ cases than controls (30.5% vs 22.3%; P = .024), with a 55% higher risk of HZ in HSV seronegative than HSV seropositive participants. HSV seropositivity was associated with more severe HZ (P = .021). Our study demonstrated that prior infection with HSV partly protects against HZ.

Prevalence of herpes simplex virus types 1 and 2 antibodies among individuals screened in a tertiary hospital in the Eastern province of Saudi Arabia.

The epidemiology of herpes simplex virus (HSV) infections varies among populations depending on their demographic characteristics and exposure. This study describes the prevalence of HSV 1/2 IgG and IgM antibodies among individuals over a period of 5 years. A retrospective study was conducted to collect data on cases tested for HSV-1 and HSV-2 IgG and IgM antibodies for different medical conditions over five years between January 2014 and December 2018. 620 samples were tested for HSV 1/2 IgG and IgM during the study period. The total HSV seropositivity in the study population was 68% (422/620). The total seropositivity excluding children below 6 months of age was 65.3% (313/479). HSV-IgG seropositivity was significantly higher in married individuals (p<0.001, 95% CI 1.61-3.69). The HSV IgG seropositivity was significantly higher in children under the age of 6 months (N=109, 77.30%) than in children between 7 and 24 months old (27.6%) (Chi-square for linear trend, p<0.001), and it then tends to increase with age more than 24 months (Chi-square for linear trend, p=0.011). Eleven children showed laboratory evidence of recent HSV infection (6.2%) as indicated by HSV IgM antibodies and had diverse clinical conditions. HSV infection is highly prevalent in the Eastern Province of Saudi Arabia. Infection is most probably acquired during early childhood, and the tendency increases with age. However, a significant number of mothers are at risk of infection and transferring the infection to their fetuses.

Herpes Simplex Virus Seroprevalence among Pregnant Finnish Women and Their Spouses-A Six-Year Follow-Up Cohort Study.

The aim was to evaluate the herpes simplex virus (HSV) seroprevalence and seroconversion among 285 pregnant women and their 120 male spouses in Finland during a six-year follow-up (FU) between 1998–2008. We also studied the effect of sexual habits, pregnancy, and other demographic factors on the acquisition of HSV infection. Combined HSV-1 and HSV-2-IgG antibodies were assessed in the first baseline serum samples with an indirect enzyme immunoassay method. The individuals with seronegative or borderline HSV serology at baseline were additionally tested using their latest FU serum sample available. The overall HSV seroprevalence during the FU was 58.9% (168/285) among the women and 53.3% (64/120) among their spouses. The seroconversion rate was 11.4% (15/132) and 12.5% (8/64) among women and their spouses, respectively. Both spouses were HSV seropositive in 39.2% (47/120). To determine the HSV-2 seroprevalence, we also tested all HSV-seropositive participants using HSV-2-specific antigen. HSV-2 seropositivity was detected in 10.9% (44/405) of the participants. The age (p = 0.006) and history of genital warts (p = 0.006) of the women were associated with combined HSV-1 and/or HSV-2 seropositivity, while a younger age was related to HSV seroconversion (p = 0.023). Among the male spouses, HSV seropositivity was associated with the practice of oral sex (p = 0.033). To conclude, women of childbearing age acquire primary HSV infections and the presence of HSV in oral epithelium is common among HSV-seropositive individuals.

Seroprevalence of Herpes Simplex Virus Type 2 and Human Herpesvirus Type 8 among Prostate Cancer Patients Compared to Cancer-Free Men

Background: As one of the most prevalent cancers in men, prostate cancer is a condition with multiple causes. Viral infections have been identified as one of the major sources of elevated incidence of prostate cancer. Objectives: The purpose of this research was to assess the association of the risk of prostate cancer and its aggressiveness with seropositivity of herpes simplex virus 2 (HSV-2) and/or human herpesvirus 8 (HHV-8). Methods: Totally, 103 men with prostate cancer as cases and 81 healthy individuals as controls were included in this case-control analysis and provided a serum sample. The specific IgG antibodies against HSV-2 and HHV-8 were screened by enzyme-linked immunosorbent assay (ELISA). To determine the association between HSV-2, HHV-8, prostate-specific antigen (PSA) level, and demographic variables with incidence of prostate cancer, univariate and multivariate logistic regression models were applied. Results: The results of the univariate logistic regression model showed a statistically significant association between HSV-2 and HHV-8 seropositivity, PSA level, age, and smoking with prostate cancer incidence (P ≤ 0.20). The multivariate logistic regression model results after adjusting for the potential confounding variables showed a significant statistical association between the mean of PSA level [adjusted odds ratio (OR): 3.44; 95% CI: 2.15 - 5.51; P &lt; 0.001) and incidence of prostate cancer. Moreover, the results of univariate and multivariate logistic regression model showed a significant statistical association between age [adjusted OR: 0.88; 95% confidence interval (CI): 0.81 - 0.95; P = 0.001] and HSV-2 and also significant statistical association was found between PSA (adjusted OR: 1.02; 95% CI: 1.005 - 1.03; P = 0.006) and HHV-8. Conclusions: Although the seroprevalence of HSV-2 and HHV-8 was higher in patients with prostate cancer than in the control group, it cannot be concluded that there is a significant association between the seropositivity of these viruses and prostate cancer incidence. However, the findings showed a significant statistical association between age and seropositivity of HSV-2 and also a significant statistical association between PSA levels and seropositivity of HHV-8.

HSV-2 Infection as a Potential Cofactor for HIV Disease Progression and Selection of Drug Resistance Mutations in Adults under WHO-Recommended First-Line Antiretroviral Therapy: A Multicentric, Cross-Sectional Study in Cameroon, Central African Republic, Chad, and Gabon.

Although herpes simplex virus-2 (HSV-2) infection is a known cofactor for HIV transmission in Central Africa, its role in HIV disease progression is unclear. The aim of this study was to examine the potential link between HSV-2 infection and HIV disease progression, in addition to identifying the presence of genes conferring HIV antiretroviral resistance mutations. This was a cross-sectional study involving 302 HIV-infected adults in Central Africa with virological failure (viral load >1000 copies/mL) on first-line antiretroviral therapy from four different countries. The seroprevalence of HSV-2 was 32% (96/302). Amongst the HIV-infected individuals who were HSV-2 seropositive, the mean HIV viral load and CD4 count were 4.82 ± 0.83 log copies/mL and 243 ± 144 cells/microliter, respectively. Among the HIV-infected individuals who were HSV-2-seronegative, the mean HIV viral load and CD4 count were 3.48 ± 0.44 log copies/mL and 646 ± 212 cells/microliter, respectively (p < 0.001). There was a statistically significant relationship (p < 0.001) between HSV-2 seropositivity and the presence of resistance mutations to antiretrovirals (ARV), non-nucleoside reverse transcriptase inhibitors (NNRTI), and nucleoside reverse transcriptase inhibitors (NRTI) with odds ratios of 9.7, 10, and 11.9, respectively. There was no link between HSV-2 serostatus and protease inhibitor (PI) resistance mutations. There was a substantial accumulation of resistance mutations in HSV-2-seropositive compared to -seronegative patients. These findings support the link between HIV disease progression and HSV-2 infection. An association was observed between the presence of NNRTI and NRTI resistance mutations and HSV-2 seropositivity.

Maternal cytomegalovirus sero-positivity and autism symptoms in children.

Autism spectrum disorder (ASD) is one of the most commonly diagnosed neurodevelopmental disorders in the United States. While ASD can be significantly influenced by genetics, prenatal exposure to maternal infections has also been implicated in conferring risk. Despite this, the effects of several important maternal pathogens, such as cytomegalovirus (CMV) and herpes simplex virus 2 (HSV2), remain unknown. We tested whether maternal CMV and/or HSV2 sero-positivity was associated with ASD symptoms in children. ELISA was used to assay for CMV IgG and HSV2 IgG in serum from the mothers of 82 children whose ASD symptoms were assessed at 3-6years of age using the Social Responsiveness Scale version 2 (SRS-2). Associations between maternal viral serostatus and SRS-2 scores were estimated using linear regression with covariate adjustments. The children of mothers sero-positive for CMV, but not for HSV2, had SRS-2 scores 3.6-4.2 points higher, depending on the adjustment model, than sero-negative women, a significant finding, robust to several statistical adjustments. Our results suggest that maternal CMV infections may influence ASD symptoms. These findings are being further evaluated in ongoing prospective studies with larger population samples.

Preventive Strategies Against Cytomegalovirus and Incidence of α-Herpesvirus Infections in Solid Organ Transplant Recipients: A Nationwide Cohort Study.

We assessed the impact of antiviral preventive strategies on the incidence of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections in a nationwide cohort of transplant recipients. Risk factors for the development of HSV or VZV infection were assessed by Cox proportional hazards regression. We included 2781 patients (56% kidney, 20% liver, 10% lung, 7.3% heart, 6.7% others). Overall, 1264 (45%) patients received antiviral prophylaxis (ganciclovir or valganciclovir, n = 1145; acyclovir or valacyclovir, n = 138). Incidence of HSV and VZV infections was 28.9 and 12.1 cases, respectively, per 1000 person-years. Incidence of HSV and VZV infections at 1 year after transplant was 4.6% (95% confidence interval [CI] 3.5-5.8) in patients receiving antiviral prophylaxis versus 12.3% (95% CI 10.7-14) in patients without prophylaxis; this was observed particularly for HSV infections (3% [95% CI 2.2-4] versus 9.8% [95% CI 8.4-11.4], respectively). A lower rate of HSV and VZV infections was also seen in donor or recipient cytomegalovirus-positive patients receiving ganciclovir or valganciclovir prophylaxis compared with a preemptive approach. Female sex (hazard ratio [HR] 1.663, p = 0.001), HSV seropositivity (HR 5.198, p < 0.001), previous episodes of rejection (HR 1.95, p = 0.004), and use of a preemptive approach (HR 2.841, p = 0.017) were significantly associated with a higher risk of HSV infection. Although HSV and VZV infections were common after transplantation, antiviral prophylaxis significantly reduced symptomatic HSV infections.

Associations between excessive adiposity and seroprevalence of herpes simplex virus type 1 and type 2 among US adults: a population-based age–period–cohort analysis

ObjectivesEvidence on the association between herpes simplex virus (HSV) and excessive adiposity, such as obesity (body mass index ≥30 kg/m2) and abdominal obesity (waist circumference (WC) >102 or 88 cm),...

Seroepidemiological study of Herpes simplex virus 2 in human immuno deficiency virus-positive individuals attending a tertiary care hospital of South India

Background: Herpes Simplex Virus-2 (HSV-2) infection is widely studied and associated disease in human immuno deficiency virus-positive (HIV-positive) individuals. The diagnosis of HSV is difficult as the presentations are atypical. Studies have confirmed that HSV-2 infection increases the risk of HIV acquisition by 2-3 folds. The aim of the study was to estimate the seroprevalence of HSV-2 and its association with age, sex and behavioral characters among HIV-infected individuals attending a tertiary care hospital.Methods: Serum samples from 150 HIV positive patients were collected and screened for HSV-2 Ig G antibodies by indirect ELISA. The cut off index (COI) of each serum sample was determined by dividing the OD which was obtained for that serum sample, by the average OD of the cutoff serum. A COI below or equal to 1 was considered as negative and that above 1.1 was considered as positive.Results: The overall seroprevalence of HSV-2 in the study was 44% (95% CI: 36-52%) with more in men than women. Out of 92 men, 42 (45.65%) were HSV positive and 24 (41.38%) of 58 female were positive. Statistical significance was observed in participants who had past history of sexually transmitted disease and who had multiple sexual partners (≥11) making as risk factors for HSV-2 seropositivity. Genital herpes was reported in 41 of 150 participants and seropositivity was 51.22% indicating the lack of awareness and most of the infections are asymptomatic.Conclusions: Our study demonstrated a clear increase in seroprevalence of HSV-2 in HIV-infected individuals. Findings of our study have relevant public implications and strongly suggest the implementation of interventions in sexually transmitted infections to reduce the prevalence of HSV-2 and associated HIV transmission. As most of the infections of HSV are asymptomatic a continuous program for the screening of HSV in all cases of STD’s must be made to reduce the chances of acquisition of HIV and others.

Frequency of Oral Mucositis and Local Virus Reactivation in Herpes Simplex Virus Seropositive Children with Myelosuppressive Therapy.

Oral mucositis (OM) is a common chemo- and radiotherapy adverse effect in oncological pediatric patients. Herpes simplex virus (HSV) infection can cause a severe clinical course. We hypothesize, that HSV seropositivity is a risk factor for local HSV-1 reactivation and increased frequency of OM in patients with myelosuppressive therapies. We evaluated the prevalence of seropositivity of HSV-1 between June 2011 and April 2014 in patients with potential oncological disease and correlated it to the frequency of OM and local viral reactivation in OM under myelosuppressive therapy. The overall rate of HSV-seropositivity in our cohort was 22%. 48 patients underwent myelosuppressive therapy. Of these, 7 were HSV-1 IgG positive and 41 negative. All patients with OM under myelosuppressive therapy and positive local swab for viral HSV (l-PCR) were HSV-1 IgG positive before the start of therapy (100%). The absolute risk for OM in HSV-1 IgG positive patients was increased by 58.5% (95%CI: 20.0 - 72.2%) corresponding to a relative risk (RR) of 2.4 (95%CI: 1.7-3.5, P=0.009). The multivariable adjusted OR to suffer 2 or more OM episodes in HSV-1 IgG positivity was 8.8 (95%CI: 1.5-95.8, P=0.014). In HSV-1 IgG positive patients half of the OM episode showed HSV reactivation, and the risk for multiple OM episodes was increased. These patients should be investigated for HSV-infection in every OM episode. Prophylactic and preemptive therapeutic measures should be discussed early, but prospective data on HSV prophylaxis and preemptive treatment is required.

Partner-concurrency associated with herpes simplex virus 2 infection in young South Africans

Whilst much is known about the individual-level risk factors for herpes simplex virus 2 (HSV-2) infection, little is known about why only some populations develop generalized HSV-2 epidemics. This study aims to assess the extent to which partner-concurrency (a factor which operates at both the partnership- and network-level) may be responsible. We utilized multivariate logistic regression to analyse the relationship between HSV-2 seropositivity and potential risk factors in data from a representative cross-sectional survey of 14-24 year olds from a township in South Africa conducted in 1999. The overall prevalence of HSV-2 was 53.3% amongst women and 17% amongst men. For men, four factors remained significantly associated with HSV-2 infection in the multivariate regression analysis: total number of sex acts, being a migrant labourer, Zulu ethnicity and being human immunodeficiency virus (HIV) positive. For women, eight factors were associated with HSV-2 infection: increasing age, partner-concurrency (having a partner who had other partners), an older partner, total number of sex acts, using hormonal contraception, Xhosa ethnicity, syphilis seropositivity and being HIV positive. We conclude that partner-concurrency is associated with increased HSV-2 seropositivity in women.

Histopathology of Gastric Erosions Association with Etiological Factors and Chronicity

The histopathologic characteristics of the antral erosions, and a comparison with samples systematically collected from the background antral mucosa, have not been studied previously. Similarly, unknown is the association of these features with suspected etiological factors and chronicity of erosion. We studied 117 patients with gastric erosions in the absence of peptic ulcer disease. With 28 patients available for a follow-up 19 years later, sites of erosions and background mucosa were biopsied and histopathology of both independently assessed at both visits. Helicobacter pylori status was examined from the biopsies taken in the initial and follow-up gastroscopies. Only subjects originally displaying antral erosions were included. The presence of Herpes simplex virus (HSV) antibodies was analyzed and use of nonsteroidal anti-inflammatory drug (NSAID) was inquired. Initially, the inflammation was more active in the region of erosions than elsewhere in antral mucosa. More active inflammation in the erosion was associated with HSV seropositivity, Helicobacter pylori infection, and the recent use of NSAIDs. In the follow-up visit, antral erosions were present in 38% (3/8) of Helicobacter pylori negatives and in 35% (7/20) of positives (p = ns). The Helicobacter pylori positive subjects with chronic or recurrent erosions had initially higher scores of neutrophils compared to subjects with nonrecurrent or nonchronic erosions (2.7 ± 0.5 vs 1.2 ± 1.0; p = .002). Focally enhanced inflammation is characteristic for gastric erosions. This focal inflammation was associated with HSV seropositivity or NSAID use suggesting that such inflammation may be important in the pathogenesis of gastric antral erosions. Highly active inflammation in the erosions associates with their chronicity.

Association of GRIN1 and GRIN2A‐D With schizophrenia and genetic interaction with maternal herpes simplex virus‐2 infection affecting disease risk

N-methyl-D-aspartate (NMDA) receptors are very important for proper brain development and several lines of evidence support that hypofunction of the NMDA receptors are involved in the pathophysiology of schizophrenia. Gene variation and gene-environmental interactions involving the genes encoding the NMDA receptors are therefore likely to influence the risk of schizophrenia. The aim of this study was to determine (1) whether SNP variation in the genes (GRIN1, GRIN2A, GRIN2B, GRIN2C, and GRIN2D) encoding the NMDA receptor were associated with schizophrenia; (2) whether GRIN gene variation in the offspring interacted with maternal herpes simplex virus-2 (HSV-2) seropositivity during pregnancy influencing the risk of schizophrenia later in life. Individuals from three independently collected Danish case control samples were genotyped for 81 tagSNPs (in total 984 individuals diagnosed with schizophrenia and 1,500 control persons) and antibodies against maternal HSV-2 infection were measured in one of the samples (365 cases and 365 controls). Nine SNPs out of 30 in GRIN2B were significantly associated with schizophrenia. One SNP remained significant after Bonferroni correction (rs1806194, P(nominal) = 0.0008). Significant interaction between maternal HSV-2 seropositivity and GRIN2B genetic variation in the offspring were observed for seven SNPs and two remained significant after Bonferroni correction (rs1805539, P(nominal) = 0.0001 and rs1806205, P(nominal) = 0.0008). The significant associations and interactions were located at the 3' region of GRIN2B suggesting that genetic variation in this part of the gene may be involved in the pathophysiology of schizophrenia.

Infection with cytomegalovirus but not herpes simplex virus induces the accumulation of late-differentiated CD4+ and CD8+ T-cells in humans

Human cytomegalovirus (CMV) establishes persistent, usually asymptomatic, infection in healthy people. Because CMV infection is associated with the presence of lower proportions of peripheral naïve CD8+ T-cells and a higher fraction of late-differentiated CD8+ cells, commonly taken as biomarkers of age-associated compromised adaptive immunity ('immunosenescence'), we asked whether chronic exposure to any persistent virus mediates these effects. Herpes simplex virus (HSV) is also a widespread herpesvirus that establishes lifelong persistence, but, unlike CMV, its impact on the distribution of T-cell subsets has not been established. Here, we analysed T-cell subsets in 93 healthy people aged 42-81 years infected or not infected with CMV and/or HSV. Individuals harbouring CMV were confirmed to possess lower frequencies of naïve CD8+ T-cells (defined as CD45RA+CCR7+CD27+CD28+) and greater proportions of late-differentiated effector memory (CD45RA-CCR7-CD27-CD28-) and so-called TEMRA (CD45RA+CCR7-CD27-CD28-) CD4 and CD8 subsets, independent of HSV seropositivity. In CMV-seronegative donors, HSV did not affect T-cell subset distribution significantly. We conclude that these hallmarks of age-associated alterations to immune signatures are indeed observed in the general population in people infected with CMV and not those infected with a different persistent herpesvirus.

Cervical Human Papillomavirus Incidence and Persistence in a Cohort of HIV-Negative Women in Zimbabwe

Persistent infections with oncogenic human papillomavirus (HPV) types are causally related to cervical cancer. Little is known about the distribution of HPV types, independent risk factors of incidence and persistence, and patterns of persistence in sub-Saharan Africa. A cohort of 2040 Zimbabwean women was enrolled in a randomized trial assessing the effect of diaphragm/gel provision on human immunodeficiency virus and HPV acquisition. Data from the study arms were pooled for this analysis because diaphragm/gel provision did not affect HPV acquisition and clearance. Clinicians collected cervical samples for HPV testing at enrollment, 12 months, and exit (median 21 months). HPV prevalence was 24.5% for any HPV type and 16.1% for oncogenic types. HPV incidence at 12 months was 23.3% for any HPV type and 11.4% for oncogenic types. HPV58 had the highest baseline prevalence (5.0%) and incidence (2.4%). Type-specific persistence was 29.8% among all HPV infections over a median of 21 months of follow-up. Baseline predictors of incident HPV infection were younger age, having more than 1 lifetime sexual partner, infrequent condom use, herpes simplex virus-2 positive serology, and having a sexually transmissible infection or a different HPV type at enrollment. Baseline predictors of persistent HPV infection were younger age, having more than 1 lifetime sexual partner, and having a high-risk partner. The novel association between herpes simplex virus-2 seropositivity and incident HPV infection warrants further investigation. Having a high-risk partner is a potentially modifiable risk factor for persistent HPV infection. The relatively high prevalence of HPV58 has implications for vaccine development.

Seropositivity to Herpes Simplex Virus Antibodies and Risk of Alzheimer's Disease: A Population-Based Cohort Study

BackgroundHerpes Simplex Virus (HSV) infection has been proposed as a possible risk factor of Alzheimer's Disease (AD) notably because it is neurotropic, ubiquitous in the general population and able to establish lifelong latency in the host. The fact that HSV was present in elderly subjects with AD suggests that the virus could be a co-factor of the disease. We investigated the risk of developing AD in anti-HSV immunoglobulin G (IgG) positive subjects (indicator of a lifelong infection to HSV) and IgM-positive subjects (indicator of primary infection or reactivation of the virus) in a longitudinal population-based cohort of elderly subjects living in the community.MethodsCox proportional hazard models were used to study the risk of developing AD according to the presence or not of anti-HSV IgG and IgM antibodies, assessed in the sera of 512 elderly initially free of dementia followed for 14 years.ResultsDuring the follow-up, 77 incident AD cases were diagnosed. Controlled for age, gender, educational level and Apolipoprotein E4 (APOE4) status, IgM-positive subjects showed a significant higher risk of developing AD (HR = 2.55; 95% CI [1.38–4.72]), although no significant increased risk was observed in IgG-positive subjects (HR = 1.67; 95%CI [0.75–3.73]). No modification effect with APOE4 status was found.ConclusionReactivation of HSV seropositivity is highly correlated with incident AD. HSV chronic infection may therefore be contributive to the progressive brain damage characteristic of AD.

Obesity and the Likelihood of Sexual Behavioral Risk Factors for HPV and Cervical Cancer

Obesity is associated with higher cervical cancer mortality, but its relationship with sexual behavioral risk factors that predispose women to human papilloma virus (HPV) and cervical cancer is unclear. We used data from 3,329 women participants, aged 20-59 years, of the 1999-2004 National Health and Nutrition Examination Survey, to analyze the relationship between BMI and age at first intercourse, number of sexual partners, condom use during sexual activity, history of sexually transmitted disease (STD), herpes simplex virus 2 (HSV-2) seropositivity, and HPV prevalence. BMI was not associated with the prevalence of HPV. Mildly obese women (BMI 30.0-34.9 kg/m(2)) were least likely to report a STD history (9% vs. 13% in normal weight) and >or=2 sexual partners in the previous year (8% vs. 13%) while overweight women (BMI 25.0-29.9 kg/m(2)) were least likely to report >or=10 lifetime partners; among those with multiple partners, BMI was not associated with sexual activity without condoms in the past month. After adjustment for age, race/ethnicity, and education, women with higher BMI were less likely to report sexual behavioral risk factors than normal-weight women; however, odds ratios were only significant for mildly obese women for reporting a STD history (0.74, 95% confidence interval 0.55-0.99) and having >or=2 sexual partners in the last year (0.57, 0.39-0.85). Higher BMI was not associated with HSV-2 seropositivity after adjustment. HPV and sexual behavioral risk factors for HPV and cervical cancer are not more prevalent in obese than normal-weight women and unlikely to account for higher-observed cervical cancer mortality in obese women.

Worldwide Human Papillomavirus Etiology of Cervical Adenocarcinoma and Its Cofactors: Implications for Screening and Prevention

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. 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. 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. 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.

Association between Syphilis, Antibodies to Herpes Simplex Virus Type 2, and Recreational Drug Use and Hepatitis B Virus Infection in the Women's Interagency HIV Study

Liver disease is a leading cause of death in human immunodeficiency virus (HIV)-infected women; however, risk factors for hepatitis b virus (hbv) infection in this population have not been well studied. We describe the seroprevalence and predictors of HBV infection in a cross-sectional analysis of 2132 women with and at risk for HIV infection enrolled in the Women's Interagency HIV Study during the periods 1994-95 and 2001-02. Any test result positive for antibody to hepatitis B core antigen defined infection; those women with serological evidence of vaccine immunity were excluded from analysis. Women were stratified into those with a history of injection drug use (IDU), those with a history of noninjection drug use (non-IDU), and those with no history of illicit drug use. Of 1606 HIV-infected and 526 HIV-uninfected women, 7% and 12%, respectively, appeared to be vaccine immune. After exclusion of these women, 43% of 1500 HIV-infected and 22% of 461 HIV-uninfected women had HBV infection. HBV infection prevalence differed among the IDU, non-IDU, and no illicit drug use groups (76%, 30%, and 17%, respectively; P<.0001). HBV infection was strongly associated with herpes simplex virus 2 (HSV-2) seropositivity in the IDU group (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.6-5.4) and with a history of syphilis in the non-IDU group (OR, 2.7; 95% CI, 1.4-5.0). We found a high prevalence of HBV infection in our cohort of women with and at risk for HIV infection. HSV-2 seropositivity and a history of syphilis appeared to be important correlates of HBV infection. Sexual transmission of HBV, particularly in those with a history of genital ulcer disease, should be a major focus of education in all high-risk groups.

A population based study of herpes simplex virus 2 seroprevalence in rural Costa Rica

Objectives: To determine seroprevalence and determinants of herpes simplex virus 2 (HSV-2) seropositivity, in a random sample of a population based cohort of 10 049 women of Guanacaste, Costa Rica,...