Henrike J. Vriend

Patterns of human papillomavirus DNA and antibody positivity in young males and females, suggesting a site-specific natural course of infection.

Background To monitor the impact of human papillomavirus types 16 and 18 vaccine on HPV infection dynamics in the Netherlands, we started an ongoing study in sexually transmitted infection (STI) clinics in 2009. Here, we analyze baseline type-specific HPV DNA and HPV-specific antibody positivity rates. Methods We enrolled 3569 men and women, 16–24 years of age, from 14 STI clinics, and estimated genital and anal HPV DNA and antibody positivity rates of 7 main carcinogenic HPV types. Generalized estimating equations regression analyses were applied to determine risk factors for, and associations between, type-specific HPV DNA and antibody positivity. Results Genital HPV DNA positivity rates were higher in women than in men; anal HPV DNA was especially high in men who have sex with men (MSM). HPV antibody seropositivity rates were also highest in women and MSM. High-risk sexual behavior was predictive of both HPV DNA and antibody positivity. Despite a strong correlation in serological profiles for multiple HPV types, seropositivity was independently associated with homologous HPV DNA detection. Conclusions HPV DNA and antibody positivity rates are higher in women and MSM than in heterosexual men, but their association is similar across gender. This suggests a site-specific natural course of infection.

Hepatitis C virus prevalence in The Netherlands: migrants account for most infections

A population-based anti-hepatitis C virus (HCV) prevalence is important for surveillance purposes and it provides insight into the burden of disease. The outcomes of recent studies in the general Dutch population as well as recent HCV data from specific risk groups including migrants, men who have sex with men (MSM) and injecting drug users (IDUs), were implemented in a modified version of the Workbook Method (a spreadsheet originally designed for HIV estimations), to estimate Dutch HCV seroprevalence. The estimated national seroprevalence of HCV was 0·22% (min 0·07%, max 0·37%), corresponding to 28 100 (min n = 9600, max n = 48 000) HCV-infected individuals in The Netherlands. Of these, first-generation migrants from HCV-endemic countries (HCV prevalence ≥2%) accounted for the largest HCV-infected group, followed by IDUs and HIV-positive MSM.

Hepatitis C in the general population of various ethnic origins living in the Netherlands: should non-Western migrants be screened?

BACKGROUND & AIMS Little is known about the HCV prevalence in non-Western migrant populations. To determine whether targeted HCV screening and prevention programs for migrants are needed, we examined HCV prevalence and determinants among non-Western, Western migrants, and the native Dutch population in the Netherlands. METHODS Data were obtained from four surveys: (1) 3895 heterosexual visitors recruited during biannual surveys at the STI-clinic Amsterdam, 2007-2009; (2) random sample of 4563 pregnant women in Amsterdam, 2003; (3) population-based random sample of 1309 inhabitants of Amsterdam, 2004; (4) population-based random sample of 4428 people living in the Netherlands, 2006-2007. Characteristics associated with HCV-positivity were examined and phylogenetic analysis was used to obtain insight in the geographical origin of HCV strains. RESULTS HCV seroprevalence in the four surveys was low (0.3-0.6%). In total 4860/14,195 (34%) were non-Western and 9329/14,195 (66%) Western participants (including Dutch). First-generation non-Western migrants were more likely to be HCV-positive (0.7-2.3%) than Western participants (0.1-0.4%). Except for survey 3, second-generation non-Western migrants had a lower HCV prevalence than first-generation migrants, comparable to Western migrants and the Dutch population. Phylogenetic analysis showed that the majority of the HCV-positive, first-generation non-Western non-European migrants were infected with endemic strains which are rarely observed in Europe. CONCLUSIONS First-generation non-Western migrants are at increased risk for HCV. Phylogenetic analysis suggests that transmission likely took place in the country of origin, causing introduction but no further transmission of endemic HCV strains in the Netherlands. HCV screening and prevention programs should target first-generation, but not second-generation, non-Western migrants.

Hepatitis C virus seroprevalence in The Netherlands

A population-based anti-hepatitis C virus (HCV) prevalence is important for surveillance purposes and it provides an insight into the burden of disease. In The Netherlands, a recent HCV seroprevalence estimate is not available. This national population-based cross-sectional serosurvey (PIENTER-2) resulted in a weighted national HCV seroprevalence of 0.30% (95% confidence interval 0.05-0.55%). About 70% of the HCV positive individuals found were born in an HCV-endemic country.

Type-specific human papillomavirus infections among young heterosexual male and female STI clinic attendees

Background: Baseline genotype-specific human papillomavirus (HPV) prevalence rates and associated risk factors per gender enable future assessment of the impact of vaccination on HPV dynamics. Methods: Before the start of national HPV vaccination for girls, data were collected cross-sectionally in nationwide Dutch sexually transmitted infections (STI) clinics among heterosexual males (n = 430) and females (n = 1136) aged 16 to 24 years. Self-collected vaginal or penile swabs were analyzed by a sensitive polymerase chain reaction (SPF10) and genotyped with line probe assay. Logistic regression was applied to estimate determinants of HPV prevalent infections. Results: HPV prevalence was 54% among males and 72% among females. High-risk (HR) HPV was present in males and females, 40% and 58%, respectively. Independent risk factors for HR-HPV infection were female gender, number of lifetime sex partners and a history of chlamydia or gonorrhea. In addition, not having a casual partner and consistent condom use were protective factors in women, but not in men. For low-risk (LR) HPV, the odds were smaller. Multiple HR-HPV and sexual risk behavior showed a stronger association compared with a single HR-HPV infection. Conclusions: Prevalence of HR-HPV is high in both genders. Infection with multiple HR-HPV types was more associated with high-risk sexual behavior than infection with LR-HPV types or a single HR-HPV type.

Incidence and persistence of carcinogenic genital human papillomavirus infections in young women with or without Chlamydia trachomatis co-infection.

We assessed whether infection with chlamydia increases the incidence of carcinogenic human papillomavirus (HPV) infections and if HPV persistence is affected by chlamydia co‐infection. For 1982 women (16–29 years‐old) participating in two consecutive rounds of a chlamydia screening implementation trial, swabs were polymerase chain reaction tested to detect chlamydia and 14 carcinogenic HPV genotypes. HPV type‐specific incidence and persistence rates were stratified for chlamydia positivity at follow‐up. Associations were assessed by multilevel logistic regression analyses with correction for sexual risk factors. HPV type‐specific incidence ranged from 1.4% to 8.9% and persistence from 22.7% to 59.4% after a median follow‐up of 11 months (interquartile range: 11–12). Differences in 1‐year HPV persistence rates between chlamydia ‐infected and noninfected women were less distinct than differences in HPV incidence rates (pooled adjusted odds ratios of 1.17 [95% CI: 0.69–1.96] and 1.84 [95% CI: 1.36–2.47], respectively). The effect of chlamydia co‐infection on HPV‐infection risk did not significantly differ by HPV genotype. In conclusion, infection with chlamydia increases the risk of infection by carcinogenic HPV types and may enhance persistence of some HPV types. Although these findings could reflect residual confounding through unobserved risk factors, our results do give reason to explore more fully the association between chlamydia and HPV type‐specific acquisition and persistence.

Sexually transmitted infections screening at HIV treatment centers for MSM can be cost-effective.

Objective:To estimate the cost-effectiveness of anorectal chlamydia screening among men who have sex with men (MSM) in care at HIV treatment centers. Design:Transmission model combined with economic analysis over a 20-year period. Setting and participants:MSM in care at HIV treatment centers. Intervention:Once-yearly or twice-yearly screening for anorectal chlamydia among MSM in care at HIV treatment centers. Main outcome measures:Averted HIV and chlamydia infections; discounted quality-adjusted life-years and costs; incremental cost-effectiveness ratio (ICER). Results:Costs will be saved by routine chlamydia screening of MSM in care at HIV treatment centers if these patients seek little or no screening elsewhere. Nonroutine screening is considerably more expensive than routine screening offered within a scheduled visit. Adding once-yearly chlamydia screening for MSM in care at HIV treatment centers is cost saving when 30% or fewer of those men seek once-yearly screening elsewhere (&OV0556;1.5 to &OV0556;8.1 million saved). Twice-yearly routine screening at HIV treatment centers is cost-effective only when routine screening takes place without additional nonroutine screening (&OV0556;1.9 million saved). Conclusions:Adding annual chlamydia screening to the HIV consultation will be cost saving as long as only a limited proportion of men are nonroutinely screened. The ICER was most sensitive to the percentage of MSM that continue to be screened elsewhere.

Repeated STI and HIV testing among HIV-negative men who have sex with men attending a large STI clinic in Amsterdam: a longitudinal study

Objective In the Netherlands, men who have sex with men (MSM) are advised via informal guidelines to test for STI at least annually. We estimated the proportion of HIV-negative MSM testing repeatedly at 12-month or smaller intervals at a large STI clinic in the Netherlands. In addition, we explored whether repeated testing is related to risk behaviour. Design and methods Longitudinal data of HIV-negative MSM visiting the Amsterdam STI clinic between 2009 and 2012 were analysed. To estimate the timing of repeated testing, Kaplan–Meier methods were used. Determinants for repeated testing (distinguishing testing at 12-month or smaller intervals and less than 12-monthly testing, with single testers as reference group) were identified using multivariate multinomial logistic regression analyses. Results In total, 19 479 consultations of 9174 HIV-negative MSM were identified. Of these MSM, 35% (95% CI 33% to 36%) were estimated to return to the STI clinic within 1 year following baseline consultation. Among 1767 men with at least two consultations and at least 2 years between baseline and last consultation, 43% tested repeatedly at 12-month or smaller intervals in those first 2 years. Repeated testers reported higher sexual risk behaviour (ie, only casual or both casual and steady sex partners, higher numbers of sex partners) at baseline compared with single testers. This effect tended to be slightly stronger for men testing repeatedly at 12-month or smaller intervals. Conclusions The proportion of MSM testing for STI annually is low. MSM testing repeatedly had higher baseline levels of risk behaviour. Strategies to motivate MSM to test annually should be explored.

Population- and Type-Specific Clustering of Multiple HPV Types Across Diverse Risk Populations in the Netherlands

In view of possible type replacement upon introduction of human papillomavirus (HPV) vaccination, we aimed to explore patterns of type-specific clustering across populations with various background infection risks. A total of 3,874 women from 3 cross-sectional studies in the Netherlands (in 2007-2009) provided vaginal self-samples, which were tested for 25 HPV genotypes by a sensitive molecular assay (SPF10 line probe assay, DDL Diagnostic Laboratory, Voorburg, the Netherlands). The number of concurrent HPV infections per woman was studied by Poisson regression. Associations between HPV types were investigated by generalized estimating equation analyses. The prevalence of any HPV type was 14% in a population-based study, 54% in a chlamydia screening intervention study, and 73% in a study among attendees of sexually transmitted infection clinics. Overall, multiple HPV infections were detected in 26% of the women. The number of concurrent HPV infections conformed to an overdispersed Poisson distribution, even after correction for known risk factors. Types differed significantly in their tendencies to be involved in coinfections, but no evidence for particular type-type interactions was found. Moreover, the strongest associations were observed in the lowest-risk population and vice versa.We found no indications of pairwise interactions, but our findings do suggest that clustering differs among HPV types and varies across risk groups.

Genetic Diversity in the Major Capsid L1 Protein of HPV-16 and HPV-18 in the Netherlands.

Objectives Intratypic molecular variants of human papillomavirus (HPV) type-16 and -18 exist. In the Netherlands, a bivalent vaccine, composed of recombinant L1 proteins from HPV-16 and -18, is used to prevent cervical cancer since 2009. Long-term vaccination could lead to changes in HPV-16 and -18 virus population, thereby hampering vaccination strategies. We determined the genetic diversity of the L1 gene in HPV-16 and -18 viral strains circulating in the Netherlands at the start of vaccination in order to understand the baseline genetic diversity in the Dutch population. Methods DNA sequences of the L1 gene were determined in HPV-16 (n = 241) and HPV-18 (n = 108) positive anogenital samples collected in 2009 and 2011 among Dutch 16- to 24-year old female and male attendees of the sexually transmitted infection (STI) clinics. Phylogenetic analysis was performed and sequences were compared to reference sequences HPV-16 (AF536179) and HPV-18 (X05015) using BioNumerics 7.1. Results For HPV-16, ninety-five single nucleotide polymorphism (SNPs) were identified, twenty–seven (28%) were non-synonymous variations. For HPV-18, seventy-one SNPs were identified, twenty-nine (41%) were non-synonymous. The majority of the non-silent variations were located in sequences encoding alpha helix, beta sheet or surface loops, in particular in the immunodominant FG loop, and may influence the protein secondary structure and immune recognition. Conclusions This study provides unique pre-vaccination/baseline data on the genetic L1 diversity of HPV-16 and -18 viruses circulating in the Netherlands among adolescents and young adults.