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Papers by Audrey King

Vaccine, May 1, 2015

In Japan, government support for human papillomavirus (HPV) vaccination began in November 2010. H... more In Japan, government support for human papillomavirus (HPV) vaccination began in November 2010. However, the mass media repeatedly reported on severe adverse events. The Japanese Ministry of Health, Labor and Welfare suspended proactive recommendations for HPV vaccines in June 2013. Japan's HPV vaccination rate dropped from 70% to less than 1% in 2017. We examined cervical cancer screening results in terms of abnormal cytology, histology, and HPV vaccination status among 11,903 women aged 20 to 25 y in the fiscal year 2015. The overall rate of HPV vaccination was 26.1% (3,112/11,903). Regarding cytology, the rate of atypical squamous cells of undetermined significance (ASC-US) or worse was 3.3% (103/3,112) in women who received HPV vaccination (vaccine (+) women) and 5.6% (496/8,791) in women who did not (vaccine (-) women). The rate of highgrade squamous intraepithelial lesion (HSIL) or worse was 0.26% (8/3,112) in vaccine (+) women and 0.81% (72/8,791) in vaccine (-) women. Regarding histology, the rate of cervical intraepithelial neoplasia 1 or worse (CIN1+) was 1.4% (42/3,112) in vaccine (+) women and 2.1% (178/8,791) in vaccine (-) women. The rates of CIN2+ and CIN3+ were similar regardless of vaccination. We found a significantly lower incidence of CIN in vaccine (+) women. These results suggest that the resumption of recommending HPV vaccination as primary prevention for cervical cancer is needed in Japan.

Vaccine, Apr 1, 2020

Introduction: In 2009, girls-only HPV16/18 vaccination was introduced in the Netherlands which ha... more Introduction: In 2009, girls-only HPV16/18 vaccination was introduced in the Netherlands which has achieved 46-61% uptake. Heterosexual men have benefitted from herd protection, but it is unknown whether men who have sex with men (MSM) also benefit from herd effects of the girls-only HPV16/18 vaccination program. Because MSM bear a high HPV-related disease burden, countries might consider targeted vaccination for MSM. To study possible herd effects and prior HPV exposure at a potential moment of vaccination, we assessed trends in the HPV prevalence and proportions (sero)negative for the various vaccine types among young MSM visiting sexual health centers (SHCs). Methods: We used data from MSM included in PASSYON study years 2009-2017. In this biennial crosssectional study among visitors of SHCs aged 16-24 years, MSM provided a penile and anal swab for HPV DNA testing (including vaccine types HPV6

The Journal of Infectious Diseases, Jan 9, 2020

The bivalent human papillomavirus (HPV) vaccine is highly effective and induces robust serologica... more The bivalent human papillomavirus (HPV) vaccine is highly effective and induces robust serological responses. Using a Dutch prospective cohort initiated in 2009, including 744 vaccinated and 294 unvaccinated girls (1993-1994) who provide a vaginal self-swab sample, serum sample, and questionnaire yearly, we report a high, persisting antibody response up to 9 years after vaccination for vaccine types HPV-16 or HPV-18. Antibodies against nonvaccine HPV types 31, 33, 45, 52, and 58 were lower but still significantly higher than in unvaccinated individuals. This was also reflected in the seroprevalence. We compared participant characteristics and antibody levels between vaccinated women with and those without HPV infections 1 year before infection (204 incident and 64 persistent infections), but we observed no consistent difference in type-specific antibody levels. Having a high-risk HPV infection was associated with sexual risk behavior and smoking 1 year before infection. Although high antibody levels are necessary for protection, our study suggests that on the individual level other factors such as HPV exposure or antibody avidity could be important.

BMC Genomics, 2008

Background: Whooping cough caused by Bordetella pertussis in humans, is re-emerging in many count... more Background: Whooping cough caused by Bordetella pertussis in humans, is re-emerging in many countries despite vaccination. Several studies have shown that significant shifts have occurred in the B. pertussis population resulting in antigenic divergence between vaccine strains and circulating strains and suggesting pathogen adaptation. In the Netherlands, the resurgence of pertussis is associated with the rise of B. pertussis strains with an altered promoter region for pertussis toxin (ptxP3). Results: We used Multi-Locus Sequence Typing (MLST), Multiple-Locus Variable Number of Tandem Repeat Analysis (MLVA) and microarray-based comparative genomic hybridization (CGH) to characterize the ptxP3 strains associated with the Dutch epidemic. For CGH analysis, we developed an oligonucleotide (70-mers) microarray consisting of 3,581 oligonucleotides representing 94% of the gene repertoire of the B. pertussis strain Tohama I. Nine different MLST profiles and 38 different MLVA types were found in the period 1993 to 2004. Forty-three Dutch clinical isolates were analyzed with CGH, 98 genes were found to be absent in at least one of the B. pertussis strains tested, these genes were clustered in 8 distinct regions of difference. Conclusion: The presented MLST, MLVA and CGH-analysis identified distinctive characteristics of ptxP3 B. pertussis strains-the most prominent of which was a genomic deletion removing about 23,000 bp. We propose a model for the emergence of ptxP3 strains.

PLOS ONE, Jun 11, 2013

Bordetella pertussis (B. pertussis) is the causative agent of whooping cough, which is a highly c... more Bordetella pertussis (B. pertussis) is the causative agent of whooping cough, which is a highly contagious disease in the human respiratory tract. Despite vaccination since the 1950s, pertussis remains the most prevalent vaccine-preventable disease in developed countries. A recent resurgence pertussis is associated with the expansion of B. pertussis strains with a novel allele for the pertussis toxin (ptx) promoter ptxP3 in place of resident ptxP1 strains. The recent expansion of ptxP3 strains suggests that these strains carry mutations that have increased their fitness. Compared to the ptxP1 strains, ptxP3 strains produce more Ptx, which results in increased virulence and immune suppression. In this study, we investigated the contribution of gene expression changes of various genes on the increased fitness of the ptxP3 strains. Using genome-wide gene expression profiling, we show that several virulence genes had higher expression levels in the ptxP3 strains compared to the ptxP1 strains. We provide the first evidence that wildtype ptxP3 strains are better colonizers in an intranasal mouse infection model. This study shows that the ptxP3 mutation and the genetic background of ptxP3 strains affect fitness by contributing to the ability to colonize in a mouse infection model. These results show that the genetic background of ptxP3 strains with a higher expression of virulence genes contribute to increased fitness.

Infection and Immunity, Jul 1, 2004

Bordetella pertussis is reemerging in several countries with a traditionally high vaccine uptake.... more Bordetella pertussis is reemerging in several countries with a traditionally high vaccine uptake. An analysis of clinical isolates revealed antigenic divergence between vaccine strains and circulating strains with respect to P.69 pertactin. Polymorphisms in P.69 pertactin are mainly limited to regions comprised of amino acid repeats, designated region 1 and region 2. Region 1 flanks the RGD motif, which is involved in adherence. Although antibodies against P.69 pertactin are implicated in protective immunity, little is known about the structure and location of its epitopes. Here we describe the identification by pepscan analysis of the locations of mainly linear epitopes recognized by human sera and mouse monoclonal antibodies (MAbs). A total of 24 epitopes were identified, and of these only 2 were recognized by both MAbs and human antibodies in serum. A number of immunodominant epitopes were identified which were recognized by 78 to 93% of the human sera tested. Blocking experiments indicated the presence of high-avidity human antibodies against conformational epitopes. Human antibodies against linear epitopes had much lower avidities, as they were unable to block MAbs. Pepscan analyses revealed several MAbs which bound to both region 1 and region 2. The two regions are separated by 289 amino acids in the primary structure, and we discuss the possibility that they form a single conformational epitope. Thus, both repeat regions may serve to deflect the immune response targeted to the functional domain of P.69 pertactin. This may explain why the variation in P.69 pertactin is so effective, despite the fact that it is limited to only two small segments of the molecule.

BMC Genomics, 2010

Background: Bordetella pertussis is the causative agent of human whooping cough (pertussis) and i... more Background: Bordetella pertussis is the causative agent of human whooping cough (pertussis) and is particularly severe in infants. Despite worldwide vaccinations, whooping cough remains a public health problem. A significant increase in the incidence of whooping cough has been observed in many countries since the 1990s. Several reasons for the re-emergence of this highly contagious disease have been suggested. A particularly intriguing possibility is based on evidence indicating that pathogen adaptation may play a role in this process. In an attempt to gain insight into the genomic make-up of B. pertussis over the last 60 years, we used an oligonucleotide DNA microarray to compare the genomic contents of a collection of 171 strains of B. pertussis isolates from different countries. Results: The CGH microarray analysis estimated the core genome of B. pertussis, to consist of 3,281 CDSs that are conserved among all B. pertussis strains, and represent 84.8% of all CDSs found in the 171 B. pertussis strains. A total of 64 regions of difference consisting of one or more contiguous CDSs were identified among the variable genes. CGH data also revealed that the genome size of B. pertussis strains is decreasing progressively over the past 60 years. Phylogenetic analysis of microarray data generated a minimum spanning tree that depicted the phylogenetic structure of the strains. B. pertussis strains with the same gene content were found in several different countries. However, geographic specificity of the B. pertussis strains was not observed. The gene content was determined to highly correlate with the ptxP-type of the strains. Conclusions: An overview of genomic contents of a large collection of isolates from different countries allowed us to derive a core genome and a phylogenetic structure of B. pertussis. Our results show that B. pertussis is a dynamic organism that continues to evolve.

PLOS ONE, Sep 19, 2007

Background. Bordetella pertussis is a Gram-negative bacterium that infects the human respiratory ... more Background. Bordetella pertussis is a Gram-negative bacterium that infects the human respiratory tract and causes pertussis or whooping cough. The disease has resurged in many countries including Finland where the whole-cell pertussis vaccine has been used for more than 50 years. Antigenic divergence has been observed between vaccine strains and clinical isolates in Finland. To better understand genome evolution in B. pertussis circulating in the immunized population, we developed an oligonucleotide-based microarray for comparative genomic analysis of Finnish strains isolated during the period of 50 years. Methodology/Principal Findings. The microarray consisted of 3,582 oligonucleotides (70-mer) and covered 94% of 3,816 ORFs of Tohama I, the strain of which the genome has been sequenced [1]. Twenty isolates from 1953 to 2004 were studied together with two Finnish vaccine strains and two international reference strains. The isolates were selected according to their characteristics, e.g. the year and place of isolation and pulsed-field gel electrophoresis profiles. Genomic DNA of the tested strains, along with reference DNA of Tohama I strain, was labelled and hybridized. The absence of genes as established with microarrays, was confirmed by PCR. Compared with the Tohama I strain, Finnish isolates lost 7 (8.6 kb) to 49 (55.3 kb) genes, clustered in one to four distinct loci. The number of lost genes increased with time, and one third of lost genes had functions related to inorganic ion transport and metabolism, or energy production and conversion. All four loci of lost genes were flanked by the insertion sequence element IS481. Conclusion/Significance. Our results showed that the progressive gene loss occurred in Finnish B. pertussis strains isolated during a period of 50 years and confirmed that B. pertussis is dynamic and is continuously evolving, suggesting that the bacterium may use gene loss as one strategy to adapt to highly immunized populations.

Journal of Clinical Microbiology, Jun 1, 2002

Despite more than 50 years of vaccination, Bordetella pertussis has remained endemic in The Nethe... more Despite more than 50 years of vaccination, Bordetella pertussis has remained endemic in The Netherlands, causing epidemic outbreaks every 3 to 5 years. Strain variation may play a role in the persistence of B. pertussis and was studied by sequencing 15 genes coding for surface proteins, including genes for all five components of acellular pertussis vaccines: pertussis toxin (Ptx), pertactin (Prn), filamentous hemagglutinin, and fimbriae (Fim2 and Fim3). A low level of allelic variation was observed, confirming a recent evolutionary origin of B. pertussis. In modern isolates, polymorphism was observed only in prn, ptxS1, ptxS3, and tcfA. Polymorphism in ptxS1, ptxS3, and tcfA was used to categorize isolates in multilocus sequence types (MLSTs). Analysis of Dutch isolates from 1949 to 1999 revealed five MLSTs, which showed a highly dynamic temporal behavior. We observed significant changes in the MLSTs after the introduction of pertussis vaccination in The Netherlands. Epidemic years were found to be associated with the expansion of MLST-4 or MLST-5. MLST-5 showed a remarkable expansion from 10% in 1997 to 80% in 1999. The MLST analysis was extended to a number of widely separated geographic regions: Finland, Italy, Japan, and the United States. MLST-4 and MLST-5 were found to dominate in Italy and the United States. In Finland and Japan, MLST-3 and MLST-2, respectively, were predominant. Thus, although each region showed distinctive MLST frequencies, in three of the five regions MLST-4 and MLST-5 were predominant. These types may represent newly emerged, successful clones. The identification of highly successful clones may shed light on the question of how B. pertussis is able to maintain itself in vaccinated populations.

Journal of Clinical Microbiology, 2020

Human papillomavirus (HPV) epidemiological and vaccine studies require highly sensitive HPV detec... more Human papillomavirus (HPV) epidemiological and vaccine studies require highly sensitive HPV detection systems. The widely used broad-spectrum SPF 10 -DEIA-LiPA 25 (SPF 10 method) has reduced sensitivity toward HPV-45 and -59. Therefore, anogenital samples from the PASSYON study were retrospectively analyzed with type-specific (TS) HPV-45 and -59 real-time quantitative PCR (qPCR) assays. The SPF 10 method missed 51.1% of HPV-45 and 76.1% of HPV-59 infections that were detected by the TS qPCR assays.

Clinical Infectious Diseases, 2020

Background Human papillomavirus (HPV) vaccination programs achieve substantial population-level i... more Background Human papillomavirus (HPV) vaccination programs achieve substantial population-level impact, with effects extending beyond protection of vaccinated individuals. We assessed trends in HPV prevalence up to 8 years postvaccination among men and women in the Netherlands, where bivalent HPV vaccination, targeting HPV types 16/18, has been offered to (pre)adolescent girls since 2009 with moderate vaccination coverage. Methods We used data from the PASSYON study, a survey initiated in 2009 (prevaccination) and repeated biennially among 16- to 24-year-old visitors of sexual health centers. We studied genital HPV positivity from 2009 to 2017 among women, heterosexual men, and unvaccinated women using Poisson generalized estimating equation models, adjusted for individual- and population-level confounders. Trends were studied for 25 HPV types detected by the SPF10-LiPA25 platform. Results A total of 6354 women (64.7% self-reported unvaccinated) and 2414 heterosexual men were includ...

Under the National Immunisation Programme (NIP), 1,520,301 children and pregnant women were vacci... more Under the National Immunisation Programme (NIP), 1,520,301 children and pregnant women were vaccinated in the Netherlands in 2019. Together, they received a total of 2,929,264 vaccinations. National immunisation coverage rose slightly for the first time in five years. In 2019, there were no notifications for diphtheria, tetanus, rubella, and polio. As in previous years, the number of notifications was low for Haemophilus influenzae type b (Hib; 39). The number of measles notifications was relatively high (84). The number of mumps cases (131) was double the number reported in the previous year. The number of notifications of hepatitis B (1205) remained stable. The number of notifications of meningococcal W disease (62) decreased after introduction of MenACWY-vaccination into the NIP (for 14-month-olds and 14-year-olds). This ended the rise in notifications from 2015 to 2018 (from 9 to 103). The number of pertussis notifications (6383) increased compared with 2018. Since the end of 20...

Sexually Transmitted Infections, 2013

Oral sessions Results Seropositivity for any of the 15 HPV types was 65.7%, any of the 11 hr-HPV ... more Oral sessions Results Seropositivity for any of the 15 HPV types was 65.7%, any of the 11 hr-HPV types 59.2%, and any of the four lr-HPV types 33.1%. Antibodies against multiple HPV types were more common (45.3%) than against single HPV types (20.4%). Antibodies against at least one of the four vaccine HPV types (HPV 6, 11, 16, and 18) were detected in 40.8% women. Among hr-HPV types seropositivity was the highest for HPV 16 (25.2%) and among lr-HPV types for HPV 6 (19.1%). Age-specific seropositivity for HPV 16 was the highest among 30-39 years old women (29.6%) and decreased with increasing age to 14.0% among 60-64 years old women (p = 0.014). Seropositivity for any of the hr-HPV among women with pathological cytology was 76.8% and those negative for intraepithelial lesion or malignancy 58.3% (p < 0.001). Conclusion Our results show a substantial burden of lifetime sexual exposure to these 15 HPV types before the introduction of vaccination and also a relatively high cumulative exposure to at least one of the four vaccine HPV types. Thus, vaccination of females before sexual debut with a quadrivalent HPV vaccine has a potential to contribute to a substantial reduction of the burden of cervical infections and cervical cancer as well as some other HPV related morbidity, including genital warts. Our data also present the baseline for monitoring HPV long-term vaccination impact.

Poster Presentations, 2019

Results 28 interviews were conducted (15 MSMO, 13 MSMW). Half of MSMW reported predominantly male... more Results 28 interviews were conducted (15 MSMO, 13 MSMW). Half of MSMW reported predominantly male partners and half predominantly female. MSMO viewed STIs as "an annoying reality of life" and both groups had positive perceptions of STI testing; however, MSMW described more STI stigma and less frequent testing. MSMO and MSMW who were more involved with the queer community had better sexual health knowledge. Many MSMW noted it was easier to have sexual health discussions with male partners; however, many also described the pressure of condom use, "with men, [was] to not use a condom a fair bit of time and probably by women, [was] to use a condom." There was significant fear in both groups about disclosing sexual practices to general practitioners and some MSMW preferred the anonymity of specialist sexual health clinics. Biphobia and bisexual erasure were frequently discussed by both groups. Conclusion MSMW described less comprehensive sexual health knowledge and more barriers to accessing sexual health care. Service provision and health promotion messaging must be broadened to capture the reality of increasing sexual fluidity. Destigmatising MSM behaviour and sexual health discussions, particularly in primary care, is crucial to ensuring all people receive appropriate sexual health care. Disclosure No significant relationships.

Poster Presentations, 2019

Background Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most common pathogen... more Background Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most common pathogens causing genital tract infections. They cause a significant global morbidity and mortality and have been associated with increased risk of HIV transmission, mainly among key populations fueling STIs and HIV. Men who have sex with men (MSM) had been classified by the Moroccan National AIDS Program (NAP) as a vulnerable risky group with higher burden of STIs. The aim of the present study is to assess the prevalence of CT and NG among MSM in Marrakech. Methods From October to December 2017, a total of 238 MSM were enrolled in the study using Respondent-Driven Sampling (RDS). Access to this population was facilitated by an NGO evolving in the field of HIV and STIs, with extensive experience with hard-to-reach population. Eligible recruits were aged of 18 years and older and having lived in Marrakech for the previous six months. Socio-demographic and behavioral factors were collected using a structured questionnaire. CT and NG investigations were performed using the molecular test the Xpert CT/NG tests (Cepheid, USA) on anal swab samples. Results The findings showed a prevalence of CT and NG of 9.24% (22/238) and 8.40 (20/238) respectively. A CT/NG coinfection was found in 3.36% (8/238) of cases. Fifty percent of MSM reported having passive anal sex with a male partner in the past six months and 44.1% have used Condom at the last passive anal sex. Conclusion The prevalence of CT and NG among MSM in Marrakech has increased significantly compared to the results obtained in the first study conducted in 2010, which was 6.3% for CT and 2.4% for NG. These findings confirmed the need for the establishment and the expansion of programs targeting MSM in Morocco to strengthen the prevention and control the STIs among risky groups. Disclosure No significant relationships.

The Journal of Infectious Diseases, 2019

Human papillomavirus (HPV) vaccines are indicated for anal cancer prevention, but evidence for va... more Human papillomavirus (HPV) vaccines are indicated for anal cancer prevention, but evidence for vaccine effectiveness (VE) against anal HPV infections among women is limited. We estimated the VE (≥1 dose) against anal HPV positivity of the bivalent vaccine, whose target types HPV-16/18 are associated with approximately 90% of HPV-related anal cancers. Among 548 female STI clinic visitors 16–24 years old who provided an anal swab sample as part of a repeated cross-sectional survey, VE against HPV-16/18 was 89.9% (95% confidence interval, 63.0%–97.2%). Type-specific VE correlated well with VE against cervicovaginal HPV (Spearman ρ = 0.76), suggesting comparable effectiveness of HPV-16/18 vaccination against genital and anal infections.

Viruses, 2018

Background: The most commonly found human papillomavirus (HPV) types in cervical cancer are HPV16... more Background: The most commonly found human papillomavirus (HPV) types in cervical cancer are HPV16 and HPV18. Genome variants of these types have been associated with differential carcinogenic potential. To date, only a handful of studies have described HPV18 whole genome sequencing results. Here we describe HPV18 variant diversity and conservation of persistent infections in a longitudinal retrospective cohort study. Methods: Cervical self-samples were obtained annually over four years and genotyped on the SPF10-DEIA-LiPA 25 platform. Clearing and persistent HPV18 positive infections were selected, amplified in two overlapping fragments, and sequenced using 32 sequence primers. Results: Complete viral genomes were obtained from 25 participants with persistent and 26 participants with clearing HPV18 infections, resulting in 52 unique HPV18 genomes. Sublineage A3 was predominant in this population. The consensus viral genome was completely conserved over time in persistent infections, with one exception, where different HPV18 variants were identified in follow-up samples. Conclusions: This study identified a diverse set of HPV18 variants. In persistent infections, the consensus viral genome is conserved. The identification of only one HPV18 infection with different major variants in follow-up implies that this is a potentially rare event. This dataset adds 52 HPV18 genome variants to Genbank, more than doubling the currently available HPV18 information resource, and all but one variant are unique additions.

Papillomavirus Research, 2018

Background Our objective was to identify virological and serological predictors of anal high-grad... more Background Our objective was to identify virological and serological predictors of anal high-grade squamous intraepithelial lesions (HSIL) in HIV-positive men-who-have-sex-with-men (MSM). Methods HIV-positive MSM were recruited from a longitudinal study (2010-2013), during which anal self-swabs and serum were collected at up to five biannual visits. Swabs were HPV genotyped, and type-specific HPV viral load in anal swabs was determined. Serum antibodies to E6, E7, E1, E2 and L1 proteins of 7 hrHPV-types and HPV6 and 11 were analyzed. 193 participants had a high-resolution anoscopy (HRA) after the last study visit and were included in the current analysis. Anal HSIL was diagnosed by histopathological examination of anal biopsies. Causative HPV-type of anal HSIL was determined in whole tissue sections (WTS) and by laser capture micro-dissection if more than one HPV-type was found in WTS. Multivariable logistic regression was used to study whether persistent anal HPV infection, HPV viral load and seropositivity for HPV were predictors of anal HSIL, in general and for concordant causative HPV-type. Results Of 193 HIV-positive MSM, 50 (26%) were diagnosed with anal HSIL. HrHPV persistence in anal swabs was common, varying by hrHPV-type between 3-21%. Neither anal hrHPV viral load, nor seropositivity for L1, E6, E7, E1, or E2 was associated with anal HSIL. Only anal HPV persistence was independent associated with anal HSIL, in general and by concordant causative HPV-type. Conclusion Persistent HPV infection was strongly associated with anal HSIL, in general as well as for concordant HPV-type.

The Journal of infectious diseases, Jan 4, 2018

Observational postmarketing studies are important to assess vaccine effectiveness (VE). We estima... more Observational postmarketing studies are important to assess vaccine effectiveness (VE). We estimated VE from the bivalent human papillomavirus (HPV) vaccine against HPV positivity of vaccine and nonvaccine types in a high-risk population. We included all vaccine-eligible women from the PASSYON study, a biennial cross-sectional survey in Dutch sexually transmitted infection clinics. Vaginal swabs were analyzed using a polymerase chain reaction-based assay (SPF10-LiPA25) able to detect the 12 high-risk HPV (hrHPV) types 16/18/31/33/35/39/45/51/52/56/58/59. We compared hrHPV positivity between self-reported vaccinated (≥1 dose) and unvaccinated women, and estimated VE by a logistic mixed model. We included 1087 women of which 53% were hrHPV positive and 60% reported to be vaccinated. The adjusted pooled VE against HPV-16/18 was 89.9% (81.7%-94.4%). Moreover, we calculated significant VE against nonvaccine types HPV-45 (91%), HPV-35 (57%), HPV-31 (50%), and HPV-52 (37%). Among women who...

Journal of Medical Virology, 2017

Does anal HPV viral load explain the difference in anal HPV persistence between HIVnegative and-p... more Does anal HPV viral load explain the difference in anal HPV persistence between HIVnegative and-positive men who have sex with men (MSM)? Methods MSM ≥18 years were recruited in Amsterdam, the Netherlands, in 2010-2011. Anal self-swabs were collected every 6 months and genotyped (SPF10-PCR-DEIA-LIPA25system). HPV16 and HPV18 load was determined with a type specific quantitative (q)PCR, and compared between HIV-negative and-positive men using ranksum test. Persistence was defined as ≥3 positive samples for the same HPV-type. Determinants of persistent HPV16/18 infection and its association with HPV16/18 load were assessed with logistic regression. Results Of 777 recruited MSM, 54 and 22 HIV negative men were HPV16 and HPV18 positive at baseline, and 64 and 39 HIV-positive MSM. The geometric mean titer (GMT) of HPV16 was 19.6 (95%CI 10.1-38.0) and of HPV18 8.6 (95%CI 2.7-27.5) DNA copies/ human cell. HPV16 and HPV18 load did not differ significantly between HIV-negative and-positive MSM (P=0.7; P=0.8, respectively). In multivariable analyses HPV16 load was an independent determinant of HPV16 persistence (OR 1.8, 95%CI 1.3-2.4). Conclusion No difference in anal HPV viral load was found between HIV-positive and HIVnegative MSM. HPV 16/18 viral load is an independent determinant of type-specific persistence.

Vaccine, May 1, 2015

In Japan, government support for human papillomavirus (HPV) vaccination began in November 2010. H... more In Japan, government support for human papillomavirus (HPV) vaccination began in November 2010. However, the mass media repeatedly reported on severe adverse events. The Japanese Ministry of Health, Labor and Welfare suspended proactive recommendations for HPV vaccines in June 2013. Japan's HPV vaccination rate dropped from 70% to less than 1% in 2017. We examined cervical cancer screening results in terms of abnormal cytology, histology, and HPV vaccination status among 11,903 women aged 20 to 25 y in the fiscal year 2015. The overall rate of HPV vaccination was 26.1% (3,112/11,903). Regarding cytology, the rate of atypical squamous cells of undetermined significance (ASC-US) or worse was 3.3% (103/3,112) in women who received HPV vaccination (vaccine (+) women) and 5.6% (496/8,791) in women who did not (vaccine (-) women). The rate of highgrade squamous intraepithelial lesion (HSIL) or worse was 0.26% (8/3,112) in vaccine (+) women and 0.81% (72/8,791) in vaccine (-) women. Regarding histology, the rate of cervical intraepithelial neoplasia 1 or worse (CIN1+) was 1.4% (42/3,112) in vaccine (+) women and 2.1% (178/8,791) in vaccine (-) women. The rates of CIN2+ and CIN3+ were similar regardless of vaccination. We found a significantly lower incidence of CIN in vaccine (+) women. These results suggest that the resumption of recommending HPV vaccination as primary prevention for cervical cancer is needed in Japan.

Vaccine, Apr 1, 2020

Introduction: In 2009, girls-only HPV16/18 vaccination was introduced in the Netherlands which ha... more Introduction: In 2009, girls-only HPV16/18 vaccination was introduced in the Netherlands which has achieved 46-61% uptake. Heterosexual men have benefitted from herd protection, but it is unknown whether men who have sex with men (MSM) also benefit from herd effects of the girls-only HPV16/18 vaccination program. Because MSM bear a high HPV-related disease burden, countries might consider targeted vaccination for MSM. To study possible herd effects and prior HPV exposure at a potential moment of vaccination, we assessed trends in the HPV prevalence and proportions (sero)negative for the various vaccine types among young MSM visiting sexual health centers (SHCs). Methods: We used data from MSM included in PASSYON study years 2009-2017. In this biennial crosssectional study among visitors of SHCs aged 16-24 years, MSM provided a penile and anal swab for HPV DNA testing (including vaccine types HPV6

The Journal of Infectious Diseases, Jan 9, 2020

The bivalent human papillomavirus (HPV) vaccine is highly effective and induces robust serologica... more The bivalent human papillomavirus (HPV) vaccine is highly effective and induces robust serological responses. Using a Dutch prospective cohort initiated in 2009, including 744 vaccinated and 294 unvaccinated girls (1993-1994) who provide a vaginal self-swab sample, serum sample, and questionnaire yearly, we report a high, persisting antibody response up to 9 years after vaccination for vaccine types HPV-16 or HPV-18. Antibodies against nonvaccine HPV types 31, 33, 45, 52, and 58 were lower but still significantly higher than in unvaccinated individuals. This was also reflected in the seroprevalence. We compared participant characteristics and antibody levels between vaccinated women with and those without HPV infections 1 year before infection (204 incident and 64 persistent infections), but we observed no consistent difference in type-specific antibody levels. Having a high-risk HPV infection was associated with sexual risk behavior and smoking 1 year before infection. Although high antibody levels are necessary for protection, our study suggests that on the individual level other factors such as HPV exposure or antibody avidity could be important.

BMC Genomics, 2008

Background: Whooping cough caused by Bordetella pertussis in humans, is re-emerging in many count... more Background: Whooping cough caused by Bordetella pertussis in humans, is re-emerging in many countries despite vaccination. Several studies have shown that significant shifts have occurred in the B. pertussis population resulting in antigenic divergence between vaccine strains and circulating strains and suggesting pathogen adaptation. In the Netherlands, the resurgence of pertussis is associated with the rise of B. pertussis strains with an altered promoter region for pertussis toxin (ptxP3). Results: We used Multi-Locus Sequence Typing (MLST), Multiple-Locus Variable Number of Tandem Repeat Analysis (MLVA) and microarray-based comparative genomic hybridization (CGH) to characterize the ptxP3 strains associated with the Dutch epidemic. For CGH analysis, we developed an oligonucleotide (70-mers) microarray consisting of 3,581 oligonucleotides representing 94% of the gene repertoire of the B. pertussis strain Tohama I. Nine different MLST profiles and 38 different MLVA types were found in the period 1993 to 2004. Forty-three Dutch clinical isolates were analyzed with CGH, 98 genes were found to be absent in at least one of the B. pertussis strains tested, these genes were clustered in 8 distinct regions of difference. Conclusion: The presented MLST, MLVA and CGH-analysis identified distinctive characteristics of ptxP3 B. pertussis strains-the most prominent of which was a genomic deletion removing about 23,000 bp. We propose a model for the emergence of ptxP3 strains.

PLOS ONE, Jun 11, 2013

Bordetella pertussis (B. pertussis) is the causative agent of whooping cough, which is a highly c... more Bordetella pertussis (B. pertussis) is the causative agent of whooping cough, which is a highly contagious disease in the human respiratory tract. Despite vaccination since the 1950s, pertussis remains the most prevalent vaccine-preventable disease in developed countries. A recent resurgence pertussis is associated with the expansion of B. pertussis strains with a novel allele for the pertussis toxin (ptx) promoter ptxP3 in place of resident ptxP1 strains. The recent expansion of ptxP3 strains suggests that these strains carry mutations that have increased their fitness. Compared to the ptxP1 strains, ptxP3 strains produce more Ptx, which results in increased virulence and immune suppression. In this study, we investigated the contribution of gene expression changes of various genes on the increased fitness of the ptxP3 strains. Using genome-wide gene expression profiling, we show that several virulence genes had higher expression levels in the ptxP3 strains compared to the ptxP1 strains. We provide the first evidence that wildtype ptxP3 strains are better colonizers in an intranasal mouse infection model. This study shows that the ptxP3 mutation and the genetic background of ptxP3 strains affect fitness by contributing to the ability to colonize in a mouse infection model. These results show that the genetic background of ptxP3 strains with a higher expression of virulence genes contribute to increased fitness.

Infection and Immunity, Jul 1, 2004

Bordetella pertussis is reemerging in several countries with a traditionally high vaccine uptake.... more Bordetella pertussis is reemerging in several countries with a traditionally high vaccine uptake. An analysis of clinical isolates revealed antigenic divergence between vaccine strains and circulating strains with respect to P.69 pertactin. Polymorphisms in P.69 pertactin are mainly limited to regions comprised of amino acid repeats, designated region 1 and region 2. Region 1 flanks the RGD motif, which is involved in adherence. Although antibodies against P.69 pertactin are implicated in protective immunity, little is known about the structure and location of its epitopes. Here we describe the identification by pepscan analysis of the locations of mainly linear epitopes recognized by human sera and mouse monoclonal antibodies (MAbs). A total of 24 epitopes were identified, and of these only 2 were recognized by both MAbs and human antibodies in serum. A number of immunodominant epitopes were identified which were recognized by 78 to 93% of the human sera tested. Blocking experiments indicated the presence of high-avidity human antibodies against conformational epitopes. Human antibodies against linear epitopes had much lower avidities, as they were unable to block MAbs. Pepscan analyses revealed several MAbs which bound to both region 1 and region 2. The two regions are separated by 289 amino acids in the primary structure, and we discuss the possibility that they form a single conformational epitope. Thus, both repeat regions may serve to deflect the immune response targeted to the functional domain of P.69 pertactin. This may explain why the variation in P.69 pertactin is so effective, despite the fact that it is limited to only two small segments of the molecule.

BMC Genomics, 2010

Background: Bordetella pertussis is the causative agent of human whooping cough (pertussis) and i... more Background: Bordetella pertussis is the causative agent of human whooping cough (pertussis) and is particularly severe in infants. Despite worldwide vaccinations, whooping cough remains a public health problem. A significant increase in the incidence of whooping cough has been observed in many countries since the 1990s. Several reasons for the re-emergence of this highly contagious disease have been suggested. A particularly intriguing possibility is based on evidence indicating that pathogen adaptation may play a role in this process. In an attempt to gain insight into the genomic make-up of B. pertussis over the last 60 years, we used an oligonucleotide DNA microarray to compare the genomic contents of a collection of 171 strains of B. pertussis isolates from different countries. Results: The CGH microarray analysis estimated the core genome of B. pertussis, to consist of 3,281 CDSs that are conserved among all B. pertussis strains, and represent 84.8% of all CDSs found in the 171 B. pertussis strains. A total of 64 regions of difference consisting of one or more contiguous CDSs were identified among the variable genes. CGH data also revealed that the genome size of B. pertussis strains is decreasing progressively over the past 60 years. Phylogenetic analysis of microarray data generated a minimum spanning tree that depicted the phylogenetic structure of the strains. B. pertussis strains with the same gene content were found in several different countries. However, geographic specificity of the B. pertussis strains was not observed. The gene content was determined to highly correlate with the ptxP-type of the strains. Conclusions: An overview of genomic contents of a large collection of isolates from different countries allowed us to derive a core genome and a phylogenetic structure of B. pertussis. Our results show that B. pertussis is a dynamic organism that continues to evolve.

PLOS ONE, Sep 19, 2007

Background. Bordetella pertussis is a Gram-negative bacterium that infects the human respiratory ... more Background. Bordetella pertussis is a Gram-negative bacterium that infects the human respiratory tract and causes pertussis or whooping cough. The disease has resurged in many countries including Finland where the whole-cell pertussis vaccine has been used for more than 50 years. Antigenic divergence has been observed between vaccine strains and clinical isolates in Finland. To better understand genome evolution in B. pertussis circulating in the immunized population, we developed an oligonucleotide-based microarray for comparative genomic analysis of Finnish strains isolated during the period of 50 years. Methodology/Principal Findings. The microarray consisted of 3,582 oligonucleotides (70-mer) and covered 94% of 3,816 ORFs of Tohama I, the strain of which the genome has been sequenced [1]. Twenty isolates from 1953 to 2004 were studied together with two Finnish vaccine strains and two international reference strains. The isolates were selected according to their characteristics, e.g. the year and place of isolation and pulsed-field gel electrophoresis profiles. Genomic DNA of the tested strains, along with reference DNA of Tohama I strain, was labelled and hybridized. The absence of genes as established with microarrays, was confirmed by PCR. Compared with the Tohama I strain, Finnish isolates lost 7 (8.6 kb) to 49 (55.3 kb) genes, clustered in one to four distinct loci. The number of lost genes increased with time, and one third of lost genes had functions related to inorganic ion transport and metabolism, or energy production and conversion. All four loci of lost genes were flanked by the insertion sequence element IS481. Conclusion/Significance. Our results showed that the progressive gene loss occurred in Finnish B. pertussis strains isolated during a period of 50 years and confirmed that B. pertussis is dynamic and is continuously evolving, suggesting that the bacterium may use gene loss as one strategy to adapt to highly immunized populations.

Journal of Clinical Microbiology, Jun 1, 2002

Despite more than 50 years of vaccination, Bordetella pertussis has remained endemic in The Nethe... more Despite more than 50 years of vaccination, Bordetella pertussis has remained endemic in The Netherlands, causing epidemic outbreaks every 3 to 5 years. Strain variation may play a role in the persistence of B. pertussis and was studied by sequencing 15 genes coding for surface proteins, including genes for all five components of acellular pertussis vaccines: pertussis toxin (Ptx), pertactin (Prn), filamentous hemagglutinin, and fimbriae (Fim2 and Fim3). A low level of allelic variation was observed, confirming a recent evolutionary origin of B. pertussis. In modern isolates, polymorphism was observed only in prn, ptxS1, ptxS3, and tcfA. Polymorphism in ptxS1, ptxS3, and tcfA was used to categorize isolates in multilocus sequence types (MLSTs). Analysis of Dutch isolates from 1949 to 1999 revealed five MLSTs, which showed a highly dynamic temporal behavior. We observed significant changes in the MLSTs after the introduction of pertussis vaccination in The Netherlands. Epidemic years were found to be associated with the expansion of MLST-4 or MLST-5. MLST-5 showed a remarkable expansion from 10% in 1997 to 80% in 1999. The MLST analysis was extended to a number of widely separated geographic regions: Finland, Italy, Japan, and the United States. MLST-4 and MLST-5 were found to dominate in Italy and the United States. In Finland and Japan, MLST-3 and MLST-2, respectively, were predominant. Thus, although each region showed distinctive MLST frequencies, in three of the five regions MLST-4 and MLST-5 were predominant. These types may represent newly emerged, successful clones. The identification of highly successful clones may shed light on the question of how B. pertussis is able to maintain itself in vaccinated populations.

Journal of Clinical Microbiology, 2020

Human papillomavirus (HPV) epidemiological and vaccine studies require highly sensitive HPV detec... more Human papillomavirus (HPV) epidemiological and vaccine studies require highly sensitive HPV detection systems. The widely used broad-spectrum SPF 10 -DEIA-LiPA 25 (SPF 10 method) has reduced sensitivity toward HPV-45 and -59. Therefore, anogenital samples from the PASSYON study were retrospectively analyzed with type-specific (TS) HPV-45 and -59 real-time quantitative PCR (qPCR) assays. The SPF 10 method missed 51.1% of HPV-45 and 76.1% of HPV-59 infections that were detected by the TS qPCR assays.

Clinical Infectious Diseases, 2020

Background Human papillomavirus (HPV) vaccination programs achieve substantial population-level i... more Background Human papillomavirus (HPV) vaccination programs achieve substantial population-level impact, with effects extending beyond protection of vaccinated individuals. We assessed trends in HPV prevalence up to 8 years postvaccination among men and women in the Netherlands, where bivalent HPV vaccination, targeting HPV types 16/18, has been offered to (pre)adolescent girls since 2009 with moderate vaccination coverage. Methods We used data from the PASSYON study, a survey initiated in 2009 (prevaccination) and repeated biennially among 16- to 24-year-old visitors of sexual health centers. We studied genital HPV positivity from 2009 to 2017 among women, heterosexual men, and unvaccinated women using Poisson generalized estimating equation models, adjusted for individual- and population-level confounders. Trends were studied for 25 HPV types detected by the SPF10-LiPA25 platform. Results A total of 6354 women (64.7% self-reported unvaccinated) and 2414 heterosexual men were includ...

Under the National Immunisation Programme (NIP), 1,520,301 children and pregnant women were vacci... more Under the National Immunisation Programme (NIP), 1,520,301 children and pregnant women were vaccinated in the Netherlands in 2019. Together, they received a total of 2,929,264 vaccinations. National immunisation coverage rose slightly for the first time in five years. In 2019, there were no notifications for diphtheria, tetanus, rubella, and polio. As in previous years, the number of notifications was low for Haemophilus influenzae type b (Hib; 39). The number of measles notifications was relatively high (84). The number of mumps cases (131) was double the number reported in the previous year. The number of notifications of hepatitis B (1205) remained stable. The number of notifications of meningococcal W disease (62) decreased after introduction of MenACWY-vaccination into the NIP (for 14-month-olds and 14-year-olds). This ended the rise in notifications from 2015 to 2018 (from 9 to 103). The number of pertussis notifications (6383) increased compared with 2018. Since the end of 20...

Sexually Transmitted Infections, 2013

Oral sessions Results Seropositivity for any of the 15 HPV types was 65.7%, any of the 11 hr-HPV ... more Oral sessions Results Seropositivity for any of the 15 HPV types was 65.7%, any of the 11 hr-HPV types 59.2%, and any of the four lr-HPV types 33.1%. Antibodies against multiple HPV types were more common (45.3%) than against single HPV types (20.4%). Antibodies against at least one of the four vaccine HPV types (HPV 6, 11, 16, and 18) were detected in 40.8% women. Among hr-HPV types seropositivity was the highest for HPV 16 (25.2%) and among lr-HPV types for HPV 6 (19.1%). Age-specific seropositivity for HPV 16 was the highest among 30-39 years old women (29.6%) and decreased with increasing age to 14.0% among 60-64 years old women (p = 0.014). Seropositivity for any of the hr-HPV among women with pathological cytology was 76.8% and those negative for intraepithelial lesion or malignancy 58.3% (p < 0.001). Conclusion Our results show a substantial burden of lifetime sexual exposure to these 15 HPV types before the introduction of vaccination and also a relatively high cumulative exposure to at least one of the four vaccine HPV types. Thus, vaccination of females before sexual debut with a quadrivalent HPV vaccine has a potential to contribute to a substantial reduction of the burden of cervical infections and cervical cancer as well as some other HPV related morbidity, including genital warts. Our data also present the baseline for monitoring HPV long-term vaccination impact.

Poster Presentations, 2019

Results 28 interviews were conducted (15 MSMO, 13 MSMW). Half of MSMW reported predominantly male... more Results 28 interviews were conducted (15 MSMO, 13 MSMW). Half of MSMW reported predominantly male partners and half predominantly female. MSMO viewed STIs as "an annoying reality of life" and both groups had positive perceptions of STI testing; however, MSMW described more STI stigma and less frequent testing. MSMO and MSMW who were more involved with the queer community had better sexual health knowledge. Many MSMW noted it was easier to have sexual health discussions with male partners; however, many also described the pressure of condom use, "with men, [was] to not use a condom a fair bit of time and probably by women, [was] to use a condom." There was significant fear in both groups about disclosing sexual practices to general practitioners and some MSMW preferred the anonymity of specialist sexual health clinics. Biphobia and bisexual erasure were frequently discussed by both groups. Conclusion MSMW described less comprehensive sexual health knowledge and more barriers to accessing sexual health care. Service provision and health promotion messaging must be broadened to capture the reality of increasing sexual fluidity. Destigmatising MSM behaviour and sexual health discussions, particularly in primary care, is crucial to ensuring all people receive appropriate sexual health care. Disclosure No significant relationships.

Poster Presentations, 2019

Background Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most common pathogen... more Background Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most common pathogens causing genital tract infections. They cause a significant global morbidity and mortality and have been associated with increased risk of HIV transmission, mainly among key populations fueling STIs and HIV. Men who have sex with men (MSM) had been classified by the Moroccan National AIDS Program (NAP) as a vulnerable risky group with higher burden of STIs. The aim of the present study is to assess the prevalence of CT and NG among MSM in Marrakech. Methods From October to December 2017, a total of 238 MSM were enrolled in the study using Respondent-Driven Sampling (RDS). Access to this population was facilitated by an NGO evolving in the field of HIV and STIs, with extensive experience with hard-to-reach population. Eligible recruits were aged of 18 years and older and having lived in Marrakech for the previous six months. Socio-demographic and behavioral factors were collected using a structured questionnaire. CT and NG investigations were performed using the molecular test the Xpert CT/NG tests (Cepheid, USA) on anal swab samples. Results The findings showed a prevalence of CT and NG of 9.24% (22/238) and 8.40 (20/238) respectively. A CT/NG coinfection was found in 3.36% (8/238) of cases. Fifty percent of MSM reported having passive anal sex with a male partner in the past six months and 44.1% have used Condom at the last passive anal sex. Conclusion The prevalence of CT and NG among MSM in Marrakech has increased significantly compared to the results obtained in the first study conducted in 2010, which was 6.3% for CT and 2.4% for NG. These findings confirmed the need for the establishment and the expansion of programs targeting MSM in Morocco to strengthen the prevention and control the STIs among risky groups. Disclosure No significant relationships.

The Journal of Infectious Diseases, 2019

Human papillomavirus (HPV) vaccines are indicated for anal cancer prevention, but evidence for va... more Human papillomavirus (HPV) vaccines are indicated for anal cancer prevention, but evidence for vaccine effectiveness (VE) against anal HPV infections among women is limited. We estimated the VE (≥1 dose) against anal HPV positivity of the bivalent vaccine, whose target types HPV-16/18 are associated with approximately 90% of HPV-related anal cancers. Among 548 female STI clinic visitors 16–24 years old who provided an anal swab sample as part of a repeated cross-sectional survey, VE against HPV-16/18 was 89.9% (95% confidence interval, 63.0%–97.2%). Type-specific VE correlated well with VE against cervicovaginal HPV (Spearman ρ = 0.76), suggesting comparable effectiveness of HPV-16/18 vaccination against genital and anal infections.

Viruses, 2018

Background: The most commonly found human papillomavirus (HPV) types in cervical cancer are HPV16... more Background: The most commonly found human papillomavirus (HPV) types in cervical cancer are HPV16 and HPV18. Genome variants of these types have been associated with differential carcinogenic potential. To date, only a handful of studies have described HPV18 whole genome sequencing results. Here we describe HPV18 variant diversity and conservation of persistent infections in a longitudinal retrospective cohort study. Methods: Cervical self-samples were obtained annually over four years and genotyped on the SPF10-DEIA-LiPA 25 platform. Clearing and persistent HPV18 positive infections were selected, amplified in two overlapping fragments, and sequenced using 32 sequence primers. Results: Complete viral genomes were obtained from 25 participants with persistent and 26 participants with clearing HPV18 infections, resulting in 52 unique HPV18 genomes. Sublineage A3 was predominant in this population. The consensus viral genome was completely conserved over time in persistent infections, with one exception, where different HPV18 variants were identified in follow-up samples. Conclusions: This study identified a diverse set of HPV18 variants. In persistent infections, the consensus viral genome is conserved. The identification of only one HPV18 infection with different major variants in follow-up implies that this is a potentially rare event. This dataset adds 52 HPV18 genome variants to Genbank, more than doubling the currently available HPV18 information resource, and all but one variant are unique additions.

Papillomavirus Research, 2018

Background Our objective was to identify virological and serological predictors of anal high-grad... more Background Our objective was to identify virological and serological predictors of anal high-grade squamous intraepithelial lesions (HSIL) in HIV-positive men-who-have-sex-with-men (MSM). Methods HIV-positive MSM were recruited from a longitudinal study (2010-2013), during which anal self-swabs and serum were collected at up to five biannual visits. Swabs were HPV genotyped, and type-specific HPV viral load in anal swabs was determined. Serum antibodies to E6, E7, E1, E2 and L1 proteins of 7 hrHPV-types and HPV6 and 11 were analyzed. 193 participants had a high-resolution anoscopy (HRA) after the last study visit and were included in the current analysis. Anal HSIL was diagnosed by histopathological examination of anal biopsies. Causative HPV-type of anal HSIL was determined in whole tissue sections (WTS) and by laser capture micro-dissection if more than one HPV-type was found in WTS. Multivariable logistic regression was used to study whether persistent anal HPV infection, HPV viral load and seropositivity for HPV were predictors of anal HSIL, in general and for concordant causative HPV-type. Results Of 193 HIV-positive MSM, 50 (26%) were diagnosed with anal HSIL. HrHPV persistence in anal swabs was common, varying by hrHPV-type between 3-21%. Neither anal hrHPV viral load, nor seropositivity for L1, E6, E7, E1, or E2 was associated with anal HSIL. Only anal HPV persistence was independent associated with anal HSIL, in general and by concordant causative HPV-type. Conclusion Persistent HPV infection was strongly associated with anal HSIL, in general as well as for concordant HPV-type.

The Journal of infectious diseases, Jan 4, 2018

Observational postmarketing studies are important to assess vaccine effectiveness (VE). We estima... more Observational postmarketing studies are important to assess vaccine effectiveness (VE). We estimated VE from the bivalent human papillomavirus (HPV) vaccine against HPV positivity of vaccine and nonvaccine types in a high-risk population. We included all vaccine-eligible women from the PASSYON study, a biennial cross-sectional survey in Dutch sexually transmitted infection clinics. Vaginal swabs were analyzed using a polymerase chain reaction-based assay (SPF10-LiPA25) able to detect the 12 high-risk HPV (hrHPV) types 16/18/31/33/35/39/45/51/52/56/58/59. We compared hrHPV positivity between self-reported vaccinated (≥1 dose) and unvaccinated women, and estimated VE by a logistic mixed model. We included 1087 women of which 53% were hrHPV positive and 60% reported to be vaccinated. The adjusted pooled VE against HPV-16/18 was 89.9% (81.7%-94.4%). Moreover, we calculated significant VE against nonvaccine types HPV-45 (91%), HPV-35 (57%), HPV-31 (50%), and HPV-52 (37%). Among women who...

Journal of Medical Virology, 2017

Does anal HPV viral load explain the difference in anal HPV persistence between HIVnegative and-p... more Does anal HPV viral load explain the difference in anal HPV persistence between HIVnegative and-positive men who have sex with men (MSM)? Methods MSM ≥18 years were recruited in Amsterdam, the Netherlands, in 2010-2011. Anal self-swabs were collected every 6 months and genotyped (SPF10-PCR-DEIA-LIPA25system). HPV16 and HPV18 load was determined with a type specific quantitative (q)PCR, and compared between HIV-negative and-positive men using ranksum test. Persistence was defined as ≥3 positive samples for the same HPV-type. Determinants of persistent HPV16/18 infection and its association with HPV16/18 load were assessed with logistic regression. Results Of 777 recruited MSM, 54 and 22 HIV negative men were HPV16 and HPV18 positive at baseline, and 64 and 39 HIV-positive MSM. The geometric mean titer (GMT) of HPV16 was 19.6 (95%CI 10.1-38.0) and of HPV18 8.6 (95%CI 2.7-27.5) DNA copies/ human cell. HPV16 and HPV18 load did not differ significantly between HIV-negative and-positive MSM (P=0.7; P=0.8, respectively). In multivariable analyses HPV16 load was an independent determinant of HPV16 persistence (OR 1.8, 95%CI 1.3-2.4). Conclusion No difference in anal HPV viral load was found between HIV-positive and HIVnegative MSM. HPV 16/18 viral load is an independent determinant of type-specific persistence.