Chris J L M Meijer

VU University Medical Center, Amsterdamo, North Holland, Netherlands

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Publications (913)5174.87 Total impact

  • Cancer Cytopathology 09/2015; DOI:10.1002/cncy.21622 · 3.35 Impact Factor
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    ABSTRACT: Human papillomavirus (HPV)-related screening technologies and HPV vaccination offer enormous potential for cancer prevention, notably prevention of cervical cancer. The effectiveness of these approaches is, however, suboptimal owing to limited implementation of screening programmes and restricted indications for HPV vaccination. Trials of HPV vaccination in women aged up to 55 years have shown almost 90% protection from cervical precancer caused by HPV16/18 among HPV16/18-DNA-negative women. We propose extending routine vaccination programmes to women of up to 30 years of age (and to the 45-50-year age groups in some settings), paired with at least one HPV-screening test at age 30 years or older. Expanding the indications for HPV vaccination and much greater use of HPV testing in screening programmes has the potential to accelerate the decline in cervical cancer incidence. Such a combined protocol would represent an attractive approach for many health-care systems, in particular, countries in Central and Eastern Europe, Latin America, Asia, and some more-developed parts of Africa. The role of vaccination in women aged >30 years and the optimal number of HPV-screening tests required in vaccinated women remain important research issues. Cost-effectiveness models will help determine the optimal combination of HPV vaccination and screening in public health programmes, and to estimate the effects of such approaches in different populations.
    Nature Reviews Clinical Oncology 09/2015; DOI:10.1038/nrclinonc.2015.146 · 14.18 Impact Factor
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    ABSTRACT: Recently, DNA methylation analysis of FAM19A4 in cervical scrapes has been shown to adequately detect high-grade cervical intraepithelial neoplasia and cervical cancer (≥CIN3) in high-risk HPV (hrHPV)-positive women. Here, we compared the clinical performance of FAM19A4 methylation analysis to cytology and HPV16/18 genotyping, separately and in combination, for ≥CIN3 detection in hrHPV-positive women participating in a prospective observational multi-center cohort study. The study population comprised hrHPV-positive women aged 18-66 years, visiting a gynecological outpatient clinic. From these women, cervical scrapes and colposcopy-directed biopsies (for histological confirmation) were obtained. Cervical scrapes were analyzed for FAM19A4 gene promoter methylation, cytology and HPV16/18 genotyping. Methylation analysis was performed by quantitative methylation-specific PCR (qMSP). Sensitivities and specificities for ≥CIN3 were compared between tests. Stratified analyses were performed for variables that potentially influence marker performance. Of all 508 hrHPV-positive women, the sensitivities for ≥CIN3 of cytology, FAM19A4 methylation analysis, and cytology combined with HPV16/18 genotyping were 85.6%, 75.6% and 92.2%, respectively, with corresponding specificities of 49.8%, 71.1%, and 29.4%, respectively. Both sensitivity and specificity of FAM19A4 methylation analysis were associated with age (p≤0.001 each). In women ≥30 years (n=287), ≥CIN3 sensitivity of FAM19A4 methylation analysis was 88.3% (95%CI:80.2-96.5) which was non-inferior to that of cytology [85.5% (95%CI:76.0-94.0)], at a significantly higher specificity [62.1% (95%CI:55.8-68.4) compared to 47.6% (95%CI:41.1-54.1)]. In conclusion, among hrHPV-positive women from an outpatient population aged ≥30 years, methylation analysis of FAM19A4 is an attractive marker for the identification of women with ≥CIN3. This article is protected by copyright. All rights reserved. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 08/2015; DOI:10.1002/ijc.29824 · 5.09 Impact Factor
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    ABSTRACT: Recent studies have shown that CADM1/MAL methylation levels in cervical scrapes increase with severity and duration of the underlying cervical intraepithelial neoplasia (CIN) lesion. Multiple lesions of different histological grades and duration are frequently present on the cervix. To gain more insight into the possible epigenetic heterogeneity and its consequences for the methylation status in cervical scrapes, we performed an exploratory study of CADM1/MAL methylation in different grades of CIN lesions present in women with multiple cervical biopsies. CADM1-M18 and MAL-M1 methylation was assessed using a standardised, multiplex, quantitative methylation specific PCR on 178 biopsies with various grades of CIN in 65 women, and in their corresponding cervical scrapes. CADM1/MAL methylation positivity increased with disease severity, from 5.5% in normal biopsies to 63.3% and 100% in biopsies with CIN3 and cervical cancer, respectively. In the majority (8/9) of women where besides a CIN2/3 lesion a biopsy from normal cervical tissue was present, the CIN2/3 biopsy was CADM1/MAL methylation positive and the normal biopsy was CADM1/MAL methylation negative. A good concordance (78%) was found between CADM1/MAL methylation results on the scrapes and the biopsy with the worst diagnosis, particularly between samples of women with CIN3 and cervical cancer (92% and 100% concordance, respectively). Thus, in women with multiple cervical biopsies, CADM1/MAL methylation increases with severity of the lesion and is lesion-specific. CADM1/MAL methylation status in cervical scrapes appears to be representative of the worst underlying lesion, particularly for CIN3 and cervical cancer.
    International Journal of Cancer 08/2015; DOI:10.1002/ijc.29706 · 5.09 Impact Factor
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    ABSTRACT: To study the source of human papillomavirus (HPV) in semen. Observational study (CCMO-NL3248800010). Academic hospital-based laboratory. Healthy male volunteers (n = 213). One penile scrape and three semen samples per participant for HPV-DNA testing by both GP5+/6+ polymerase chain reaction (PCR) and SPF10 PCR to detect moderate/high and low viral loads, respectively; flat penile lesions (FPL) detected by penoscopy. HPV-DNA presence in semen and penile scrapes, and the presence of FPL. HPV-DNA at moderate/high viral loads (i.e., GP5+/6+ PCR positive) was detected in ≥1 semen sample(s) in 27% of participants. Most men with moderate/high viral loads in the penile scrape also had moderate/high viral loads in semen (85%). Men with a HPV-negative penile scrape were very unlikely to have moderate/high viral loads in semen (3%). The presence of HPV in semen was associated with the presence of HPV in the penile scrape also on a genotype-specific level. Having FPL was a risk factor for HPV presence in semen. HPV-DNA presence in semen of healthy men is common and associated with HPV infections of the penile epithelium. HPV-DNA presence in semen may result from desquamation of HPV-infected penile cells. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
    Fertility and sterility 07/2015; DOI:10.1016/j.fertnstert.2015.06.028 · 4.59 Impact Factor
  • JAIDS Journal of Acquired Immune Deficiency Syndromes 06/2015; DOI:10.1097/QAI.0000000000000744 · 4.56 Impact Factor
  • Paolo Giorgi-Rossi · Marc Arbyn · Chris J L M Meijer
    JAMA Internal Medicine 06/2015; 175(6):1068. DOI:10.1001/jamainternmed.2015.0592 · 13.12 Impact Factor
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    ABSTRACT: Primary human papillomavirus (HPV)-based screening results in a 2-5% lower specificity for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) compared to Pap cytology. To identify HPV-positive women with CIN2+, we retrospectively evaluated the cross-sectional and longitudinal performance of p16/Ki-67 dual-stained cytology in HPV-positive women with normal cytology participating in population-based cervical screening.Conventional Pap cytology specimens of 847 of these women derived from the VUSA-Screen study were dual-stained for p16/Ki-67. Cross-sectional clinical performance in detecting CIN3 or worse (CIN3+), and CIN2+ was compared to that of baseline HPV genotyping. Moreover, 5-year cumulative incidence risks (CIR) for CIN3+ (CIN2+) were determined.The sensitivity of p16/Ki-67 dual-stained cytology for CIN3+ (CIN2+) was 73.3% (68.8%) with a specificity of 70.0% (72.8%). HPV16/18 genotyping showed a sensitivity for CIN3+ (CIN2+) of 46.7% (43.8%), with a specificity of 78.3% (79.4%). The 5-year CIR for CIN3+ in HPV-positive women with normal cytology was 6.9%. Testing these women with p16/Ki-67 dual-stained cytology resulted in a significantly lower CIN3+ 5-year CIR of 3.3% (p=0.017) in case of a negative test result. A negative HPV16/18 genotyping test result also led to a lower 5-year CIN3+ CIR of 3.6%.p16/Ki-67 dual-stained cytology detects more than 70% of underlying CIN3+ lesions in HPV-positive women with normal cytology at baseline and is therefore suitable for triaging these women to colposcopy. Furthermore, the CIN3+ 5-year CIR of 3.3% after a negative dual-stain result is significantly lower compared to the 5-year CIR of 6.9% in women without p16/Ki-67 dual-stained cytology triage. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 05/2015; 136(10). DOI:10.1002/ijc.29290 · 5.09 Impact Factor
  • Haematologica 05/2015; 100(9). DOI:10.3324/haematol.2014.118828 · 5.81 Impact Factor
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    ABSTRACT: Objective: To assess the reduction in the vaccine preventable burden of cancer in men if boys are vaccinated along with girls against oncogenic human papillomavirus (HPV). Design: Bayesian evidence synthesis approach used to evaluate the impact of vaccination against HPV types 16 and 18 on the burden of anal, penile, and oropharyngeal carcinomas among heterosexual men and men who have sex with men. The reduced transmission of vaccine-type HPV from vaccination of girls was assumed to lower the risk of HPV associated cancer in all men but not to affect the excess risk of HPV associated cancers among men who have sex with men. Setting: General population in the Netherlands. Intervention: Inclusion of boys aged 12 into HPV vaccination programmes. Main outcom e measures:Quality adjusted life years (QALYs) and numbers needed to vaccinate. Results:Before HPV vaccination, 14.9 (95% credible interval 12.2 to 18.1) QALYs per thousand men were lost to vaccine preventable cancers associated with HPV in the Netherlands. This burden would be reduced by 37% (28% to 48%) if the vaccine uptake among girls remains at the current level of 60%. To prevent one additional case of cancer among men, 795 boys (660 to 987) would need to be vaccinated; with tumour specific numbers for anal, penile, and oropharyngeal cancer of 2162, 3486, and 1975, respectively. The burden of HPV related cancer in men would be reduced by 66% (53% to 805) if vaccine uptake among girls increases to 90%. In that case, 1735 boys (1240 to 2900) would need to be vaccinated to prevent an additional case; with tumour specific numbers for anal, penile, and oropharyngeal cancer of 2593, 29107, and 6484, respectively. Conclusions: Men will benefit indirectly from vaccination of girls but remain at risk of cancers associated with HPV. The incremental benefit of vaccinating boys when vaccine uptake among girls is high is driven by the prevention of anal carcinomas, which underscores the relevance of HPV prevention efforts for men who have sex with men.
    BMJ (online) 05/2015; 350(may12 7):h2016-h2016. DOI:10.1136/bmj.h2016 · 17.45 Impact Factor
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    ABSTRACT: Several countries are in the process of switching to hrHPV (high-risk human papillomavirus) testing for cervical cancer screening. Given the multitude of available tests, validated assays which assure high-quality screening need to be identified. A systematic review was conducted to answer the question which hrHPV tests fulfill the criteria defined by an international expert team in 2009, based on reproducibility and relative sensitivity and specificity compared to Hybrid Capture-2 or GP5+/6+ PCR-EIA. These hrHPV DNA assays were validated in large randomized trials and cohorts with follow-up of eight years or more. Eligible studies citing the 2009-guideline were retrieved from and from a meta-analysis assessing the relative accuracy of new hrHPV assays versus the standard comparator tests to detect high-grade cervical intraepithelial neoplasia or cancer in primary screening. The cobas 4800 HPV Test and RealTime High Risk HPV test were consistently validated in two and three studies, respectively, whereas PapilloCheck HPV-screening test, BD Onclarity HPV assay and the HPV Risk Assay were validated each in one study. Other tests which partially fulfil the 2009-guidelines are: Cervista HPV HR Test, PCR-LMNX, a homebrew E6/E7 RT qPCR and MALDI-TOF. The APTIMA HPV assay targeting E6/E7 mRNA of hrHPV was also fully validated. However, the cross-sectional equivalency criteria of the 2009-guidelines were set up for HPV DNA assays. Demonstration of a low risk of CIN3+ after a negative APTIMA test over a longer period is waited for to inform about its utility in cervical cancer screening at five year or longer intervals. Copyright © 2015. Published by Elsevier Ltd.
    Clinical Microbiology and Infection 05/2015; DOI:10.1016/j.cmi.2015.04.015 · 5.77 Impact Factor
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    ABSTRACT: High-risk human papillomavirus (hrHPV) DNA positive women require triage testing to identify those with high-grade cervical intraepithelial neoplasia or cancer (≥CIN2). Comparing three triage algorithms (1) E7 mRNA testing following HPV16/18/31/33/45/52/58 genotyping (E7 mRNA test), (2) HPV16/18 DNA genotyping and (3) cytology, for ≥CIN2 detection in hrHPV DNA-positive women. hrHPV DNA-positive women aged 18-63 years visiting gynecology outpatient clinics were included in a prospective observational cohort study. From these women a cervical scrape and colposcopy-directed biopsies were obtained. Cervical scrapes were evaluated by cytology, HPV DNA genotyping by bead-based multiplex genotyping of GP5+6+-PCR-products, and presence of HPV16/18/31/33/45/52/58 E7 mRNA using nucleic acid sequence-based amplification (NASBA) in DNA positive women for respective HPV types. Sensitivities and specificities for ≥CIN2 were compared between E7 mRNA test and HPV16/18 DNA genotyping in the total group (n=348), and E7 mRNA test and cytology in a subgroup of women referred for non-cervix-related gynecological complaints (n=133). Sensitivity for ≥CIN2 of the E7 mRNA test was slightly higher than that of HPV16/18 DNA genotyping (66.9% versus 60.9%; ratio 1.10, 95% CI: 1.0002-1.21), at similar specificity (54.8% versus 52.3%; ratio 1.05, 95% CI: 0.93-1.18). Neither sensitivity nor specificity of the E7 mRNA test differed significantly from that of cytology (sensitivity: 68.8% versus 75.0%; ratio 0.92, 95% CI: 0.72-1.17; specificity: 59.4% versus 65.3%; ratio 0.91, 95% CI: 0.75-1.10). For detection of ≥CIN2 in hrHPV DNA-positive women, an algorithm including E7 mRNA testing following HPV16/18/31/33/45/52/58 DNA genotyping performs similar to HPV16/18 DNA genotyping or cytology. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of Clinical Virology 04/2015; 67. DOI:10.1016/j.jcv.2015.04.004 · 3.02 Impact Factor
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    ABSTRACT: Introduction: Because of the long interval between infection with high-risk human papillomavirus (hrHPV) and development of cervical cancer surrogate markers for cancer incidence are necessary to monitor vaccine effectiveness (VE). The aim of this study was to calculate VE of HPV16/18 vaccination by annually assessing incident and persistent infections among (un)vaccinated girls from the general Dutch population up to 3 years after vaccination. Methods: In 2009, 1668 girls (54% vaccinated) aged 14-16 years were enrolled in a prospective cohort study. Annually, questionnaire data were obtained, and a vaginal swab was tested for type-specific HPV DNA with SPF10-LiPA. VE was estimated by a Poisson model comparing type-specific infection rates in (un)vaccinated girls. Results: The adjusted VE (95% CI) was 73% (49-86%) against incident infections with HPV16/18 and 72% (52-84%) against HPV16/18/31/45. VE against persistent HPV16/18 was 100% and 76% (-17 to 95%) against HPV16/18/31/45. This number was lower (36%) when girls who were positive for HPV16 and 18 at baseline were included in the analysis. The overall VE for hrHPV types combined was small. Although 96% of girls were HPV-naïve at baseline, the cumulative 36-month incidence for any HPV was 20%, indicating high sexual activity. Discussion: Vaccination is effective against incident and persistent infections with HPV16/18 and HPV16/18/31/45. Low VE against persistent HPV16/18 infection in girls positive at baseline indicates importance of vaccination before sexual debut.
    Vaccine 04/2015; 33(23). DOI:10.1016/j.vaccine.2015.04.016 · 3.62 Impact Factor
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    ABSTRACT: Enteropathy-Associated T-cell Lymphoma (EATL) is a rare intestinal non-Hodgkin lymphoma with a poor, though variable prognosis. The International Prognostic Index (IPI) and the prognostic index for peripheral T-cell lymphoma (PIT) have limited predictive value for outcome of EATL. The purpose of this study was to develop and validate a prognostic model for EATL, which can identify high risk patients who need more aggressive therapy. This retrospective multicenter study was based on 92 patients and included 45 patients diagnosed with EATL between 1999 and 2009 from the Netherlands and 47 patients from England and Scotland, diagnosed with EATL between 1994 and 1998. A new EATL prognostic index (EPI) was constructed using the RPART (recursive partitioning and regression trees) procedure. Validation was performed applying the bootstrap method. Three risk groups were distinguished (P<0.0001): a high risk group, characterized by the presence of B-symptoms (median overall survival (OS) of 2 months); an intermediate risk group, comprising patients without B-symptoms and an IPI score ≥ 2 (7 months); and a low risk group, representing patients without B-symptoms and an IPI score of 0-1 (34 months). Internal validation showed stability of statistical significance and prognostic discrimination. In contrast to the IPI and PIT, the EPI better classified patients in risk groups according to their clinical outcome. Our new validated prognostic model EPI accurately predicts survival outcome in EATL and may be used for patient selection for new therapeutic strategies and evaluation of clinical trials. Copyright © 2015, American Association for Cancer Research.
    Clinical Cancer Research 03/2015; 21(13). DOI:10.1158/1078-0432.CCR-14-2195 · 8.72 Impact Factor
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    ABSTRACT: Primary human papillomavirus (HPV)-based cervical screening will be introduced in The Netherlands in 2016. We assessed the five-year cervical (pre)cancer risk of women with different combinations of HPV- and cytology test results. Special attention was paid to risks for cervical intraepithelial neoplasia grade 3 and 2 or more (CIN3+/2+) of HPV-positive women with a negative triage-test, since this determines the safety of a five year screenings interval for HPV-positive, triage test negative women. In addition, age-related effects were studied. 25,553 women were screened by HPV-testing and cytology in a screening-setting. Women were managed on presence of HPV and/or abnormal cytology. Five-year cumulative incidences for CIN3+/2+ were calculated. Five-year CIN3+(2+) risk was 10.0%(17.7%) among HPV-positive women. When stratified by cytology, the CIN3+(CIN2+) risk was 7.9%(12.9%) for women with normal cytology and 22.2%(45.3%) for women with equivocal or mildly abnormal (i.e. BMD) cytology. For HPV-negative women the five-year CIN3+(2+) risk was 0.09%(0.21%). Additional triage of HPV-positive women with normal cytology by repeat-cytology at 12 months showed a five-year CIN3+(2+) risk of 4.1%(7.0%). HPV-non16/18-positive women with normal cytology at baseline had comparable risks of 3.5%(7.9%). HPV-non 16/18-positive women with normal baseline cytology and normal repeat-cytology had a five-year CIN3+ risk of 0.42%. No age-related effects were detected. In conclusion, HPV-positive women with normal cytology and a negative triage test, either repeat-cytology after 12 months or baseline HPV 16/18 genotyping, develop a non-negligible CIN3+ risk over five years. Therefore, extension of the screening interval over five years only seems possible for HPV-screen negative women. Copyright © 2015, American Association for Cancer Research.
    Cancer Prevention Research 03/2015; 8(6). DOI:10.1158/1940-6207.CAPR-14-0409 · 4.44 Impact Factor
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    ABSTRACT: The European Medicines Agency (EMA) recently approved two-dose immunization schedules for bivalent (HPV 16/18) and quadrivalent (HPV 6/11/16/18) human papillomavirus (HPV) vaccines in nine to fourteen and thirteen year-old-girls, respectively. Registration was based on trials comparing immunogenicity of two-dose schedules in girls 9-14 years to three-dose schedules in young women 15-26 years. We evaluate comparability of antibody levels between and within age groups and discuss potential implications for monitoring the effectiveness of HPV vaccination. A systematic literature search was performed for studies comparing immunogenicity of two-to three-dose schedules of HPV vaccination. We compared geometric mean concentrations (GMCs) of vaccine-type antibodies between different dosing schedules across different age groups. Meta-analysis was used to estimate pooled GMC ratios (bivalent vaccine) of two-compared with three--dose schedules within girls. For both vaccines, two-dose immunization of girls yielded non-inferior GMCs relative to a three-dose schedule in young women up to respectively 36 and 48 months follow-up. Pooled GMC ratios for the bivalent vaccine within girls showed the two-dose schedule becoming inferior to the three-dose schedule in girls for HPV 16 at approximately two years after the first dose. For the quadrivalent vaccine, antibody responses for HPV-18 became inferior from 18 months follow-up onwards when comparing the two-dose schedule three-dose with the two-dose schedule within in girls. Two-dose immunization of girls has non-inferior immunogenicity compared to a three-dose schedule among young women. However, non-inferior immunogenicity of two-compared with three-dose schedules within girls has not been shown at all time points. Due to this inconclusive evidence, implementation of two-dose HPV vaccination needs to be monitored closely. Copyright © 2015. Published by Elsevier Ltd.
    Journal of Infection 02/2015; 71(1). DOI:10.1016/j.jinf.2015.02.005 · 4.44 Impact Factor
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    ABSTRACT: Triage of HPV screen-positive women is needed to identify those with underlying cervical intraepithelial neoplasia grade 2/3 or worse (CIN2/3+). Presently, cytology on a physician-taken cervical scrape is mostly accepted as triage test, but needs follow-up testing in order not to miss severe disease. Here, we evaluated the performance of combined cytology and bi-marker CADM1/MAL-methylation analysis as triage test on physician-taken cervical scrapes of HPV positive women. In this post-hoc analysis, we used 364 left-over HPV positive cytology triage samples of participants of a randomized controlled trial (PROHTECT-3: n=46,001) performed in population-based cervical screening. Study endpoints were CIN2+ and CIN3+ detection. Cytology testing with and without methylation marker analysis was evaluated with regard to sensitivity, specificity, positive and negative predictive value, and referral rate. Bi-marker CADM1/MAL-methylation positivity increased proportionally with severity of underlying lesions. Overall, cytology and bi-marker CADM1/MAL-methylation analysis yielded similar performances with regard to CIN3+ detection, yet in combination a significantly higher sensitivity for CIN3+ (88.7%) was obtained at a specificity of 53.6% and a colposcopy referral rate of 53.6%. The combined strategy detected all six cervical cancers, whereas triage by cytology alone failed to detect two of them. Cytology and bi-marker CADM1/MAL-methylation analysis perform complementary for CIN2+/CIN3+ detection when used as triage tool on cervical scrapes of HPV positive women. This approach not only results in a higher CIN3+ sensitivity than cytology triage with an acceptable referral rate, but also seems to reduce the risk of missing cervical cancers and advanced high-grade lesions. Copyright © 2015. Published by Elsevier Inc.
    Gynecologic Oncology 02/2015; 137(1). DOI:10.1016/j.ygyno.2015.01.550 · 3.77 Impact Factor
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    ABSTRACT: Abstract High-risk human papillomavirus (hrHPV)-induced immortalization and malignant transformation are accompanied by DNA methylation of host genes. To determine when methylation is established during cell immortalization and whether it is hrHPV-type dependent, DNA methylation was studied in a large panel of HPVE6E7-immortalized keratinocyte cell lines. These cell lines displayed different growth behaviors, i.e., continuous growth versus crisis period prior to immortalization, reflecting differential immortalization capacities of the seven HPV-types (16/18/31/33/45/66/70) studied. In this study, cells were monitored for hypermethylation of 14 host genes (APC, CADM1, CYGB, FAM19A4, hTERT, miR124-1, miR124-2, miR124-3, MAL, PHACTR3, PRDM14, RASSF1A, ROBO3, and SFRP2) at 4 different stages during immortalization. A significant increase in overall methylation levels was seen with progression through each stage of immortalization. At stage 1 (pre-immortalization), a significant increase in methylation of hTERT, miR124-2, and PRDM14 was already apparent, which continued over time. Methylation of ROBO3 was significantly increased at stage 2 (early immortal), followed by CYGB (stage 3) and FAM19A4, MAL, PHACTR3, and SFRP2 (stage 4). Methylation patterns were mostly growth behavior independent. Yet, hTERT methylation levels were significantly increased in cells that just escaped from crisis. Bisulfite sequencing of hTERT confirmed increased methylation in immortal cells compared to controls, with the transcription core and known repressor sites remaining largely unmethylated. In conclusion, HPV-induced immortalization is associated with a sequential and progressive increase in promoter methylation of a subset of genes, which is mostly independent of the viral immortalization capacity.
    Epigenetics: official journal of the DNA Methylation Society 01/2015; 10(1). DOI:10.4161/15592294.2014.990787 · 4.78 Impact Factor
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    ABSTRACT: Background Our aim was to compare the 12-month incidence and clearance of oral high-risk HPV infection between HIV-infected men who have sex with men (MSM) and HIV-negative MSM.MethodsMSM aged 18 years or older were recruited in Amsterdam, the Netherlands. Questionnaire data and oral-rinse and gargle samples were collected at baseline, and after 6 and 12 months. HPV DNA was genotyped using the SPF10-PCR & DEIA-LiPA25 system (version 1). Determinants of oral HPV incidence and clearance were explored using Cox and logistic regression analyses respectively.Results433 HIV-negative and 290 HIV-infected MSM were included in these analyses. The median follow-up time per participant was 12 months (range 3¿15). During follow-up, 114 incident oral high-risk HPV infections were observed. The incidence rate of HPV-16 was 3.5/1000 person-months (PM) in HIV-infected and 0.9/1000 PM in HIV-negative MSM (IRR 4.1; 95%CI 1.3-13.2). The incidence rates of other high-risk HPV types ranged between 1.3-3.5/1000 PM in HIV-infected and 0.0-1.1/1000 PM in HIV-negative MSM. In multivariable analyses, HIV infection (adjusted hazard ratio [aHR] 3.8; 95%CI 2.3-6.2) and a higher number of recent oral sex partners (aHR 2.4 for ¿8 partners compared to ¿2; 95%CI 1.4-4.2) were associated with HPV incidence. Of the 111 baseline oral high-risk infections, 59 (53.2%) were cleared. In multivariable analyses, only a higher number of recent oral sex partners was associated with HPV clearance (adjusted odds ratio 3.4 for ¿8 compared to ¿2 partners; 95%CI 1.3-9.0).Conclusions The incidence rate of oral high-risk HPV infection was higher in HIV-infected MSM and in those with a higher number of recent oral sex partners. Just over half of the oral high-risk HPV infections at baseline were cleared after 12 months, with a higher likelihood of clearance among MSM reporting higher numbers of recent oral sex partners, but no difference by HIV status.
    BMC Infectious Diseases 12/2014; 14(1):3845. DOI:10.1186/s12879-014-0668-z · 2.61 Impact Factor
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    ABSTRACT: Cytological screening has substantially decreased the cervical cancer incidence, but even better protection may be achieved by primary high-risk human papillomavirus (hrHPV) screening. In the Netherlands, five-yearly cytological screening for women aged 30-60 years will be replaced by primary hrHPV screening in 2016. The new screening guidelines involve an extension of the screening interval from 5 to 10 years for hrHPV-negative women aged 40 or 50 years. We investigated the impact of this program change on the lifetime cancer risks in women without an hrHPV infection at age 30, 35, 40, 45, or 50 years. The time to cancer was estimated using 14-year follow-up data from a population-based screening intervention trial and the nationwide database of histopathology reports. The new screening guidelines are expected to lead to a reduced cervical cancer risk for all age groups. The average risk reduction was 34% and was smallest (25%) among women aged 35 years. The impact of hrHPV screening on the cancer risk was sensitive to the duration from cervical intraepithelial neoplasia grade 2/3 (CIN2/3) to cancer; a small increase in the cancer risk was estimated for women aged 35 or 40 years in case a substantial proportion of CIN2/3 showed fast progression to cancer. Our results indicate that primary hrHPV screening with a 10-yearly interval for hrHPV-negative women of age 40 and beyond will lead to a further reduction in lifetime cancer risk compared to 5-yearly cytology, provided that precancerous lesions progress slowly to cancer. This article is protected by copyright. All rights reserved. Copyright © 2014 UICC.
    International Journal of Cancer 12/2014; 137(2). DOI:10.1002/ijc.29381 · 5.09 Impact Factor

Publication Stats

56k Citations
5,174.87 Total Impact Points


  • 2001–2015
    • VU University Medical Center
      • Department of Pathology
      Amsterdamo, North Holland, Netherlands
    • Vanderbilt University
      Nashville, Michigan, United States
    • Instituto Nacional de Salud Pública
      • The Center for Population Health Research
      Cuernavaca, Morelos, Mexico
  • 1985–2015
    • VU University Amsterdam
      • Department of Pathology
      Amsterdamo, North Holland, Netherlands
  • 2013
    • National Institute for Public Health and the Environment (RIVM)
      • Laboratory for Infectious Diseases and Perinatal Screening
      Utrecht, Provincie Utrecht, Netherlands
  • 1976–2012
    • University of Amsterdam
      • • Department of Pathology
      • • Department of Obstetrics and Gynaecology
      • • Department of Dermatology
      Amsterdamo, North Holland, Netherlands
  • 1970–2012
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Department of Pathology
      • • Department of Radiology
      Amsterdamo, North Holland, Netherlands
  • 2008
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands
    • University Medical Center Utrecht
      • Department of Gynaecology
      Utrecht, Provincie Utrecht, Netherlands
  • 1975–2008
    • Leiden University Medical Centre
      • • Department of Dermatology
      • • Department of Pathology
      Leiden, South Holland, Netherlands
  • 2007
    • University of North Carolina at Chapel Hill
      • Department of Epidemiology
      Chapel Hill, NC, United States
  • 1996–2007
    • Netherlands Cancer Institute
      • Department of Pathology
      Amsterdam, North Holland, Netherlands
  • 2005
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany
    • Erasmus Universiteit Rotterdam
      • Department of Obstetrics and Gynaecology
      Rotterdam, South Holland, Netherlands
  • 1999–2005
    • Danish Cancer Society
      København, Capital Region, Denmark
  • 2003–2004
    • International Agency for Research on Cancer
      • Section of Cancer Information
      Lyons, Rhône-Alpes, France
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
    • University of Buenos Aires
      Buenos Aires, Buenos Aires F.D., Argentina
    • Institut Català d'Oncologia
      Barcino, Catalonia, Spain
  • 2002
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 1998
    • Philippine General Hospital
      Manila, National Capital Region, Philippines
  • 1997
    • Statens Serum Institut
      • Department of Epidemiology Research
      København, Capital Region, Denmark
  • 1994
    • University of São Paulo
      • Departamento de Medicina Preventiva (FM) (São Paulo)
      San Paulo, São Paulo, Brazil
  • 1993
    • Utrecht University
      • Department of Dermatology and Allergology
      Utrecht, Utrecht, Netherlands
  • 1991
    • The Australian Society of Otolaryngology Head & Neck Surgery
      Evans Head, New South Wales, Australia
  • 1988
    • Stanford Medicine
      • Department of Pathology
      Stanford, California, United States
  • 1980–1983
    • Leiden University
      Leyden, South Holland, Netherlands