C J Meijer

Centro di Riferimento per l'Epidemiologia e la Prevenzione Oncologica in Piemonte, Torino, Piedmont, Italy

Are you C J Meijer?

Claim your profile

Publications (999)5533.6 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Methylation marker analysis using bi-marker panel MAL/miR-124-2 is a promising triage test for identifying cervical (pre)cancer in high-risk human papillomavirus (hrHPV) positive women. Bi-marker panel MAL/miR-124-2 can be applied directly on self-sampled cervico-vaginal material and its sensitivity is non-inferior to that of cytology, yet at the cost of more colposcopy referrals. Our objective was to increase specificity of MAL/miR-124-2 methylation analysis by varying the assay thresholds and adding HPV16/18 genotyping.
    Gynecologic oncology. 08/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Primary screening for high-risk human papillomavirus (hrHPV) requires a triage protocol. Repeat cytology testing at baseline and after 6-12 months has emerged as a reasonable triage approach, but carries the risk of loss to follow-up. Repeat cytology testing may be omitted if cytology is supplemented with another, complementary triage test at baseline. In this study, the performance of combined triage by cytology and DNA methylation analysis was assessed. In hrHPV-positive cervical scrapes (n=250), cytology (threshold: atypical squamous cells of undetermined significance (ASCUS)), bi-marker CADM1/MAL methylation testing (at different assay thresholds) and combinations of both, were evaluated for endpoints cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+). At a predefined methylation threshold of 70% specificity for CIN3+, combined triage revealed a CIN3+ sensitivity of 86.8% (95% CI: 76.1-97.6) compared to 65.8% (95% CI: 50.7-80.9) for sole cytology triage testing. Corresponding CIN3+ specificity was 64.8% (95% CI: 58.1-71.5) for combined triage, and 78.6% (95% CI: 72.8-84.3) for sole cytology triage testing. For CIN2+, the sensitivity of combined triage testing was 84.5% (95% CI: 75.2-93.8) versus 65.5% (95% CI: 53.3-77.7) for sole cytology triage, with corresponding specificities of 69.9% (95% CI: 63.1-76.6) and 83.5% (95% CI: 78.0-89.0), respectively. In conclusion, combined triage reached substantially higher CIN2+/3+ sensitivities compared to sole cytology at a slight drop in specificity. Therefore, it is an attractive triage strategy for colposcopy of hrHPV-positive women with a high reassurance for cervical cancer and advanced CIN lesions.
    06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: We determined whether the participation rate for a brush-based cervicovaginal self-sampling device is non-inferior to the participation rate for a lavage-based one for testing for hrHPV (high-risk human papillomavirus). Additionally, positivity rates for hrHPV, the detection rates for cervical intraepithelial neoplasia grades 2 and 3 or worse (CIN2+/3+), and user comfort were compared. A total of 35,477 non-responders of the regular cervical screening programme aged 33-63 years were invited to participate. Eligible women (n=30,130) were randomly assigned to receive either a brush-based or a lavage-based device, and a questionnaire for reporting user convenience. Self-sampling responders testing hrHPV-positive were invited for a physician-taken sample for cytology; triage-positive women were referred for colposcopy. A total of 5218 women participated in the brush-based sampling group (34.6%) and 4809 women in the lavage-based group (31.9%), i.e. an absolute difference of 2.7% (95%CI 1.8-4.2). The hrHPV-positivity rates in the two groups were identical (8.3%, relative risk (RR) 0.99, 95%CI 0.87-1.13). The detection of CIN2+ and CIN3+ in the brush group (2.0% for CIN2+; 1.3% for CIN3+) was similar to that in the lavage group (1.9% for CIN2+; 1.0% for CIN3+) with a cumulative RR of 1.01, 95%CI 0.83-1.24 for CIN2+ and 1.25, 95%CI 0.92-1.70 for CIN3+. The two self-sampling devices performed similarly in user comfort. In conclusion, offering a brush-based device to non-responders is non-inferior to offering a lavage-based device in terms of participation. The two self-sampling methods are equally effective in detecting hrHPV, CIN2+/CIN3+ and are both well accepted. © 2014 Wiley Periodicals, Inc.
    International journal of cancer. Journal international du cancer. 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Infection of cervical epithelium with high-risk human papilloma virus (hrHPV) might result in productive or transforming cervical intraepithelial neoplasia (CIN) lesions, the morphology of which can overlap. In transforming CIN lesions, aberrations in host cell genes accumulate over time, which is necessary for the ultimate progression to cancer. On the basis of (epi)genetic changes, early and advanced transforming CIN lesions can be distinguished. This paves the way for new molecular tools for cervical screening, diagnosis and management of cervical cancer precursor lesions.
    Nature reviews. Cancer. 05/2014; 14(6):395-405.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Women treated for high-grade cervical disease (cervical intraepithelial neoplasia grade 2 or grade 3 [CIN 2/3]) face a significant risk of developing post-treatment disease. Therefore, in most European countries, they are monitored by cytologic testing at 6, 12, and 24 months after treatment. Although testing for high-risk types of the human papillomavirus (hrHPV) in the follow-up seems to be a valuable supplementary method, its use is not yet fully explored. Besides reviewing the literature, we completed a long-term follow-up study describing the cumulative risk for CIN 2/3 or cancer (CIN 2+) of different hrHPV and cytology test results after treatment. High-risk HPV testing improves the sensitivity to detect posttreatment CIN 2/3 (relative sensitivity = 1.15, 95% confidence interval [CI] = 1.06-1.25), but the highest sensitivity (95%, 95% CI = 91%-98%) is reached by performing cotesting (both cytology and hrHPV). The CIN 2+ risk after a single negative cotesting result taken 6 months after treatments was similar to the risk after 3 consecutive negative cytologic test results (5-y CIN 2+ risk being 3.0% [95% CI = 1.5%-6.1%] and 2.9% [95% CI = 1.2%-7.1%], respectively). Women who test negative for cotesting at both 6 and 24 months after treatment have a minimal risk of developing CIN 3+ in the next 5 years (0.0%, 95% CI = 0.0%-3.0%). We propose a new posttreatment surveillance protocol, consisting of combined testing with both cytology and hrHPV at 6 and 24 months after treatment. After 2 negative cotesting results, women should be retested after 5 years.
    Journal of Lower Genital Tract Disease 04/2014; · 1.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: High attendance rates in cervical screening are essential for effective cancer prevention. Offering HPV-self-sampling to non-responders increases participation rates. The objectives of this study were to determine why non-responders do not attend regular screening, and why they do or do not participate when offered a self-sampling device. A questionnaire study was conducted in the Netherlands from October 2011 to December 2012. 35,477 non-responders were invited to participate in an HPV-self-sampling study; 5,347 women did opt-out. Finally, 30,130 women received a questionnaire and self-sampling device. The analysis was based on 9,484 returned questionnaires (31.5%) with a self-sample specimen, and 682 (2.3%) without. Among women who returned both, the main reason for non-attendance to cervical screening was that they forgot to schedule an appointment (3,068; 32.3%). The most important reason to use the self-sampling device was the opportunity to take a sample in their own time-setting (4,763; 50.2%). 30.9% of the women who did not use the self-sampling device preferred after all to have a cervical smear taken instead. Organisational barriers are the main reason for non-attendance in regular cervical screening. Important reasons for non-responders to the regular screening to use a self-sampling device are convenience and self-control.
    Preventive Medicine 04/2014; · 3.50 Impact Factor
  • The Lancet 04/2014; 383(9925):1295. · 39.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In view of possible type replacement upon introduction of human papillomavirus (HPV) vaccination, we aimed to explore patterns of type-specific clustering across populations with various background infection risks. A total of 3,874 women from 3 cross-sectional studies in the Netherlands (in 2007-2009) provided vaginal self-samples, which were tested for 25 HPV genotypes by a sensitive molecular assay (SPF10 line probe assay, DDL Diagnostic Laboratory, Voorburg, the Netherlands). The number of concurrent HPV infections per woman was studied by Poisson regression. Associations between HPV types were investigated by generalized estimating equation analyses. The prevalence of any HPV type was 14% in a population-based study, 54% in a chlamydia screening intervention study, and 73% in a study among attendees of sexually transmitted infection clinics. Overall, multiple HPV infections were detected in 26% of the women. The number of concurrent HPV infections conformed to an overdispersed Poisson distribution, even after correction for known risk factors. Types differed significantly in their tendencies to be involved in coinfections, but no evidence for particular type-type interactions was found. Moreover, the strongest associations were observed in the lowest-risk population and vice versa.We found no indications of pairwise interactions, but our findings do suggest that clustering differs among HPV types and varies across risk groups.
    American journal of epidemiology 04/2014; · 5.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We evaluated compliance with human papilloma virus (HPV) testing and risk-adapted patient pathways and monitored changes in high-grade cervical disease during long-term follow-up. Women aged >30 years attending routine screening for cervical cancer were managed according to results from first-round screening tests (cytology and high-risk HPV; Hybrid Capture 2). Between February 2006 and January 2011, 19,795/19,947 women agreed to participate, of whom 4067 proceeded to a second screening round 5 years after recruitment. Predefined endpoints were compliance, grade 3 cervical intraepithelial neoplasia or cancer (CIN3+), new HPV infection, HPV persistence, and abnormal smears in round 2. 765/19,795 women (3.9%) in round 1 and 41/4067 (1.0%) in round 2 were referred for colposcopy. Compliance rates with colposcopy were 93.1% and 92.7%, respectively, while histological assessment was performed in 680/712 (95.5%) and 36/38 (94.7%), respectively. CIN3+ rates were 172/19,795 (0.87%; 95% confidence intervals 0.7 to 1.0) in round 1 and 2/4064 (0.05%; 95% confidence intervals 0.006 to 0.2) in round 2; the difference was statistically significant (Fisher Exact test, P<0.001). After 5 years, the incidence of new HPV infection was 124/3906 (3.2%) and HPV persistence was observed in 22/161 (13.7%). Locally organised HPV/cytology co-testing is feasible and acceptable to women. Risk-adapted management rapidly detected a high rate of prevalent CIN3+ while the subsequent long-term risk of new high-grade cervical disease was surprisingly low. It remains unclear if this phenomenon is explained by CIN3 mostly occurring early in life or by modifying the natural course of HPV infection with colposcopy and histological assessment. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 02/2014; · 6.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cytology is a widely used method of triaging women who test positive for human papillomavirus (HPV). However, self-sampled specimens, which can substantially increase participation in screening programmes, are not suitable for accurate cytological assessment. We investigated whether direct DNA methylation-based molecular triage on self-sampled cervicovaginal specimens was non-inferior to cytology triage on additional physician-collected cervical samples in the detection of cervical intraepithelial neoplasia grade 2 (CIN2) or worse in women who did not attend cervical screening programmes. In this randomised controlled non-inferiority trial, we invited women (aged 33-63 years) registered as non-attendees of cervical screening in the Netherlands in 2007 to submit a self-collected cervicovaginal sample for HPV testing. Using a computer-generated sequence, we randomly allocated women who tested positive for high-risk hrHPV on a self-sample to either triage by cytology on an additional physician-taken smear or direct triage on the self-sample by methylation analysis of MAL and miR-124-2 genes (1:1; stratified by age and region, with block sizes by age group). Triage-positive women in either group were referred for colposcopy. The primary endpoint was detection of CIN2 or worse, analysed by intention to treat. The non-inferiority margin was 0·80. This study is registered in the Primary Trial Register of the Netherlands, number NTR6026. We invited 46 001 women to participate, 12 819 of whom returned self-sampled material; 1038 samples tested positive for high-risk HPV. Between Nov 1, 2010, and Dec 31, 2011, after exclusion of women who were ineligible, we enrolled and randomly allocated 515 women to methylation triage and 509 to cytology triage. The detection of CIN2 or worse with methylation triage was non-inferior to that with cytology triage (90 [17%] of 515 women vs 75 [15%] of 509 women; relative risk 1·19, 95% CI 0·90-1·57). Referral for colposcopy was more common in the molecular group (284 [55%] women) than in the cytology group (149 [29%] women; p<0·0001). Mean time to CIN2 or worse diagnosis was shorter in the molecular triage group (96 days, range 44-101) than in the cytology triage group (158 days, 71-222; p=0·00084). DNA methylation analysis of MAL and miR-124-2 genes on HPV-test-positive self-samples is non-inferior to cytology triage in the detection of CIN2 or worse, opening the way to full molecular screening. Midden-West and Oost Screening Organisations and Stichting Achmea Gezondheidszorg.
    The Lancet Oncology 02/2014; · 25.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background:Women with borderline/mildly dyskaryotic (BMD) cytology smears are currently followed up with repeat testing at 6 and 18 months. The objective of this study is to analyse the cross-sectional and longitudinal performance of p16/Ki-67 dual-stained cytology for the detection of cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) and CIN2+ in women with BMD, and to compare the results with baseline human papillomavirus (HPV) testing.Methods:Conventional Pap cytology specimens of 256 women with BMD were dual stained for p16/Ki-67 retrospectively, and compared with baseline HPV results and long-term follow-up results.Results:p16/Ki-67 dual-stained cytology showed a sensitivity of 100%, a specificity of 64.4% and a negative predictive value (NPV) of 100.% for CIN3+. Human papillomavirus testing demonstrated similar sensitivity (96.3%), and NPV (99.1%), but a significantly lower specificity (57.6%; P=0.024) for CIN3+. Sensitivity, specificity and NPV for CIN2+ of dual-stained cytology were 89.7%, 73.1% and 95.1%, respectively, which was similar when compared with HPV testing. Dual-stained cytology showed a significant lower referral rate than HPV testing (43.6% vs 49.1%; P=0.043). During long-term follow-up, no CIN3+ lesions developed in HPV-positive, dual-stained negative women.Conclusions:Comparable sensitivity and NPV of dual-stained cytology for CIN3+, combined with a significantly higher specificity, makes p16/Ki-67 dual-stained cytology a viable alternative to HPV testing for triaging BMD.British Journal of Cancer advance online publication, 11 February 2014; doi:10.1038/bjc.2014.34 www.bjcancer.com.
    British Journal of Cancer 02/2014; 110(6):1579-1586. · 5.08 Impact Factor
  • Chris J L M Meijer, Peter J F Snijders
    Nature Reviews Clinical Oncology 01/2014; · 15.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cytology-based nation-wide cervical screening has led to a substantial reduction of the incidence of cervical cancer in western countries. However, the sensitivity of cytology for the detection of high-grade precursor lesions or cervical cancer is limited; therefore, repeated testing is necessary to achieve program effectiveness. Additionally, adenocarcinomas and its precursors are often missed by cytology. Consequently, there is a need for a better screening test. The insight that infection with high-risk human papillomavirus (hrHPV) is the causal agent of cervical cancer and its precursors has led to the development of molecular tests for the detection of hrHPV. Strong evidence now supports the use of hrHPV testing in the prevention of cervical cancer. In this review, we will discuss the arguments in favor of, and concerns on aspects of implementation of hrHPV testing in primary cervical cancer screening, such as the age to start hrHPV-based screening, ways to increase screening attendance, requirements for candidate hrHPV tests to be used, and triage algorithms for screen-positive women.
    Annals of Oncology 01/2014; · 7.38 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Methylation markers were studied for their suitability to triage human papillomavirus (HPV)-positive women by testing self-collected cervico-vaginal lavage specimens. For this purpose, we analyzed 355 hrHPV-positive self-collected specimens with three methylation markers, that is, CADM1-m18, MAL-m1 and miR-124-2 by quantitative methylation-specific PCR. The areas under the receiver-operating characteristic (ROC) curve for end-point cervical intraepithelial neoplasia grade 3 or worse (CIN3+) were 0.637 for CADM1-m18, 0.767 for MAL-m1 and 0.762 for miR-124-2. This indicates that CADM1-m18 is not suitable as single marker. By varying the thresholds of both markers in the bi-marker panels CADM1-m18/MAL-m1, CADM1-m18/miR-124-2 and MAL-m1/miR-124-2 upper and lower ROC curves were obtained, depicting the maximum and minimum CIN3+ sensitivity, respectively, at given specificity. For all these bi-marker combinations, the upper curves were similar. However, for the MAL-m1/miR-124-2 panel, the distance between upper and lower ROC curves was closest and this panel displayed the highest assay thresholds, indicating that this combination was most robust. At clinical specificities of 50 and 70%, the MAL-m1/miR-124-2 sensitivity for detection of CIN3+ ranged from 77.0 to 87.8% and from 64.9 to 71.6%, respectively. At 70% specificity thresholds no carcinomas were missed. By comparison, the CIN3+ sensitivity of HPV16/18 genotyping on the self-sampled lavage specimens was 58.1% (95%CI: 46.6-68.8) at a specificity of 87.7% (95%CI: 83.2-91.2). In conclusion, methylation analysis is a promising triage tool that in combination with HPV-DNA testing offers feasible, full molecular screening on self-collected cervico-vaginal lavage specimens.
    International Journal of Cancer 01/2014; · 6.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background In four randomised trials, human papillomavirus (HPV)-based screening for cervical cancer was compared with cytology-based cervical screening, and precursors of cancer were the endpoint in every trial. However, direct estimates are missing of the relative efficacy of HPV-based versus cytology-based screening for prevention of invasive cancer in women who undergo regular screening, of modifiers (eg, age) of this relative efficacy, and of the duration of protection. We did a follow-up study of the four randomised trials to investigate these outcomes. Methods 176 464 women aged 20–64 years were randomly assigned to HPV-based (experimental arm) or cytology-based (control arm) screening in Sweden (Swedescreen), the Netherlands (POBASCAM), England (ARTISTIC), and Italy (NTCC). We followed up these women for a median of 6·5 years (1 214 415 person-years) and identified 107 invasive cervical carcinomas by linkage with screening, pathology, and cancer registries, by masked review of histological specimens, or from reports. Cumulative and study-adjusted rate ratios (experimental vs control) were calculated for incidence of invasive cervical carcinoma. Findings The rate ratio for invasive cervical carcinoma among all women from recruitment to end of follow-up was 0·60 (95% CI 0·40–0·89), with no heterogeneity between studies (p=0·52). Detection of invasive cervical carcinoma was similar between screening methods during the first 2·5 years of follow-up (0·79, 0·46–1·36) but was significantly lower in the experimental arm thereafter (0·45, 0·25–0·81). In women with a negative screening test at entry, the rate ratio was 0·30 (0·15–0·60). The cumulative incidence of invasive cervical carcinoma in women with negative entry tests was 4·6 per 105 (1·1–12·1) and 8·7 per 105 (3·3–18·6) at 3·5 and 5·5 years, respectively, in the experimental arm, and 15·4 per 105 (7·9–27·0) and 36·0 per 105 (23·2–53·5), respectively, in the control arm. Rate ratios did not differ by cancer stage, but were lower for adenocarcinoma (0·31, 0·14–0·69) than for squamous-cell carcinoma (0·78, 0·49–1·25). The rate ratio was lowest in women aged 30–34 years (0·36, 0·14–0·94). Interpretation HPV-based screening provides 60–70% greater protection against invasive cervical carcinomas compared with cytology. Data of large-scale randomised trials support initiation of HPV-based screening from age 30 years and extension of screening intervals to at least 5 years. Funding European Union, Belgian Foundation Against Cancer, KCE-Centre d'Expertise, IARC, The Netherlands Organisation for Health Research and Development, the Italian Ministry of Health.
    The Lancet 01/2014; 383(9916):524–532. · 39.06 Impact Factor
  • The Lancet 01/2014; 383(9925):1295. · 39.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives High attendance rates in cervical screening are essential for effective cancer prevention. Offering HPV self-sampling to non-responders increases participation rates. The objectives of this study were to determine why non-responders do not attend regular screening, and why they do or do not participate when offered a self-sampling device. Methods A questionnaire study was conducted in the Netherlands from October 2011 to December 2012. A total of 35,477 non-responders were invited to participate in an HPV self-sampling study; 5347 women did opt out. Finally, 30,130 women received a questionnaire and self-sampling device. Results The analysis was based on 9484 returned questionnaires (31.5%) with a self-sample specimen, and 682 (2.3%) without. Among women who returned both, the main reason for non-attendance to cervical screening was that they forgot to schedule an appointment (3068; 32.3%). The most important reason to use the self-sampling device was the opportunity to take a sample in their own time-setting (4763; 50.2%). A total of 30.9% of the women who did not use the self-sampling device preferred after all to have a cervical smear taken instead. Conclusions Organisational barriers are the main reason for non-attendance in regular cervical screening. Important reasons for non-responders to the regular screening to use a self-sampling device are convenience and self-control.
    Preventive Medicine. 01/2014; 64:108–113.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Epidemiological studies identified 12 high-risk HPV (hrHPV) types and 8 probably/possibly hrHPV types which display different cancer risks. Functional studies on transforming properties of hrHPV are mainly limited to HPV16 and 18, which induce immortalization of human foreskin keratinocytes (HFKs) by successive bypass of two proliferative lifespan barriers, senescence and crisis. Here, we systematically compared the in vitro immortalization capacities as well as influences on p53, pRb, hTERT, growth behavior, and differentiation capacity of nine hrHPV types (HPV16/18/31/33/35/45/51/52/59), and two probably hrHPV types (HPV66/70). By retroviral transduction the respective E6E7 coding sequences were expressed in HFKs of two to three independent donors.Reduced p53 levels and low level hTERT expression in early passage cells, as seen in HPV16/31/33/35, and to a lesser extent HPV18 transduced HFKs, was associated with continuous growth and an increased immortalization capacity. Less frequent immortalization by HPV45/51 and immortalization by HPV66/70 was preceded by an intervening period of strongly reduced growth (crisis) without prior increase in hTERT expression. Immortalization by HPV59 was also preceded by a period crisis, despite the onset of low hTERT expression at early passage. HPV52 triggered an extended lifespan, but failed to induce immortality. Variations in p53 and pRb levels were not correlated to differences in alternative E6E7 mRNA splicing in all hrHPV transduced HFKs. On collagen rafts, transductants showed disturbed differentiation reminiscent of precancerous lesions.In conclusion, the in vitro oncogenic capacity differs between the established hrHPV types and both some established and probably hrHPV types display weak or moderate immortalization potential.
    Journal of Virology 11/2013; · 5.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We recently identified a DNA copy number aberration (CNA)-based classifier, including changes at 3p26.3-p11.1, 3q26.2-29, and 6p25.3-24.3, as a risk predictor for cancer in individuals presenting with endobronchial squamous metaplasia. The current study was set out to validate the prediction accuracy of this classifier in an independent series of endobronchial squamous metaplastic and dysplastic lesions.The study included 36 high-risk subjects who had endobronchial lesions of various histological grades that were identified and biopsied by autofluorescence bronchoscopy and were subjected to arrayCGH in a nested case-control design. Of the 36 patients, 12 had a carcinoma in situ or invasive carcinoma at the same site at follow-up (median 11 months, range 4-24), while 24 controls remained cancer free (78 months, range 21-142).The previously defined CNA-based classifier demonstrated 92% (95% CI 77% to 98%) accuracy for cancer (in situ) prediction. All nine subjects with CNA-based classifier-positive endobronchial lesions at baseline experienced cancer outcome, whereas all 24 controls and 3 cases were classified as being low risk.In conclusion, CNAs prove to be a highly accurate biomarker for assessing the progression risk of endobronchial squamous metaplastic and dysplastic lesions. This classifier could assist in selecting subjects with endobronchial lesions who might benefit from more aggressive therapeutic intervention or surveillance.
    Thorax 11/2013; · 8.38 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There are very few data from men on the risk of HIV acquisition associated with penile human papillomavirus (HPV) infection and no data on the potential modifying effect of male circumcision. Therefore, this study evaluated whether HPV is independently associated with risk of HIV. A cohort study of HPV natural history nested within a randomized control trial of male circumcision to reduce HIV incidence in Kisumu, Kenya. Prospective data from 2519 men were analyzed using 6-month discrete-time Cox models to determine if HIV acquisition was higher among circumcised or uncircumcised men with HPV compared to HPV-uninfected men. Risk of HIV acquisition was nonsignificantly increased among men with any HPV [adjusted hazard ratio (aHR) 1.72; 95% confidence interval (CI) 0.94-3.15] and high-risk HPV (aHR 1.92; 95% CI 0.96-3.87) compared to HPV-uninfected men, and estimates did not differ by circumcision status. Risk of HIV increased 27% with each additional HPV genotype infection (aHR 1.27; 95% CI 1.09-1.48). Men with persistent (aHR 3.27; 95% CI 1.59-6.72) or recently cleared (aHR 3.05; 95% CI 1.34-6.97) HPV had a higher risk of HIV acquisition than HPV-uninfected men. Consistent with the findings in women, HPV infection, clearance, and persistence were associated with an increased risk of HIV acquisition in men. Given the high prevalence of HPV in populations at risk of HIV, consideration of HPV in future HIV-prevention studies and investigation into mechanisms through which HPV might facilitate HIV acquisition are needed.
    AIDS (London, England) 10/2013; · 4.91 Impact Factor

Publication Stats

45k Citations
5,533.60 Total Impact Points

Institutions

  • 2005–2014
    • Centro di Riferimento per l'Epidemiologia e la Prevenzione Oncologica in Piemonte
      Torino, Piedmont, Italy
  • 2001–2014
    • VU University Medical Center
      • • Department of Pathology
      • • Department of Epidemiology and Biostatistics
      Amsterdamo, North Holland, Netherlands
    • Vanderbilt University
      Nashville, Michigan, United States
    • Instituto Nacional de Salud Pública
      • The Center for Population Health Research
      Cuernavaca, Morelos, Mexico
  • 1984–2014
    • VU University Amsterdam
      • • Department of Pathology
      • • Oral Pathology and Maxillofacial Surgery Section
      • • Department of Obstetrics and Gynaecology
      Amsterdamo, North Holland, Netherlands
  • 2009–2013
    • DDL Diagnostic Laboratory
      Rijswijk, South Holland, Netherlands
  • 2005–2013
    • International Agency for Research on Cancer
      Lyons, Rhône-Alpes, France
  • 2012
    • Reinier de Graaf Groep
      • Department of Gynecology and Obstetrics
      Delft, South Holland, Netherlands
  • 2007–2012
    • University of North Carolina at Chapel Hill
      • Department of Epidemiology
      Chapel Hill, NC, United States
  • 2005–2012
    • Erasmus MC
      • • Department of Obstetrics and Gynaecology
      • • Department of Pathology
      Rotterdam, South Holland, Netherlands
  • 1983–2012
    • University of Amsterdam
      • • Swammerdam Institute for Life Sciences
      • • Department of Pathology
      • • Department of Dermatology
      • • Department of Obstetrics and Gynaecology
      Amsterdamo, North Holland, Netherlands
  • 1970–2012
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Pathology
      Amsterdamo, North Holland, Netherlands
  • 2011
    • Institut National de Santé Publique du Québec (INSPQ)
      Québec, Quebec, Canada
    • Shahid Beheshti University of Medical Sciences
      Teheran, Tehrān, Iran
    • Johns Hopkins Bloomberg School of Public Health
      • Department of Epidemiology
      Baltimore, MD, United States
    • Queen Mary, University of London
      • Centre for Cancer Prevention
      London, ENG, United Kingdom
  • 1999–2011
    • Institut Català d'Oncologia
      Barcino, Catalonia, Spain
    • University of Antwerp
      • Departement Oncologie
      Antwerpen, VLG, Belgium
  • 2010
    • KIST Medical College
      Lalitpur, Central Region, Nepal
  • 2005–2009
    • Erasmus Universiteit Rotterdam
      • Department of Obstetrics and Gynaecology
      Rotterdam, South Holland, Netherlands
  • 1978–2009
    • Leiden University Medical Centre
      • • Department of Dermatology
      • • Department of Pathology
      Leiden, South Holland, Netherlands
  • 2008
    • Maria Sklodowska Curie Memorial Cancer Centre
      Gleiwitz, Silesian Voivodeship, Poland
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands
    • Cancer Research UK
      Londinium, England, United Kingdom
  • 2003–2007
    • Albert Schweitzer Ziekenhuis
      Dordt, South Holland, Netherlands
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
    • National Cancer Institute Thailand
      Krung Thep, Bangkok, Thailand
    • University of Buenos Aires
      Buenos Aires, Buenos Aires F.D., Argentina
    • National Cancer Center Korea
      Kōyō, Gyeonggi Province, South Korea
  • 1996–2007
    • Netherlands Cancer Institute
      • Department of Pathology
      Amsterdam, North Holland, Netherlands
    • University Medical Center Utrecht
      • Department of Pathology
      Utrecht, Provincie Utrecht, Netherlands
  • 2006
    • Belgian Scientific Institute for Public Health
      Bruxelles, Brussels Capital Region, Belgium
    • Rijnstate Hospital
      Arnheim, Gelderland, Netherlands
  • 1996–2005
    • Danish Cancer Society
      København, Capital Region, Denmark
  • 1981–2005
    • Leiden University
      Leyden, South Holland, Netherlands
  • 2004
    • University of Ibadan
      • College of Medicine
      Ibadan, Oyo State, Nigeria
  • 2002
    • Institut National de Recherche en Santé Publique
      Nouakchot, Nouakchott, Mauritania
    • Akademiska Sjukhuset
      Uppsala, Uppsala, Sweden
  • 2000
    • Karolinska Institutet
      Solna, Stockholm, Sweden
  • 1998
    • Institut National d'Oncologie, Rabat
      Rabat, Rabat-Salé-Zemmour-Zaër, Morocco
    • Prince of Songkla University
      • Faculty of Medicine
      Songkhla, Changwat Songkhla, Thailand
    • Philippine General Hospital
      Manila, National Capital Region, Philippines
  • 1997–1998
    • Statens Serum Institut
      • Department of Epidemiology Research
      Copenhagen, Capital Region, Denmark
  • 1991–1996
    • Academisch Centrum Tandheelkunde Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 1994
    • University of São Paulo
      • Departamento de Medicina Preventiva (FM) (São Paulo)
      São Paulo, Estado de Sao Paulo, Brazil
  • 1993
    • Utrecht University
      Utrecht, Utrecht, Netherlands
  • 1985–1992
    • University of the Free State
      Bloemfontein, Free State, South Africa
  • 1990–1991
    • The Australian Society of Otolaryngology Head & Neck Surgery
      Evans Head, New South Wales, Australia
  • 1987
    • Radboud University Nijmegen
      • Department of Pathology
      Nymegen, Gelderland, Netherlands