W G Quint

DDL Diagnostic Laboratory, Rijswijk, South Holland, Netherlands

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Publications (348)1551.24 Total impact

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    ABSTRACT: Eight HPV types (HPV26, 53, 66, 67, 68, 70, 73 and 82) that are phylogenetically closely related to 12 WHO-defined high-risk (HR-)HPV have been rarely but consistently identified as single HPV infections in about 3% of cervical cancer (CxCa) tissues. Due to lack of biological data, these types are referred to as probable/possible (p)HR-HPV. To analyze their biological activity in direct comparison to HR-HPV types, we selected 55 formalin-fixed paraffin-embedded (FFPE) CxCa tissues harboring single pHR-HPV infections (2-13 cases per type) and 266 tissues harboring single HR-HPV (7-40 cases per type) from a worldwide, retrospective, cross-sectional study. Single HPV infection was verified by two genotyping methods. Presence of type-specific spliced E6*I mRNA transcripts and expression of cellular proteins indicative of HPV transformation were assessed in all cases. In 55 CxCa tissues with pHR-HPV, E6*I mRNA expression was 100%, high p16INK4a, 98%; low pRb, 96%; low CyD1, 93% and low p53, 84%. Compared to HPV16 tissues as a reference, individual frequencies of these five markers did not differ significantly, either for any of the eight pHR-HPV and the 11 other HR-types individually, or for the groups of pHR- and HR-types without HPV16. We conclude that the eight pHR-HPV types, when present as a single infection in CxCa, are biologically active and affect the same cellular pathways as any of the fully-recognized carcinogenic HR-HPV types. Therefore we have provided molecular evidence of carcinogenicity for types currently classified as probably/possibly carcinogenic. Although this evidence is crucial for HPV type carcinogenicity classification, per se it is not sufficient for inclusion of these HPV types into population-wide primary and secondary prevention programs. Such decisions have to include careful estimation of effectiveness and cost-benefit analyses.
    The Journal of Pathology 07/2014; · 7.59 Impact Factor
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    ABSTRACT: One third of primary Dutch school children have cutaneous warts and each year around 20% of them seek medical treatment. However, little is known about the epidemiology of the HPV types causing these warts. In three primary school classes, the distribution of cutaneous wart-associated HPV types was investigated in skin swabs taken from the forehead, hand dorsum and sole of the foot of all children, and from any warts.
    The British journal of dermatology. 06/2014;
  • The Journal of infectious diseases. 06/2014;
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    ABSTRACT: In this open, extended follow-up study (NCT00929526, Clinicaltrials.gov), we evaluated the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine efficacy, immunogenicity and safety up to 4 years after first vaccination in Japanese women aged 20-25 years. In the initial randomized, double-blind study (NCT00316693), 1040 women received the study vaccine or hepatitis A control vaccine; 752 women were included in the follow-up study. In women from the according-to-protocol efficacy cohort (ATP-E), who were initially seronegative for the HPV type analyzed, no cervical intraepithelial neoplasia (CIN) grade 1 or greater (CIN1+) cases associated with HPV-16/18 were reported in the HPV group, while in the control group, 5 cases were identified in extended follow-up analyses (vaccine efficacy [VE] 100% [95% CI: -3.7-100]) and 8 cases in combined initial and follow-up studies analyses (VE 100% [42.2-100]). In the ATP-E, VE against CIN1+ and CIN2+ associated with high-risk HPV types reached 66.4% (21.6-87.1) and 83.0% (22.1-98.2) in extended follow-up analyses, and 63.4% (28.8-82.3) and 77.3% (30.4-94.4) in analyses of combined studies, respectively. During the four-year period, protection against CIN1+ and CIN2+, irrespective of the HPV type, was 56.7% (32.8-72.6) and 54.9% (20.5-75.3) in women receiving ≥ 1 vaccine dose, regardless of baseline serostatus (total vaccinated cohort [TVC]) and 61.0% (11.8-84.2) and 73.9% (1.1-95.3) in women naïve to HPV infection at baseline (TVC-naïve), respectively. The high VE observed in Japanese women, accompanied by a sustained immune response and a clinically acceptable safety profile, support findings of large, international trials.
    Human vaccines & immunotherapeutics. 04/2014; 10(7).
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    ABSTRACT: Several assays are used to measure type-specific serological responses to human papillomavirus (HPV), including the bead-based glutathione S-transferase (GST)-L1 multiplex serology assay and virus-like particle (VLP)-based ELISA. We evaluated the high-throughput GST-L1, which is increasingly used in epidemiologic research, as a measure of cumulative HPV infection and future immune protection among HPV-unvaccinated women. We tested enrollment sera from participants in the control arm of the Costa Rica Vaccine Trial (n = 488) for HPV16 and HPV18 using GST-L1, VLP-ELISA, and two assays that measure neutralizing antibodies (cLIA and SEAP-NA). With statistical adjustment for sampling, we compared GST-L1 serostatus to established HPV seropositivity correlates and incident cervical HPV infection using odds ratios. We further compared GST-L1 to VLP-ELISA using pair-wise agreement statistics and by defining alternate assay cutoffs. Odds of HPV16 GST-L1 seropositivity increased with enrollment age (OR = 1.20 per year, 95%CI 1.03-1.40) and lifetime number of sexual partners (OR = 2.06 per partner, 95%CI 1.49-2.83), with similar results for HPV18. GST-L1 seropositivity did not indicate protection from incident infection over 4 years of follow-up (HPV16 adjusted OR = 1.72, 95%CI 0.95-3.13; HPV18 adjusted OR = 0.38, 95%CI 0.12-1.23). Seroprevalence by GST-L1 (HPV16 and HPV18, respectively) was 5.0% and 5.2%, compared to 19.4% and 23.8% by VLP-ELISA, giving positive agreement of 39.2% and 20.8%. Lowering GST-L1 seropositivity cutoffs improved GST-L1/VLP-ELISA positive agreement to 68.6% (HPV16) and 61.5% (HPV18). Our data support GST-L1 as a marker of cumulative HPV infection, but not immune protection. At lower seropositivity cutoffs, GST-L1 better approximates VLP-ELISA.
    BMC Infectious Diseases 03/2014; 14(1):120. · 3.03 Impact Factor
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    ABSTRACT: Persistent cervical high-risk human papillomavirus (HR-HPV) infection results in high-grade cervical intraepithelial neoplasia (CIN2/3) and cervical carcinoma. The susceptibility of the cervix to HPV carcinogenesis and the importance of HPV18 in cervical carcinoma despite relative infrequency in CIN2/3 could be linked to HR-HPV infection of immature metaplasia (IM) at the squamocolumnar junction. Atypical IM (AIM) is an equivocal category used to describe changes in IM suggestive of high-grade neoplasia, which causes diagnostic and management problems. We used laser capture microscopy combined with polymerase chain reaction in 24 women with HPV18, HPV16, or other HPV infections on cytologic analysis and a cervical loop electrosurgical excision procedure to locate HR-HPV in cervical tissue. HPV18-positive AIM and CIN2/3 were present in 7/12 cases with HPV18 on cytologic analysis. In 2 cases with HPV18 and other HPV types, HPV18 was only present in AIM and not in CIN2/3. HPV16-positive AIM was present in 3/7 and HPV16-positive CIN2/3 in 5/7 cases with HPV16. No cases had HPV16 AIM without CIN2/3. Other HR-HPV-positive AIM and CIN2/3 cases were present, respectively, in 1/6 and 5/6 cases positive for HR-HPV types other than HPV16/18. In a subset, 94% HPV18 AIM regions showed CK17 and p16 positivity, and 41% were CK7 positive. CIN2/3 and AIM with other HR-HPVs showed similar patterns. AIM was a particular feature of HPV18 infection in women with CIN2/3. HR-HPV infection of CK7/17-positive AIM expressing p16 was particularly seen for HPV18 with and without classical CIN2/3 and should be regarded as a high-grade precancer.
    The American journal of surgical pathology 02/2014; · 4.06 Impact Factor
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    ABSTRACT: Background. High-grade anal intraepithelial neoplasia (HGAIN) is present in many HIV+ men-who-have-sex-with-men (MSM). The major etiologic factor is infection with an oncogenic human papilloma virus (HPV). We investigated whether individual components of HGAIN are caused by single HPV types.Methods. DNA was isolated from 31 HGAIN whole tissue sections (WTS) of 21 HIV+ MSM and analysed by the SPF10 PCR/LiPA25 HPV genotyping system. In WTS with multiple HPV types, PCR was repeated in regions of AIN sampled by laser-capture-microdissection (LCM). The results were compared with HPV types in anal swabs.Results. A single HPV type was observed in 15 (48%) of 31 WTS. In an additional 14 WTS, one HPV type was found in each LCM lesion sample. Consequently, in 29/31 (94%) biopsies a single HPV type was found in each lesional component studied. 2 WTS contained collision regions with each 2 HPV types. HPV 16 was presumed causative in 14/31 biopsies (45%). More than half of the anal swabs did not contain all causative HPV types.Conclusions. Individual components of HGAIN are caused by single HPV types ("one lesion, one virus"). HPV 16 is causative in less than 50%. Anal swabs are not useful for detecting lesion specific HPV types.
    The Journal of Infectious Diseases 01/2014; · 5.85 Impact Factor
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    ABSTRACT: Objective This retrospective registry-based study aimed to assess the human papillomavirus (HPV)-type distribution in primary and recurrent high-grade cervical intraepithelial neoplasia (CIN2 +), and to discriminate pre-existing from newly-acquired infections. Methods Cervical specimens from 58 women (median age (Q1-Q3): 37.6 (31.7-44.9)) who underwent primary (1998–2003) and repeat conization were confirmed as CIN2 + during expert pathology review. HPV testing was performed using PCR MP-TS123 Luminex for 16 HPV types. Molecular HPV16 E6 and HPV18 LCR DNA sequencing was performed on specimens with persistent HPV16/18. Results All 58 paired cones were HPV positive; 49 had CIN3 + in the primary cone. Forty-seven (95.9%) women with primary CIN3 + and recurrent CIN2 + had persistent high-risk (hr)HPV infection, of which 74.5% were HPV16/18. Two women had probable newly-acquired HPV16/52/56 and HPV39 infection. One woman with persistent HPV52 also had a probable new HPV16 E6 variant in the recurrent CIN2 +. Median time delay (Q1-Q3) between conizations was 2.0y (1.1-4.0), being shorter for women older than 40y: 2.6y (1.1-3.7) than for women younger than 40y: 6.0y (2.0-8.7). Primary conization histology revealed CIN3, cervical adenocarcinoma in situ and micro invasive carcinomas in 43 (87.8%), 5 (10.2%) and 1 (2.0%) women, respectively. Primary HPV16- and HPV18-infected CIN3 + had a shorter delay between conizations: 1.8y (1.2-4.4) and 2.2y (0.4-NE), respectively, compared to HPV33-:3.8y (3.3-7.8) or other HPV type-infected: 8.2y (6.0-NE) CIN3 + . Conclusions Routine post-conization hr-HPV DNA testing together with cervical cytology may provide a better prediction for potential recurrent disease. Further, primary prevention through adolescent vaccination may prevent CIN2 + and its recurrence.
    Gynecologic Oncology 01/2014; · 3.93 Impact Factor
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    ABSTRACT: Contribution over time of human papillomavirus (HPV) types in human cancers has been poorly documented. Such data is fundamental to measure current HPV vaccines impact in the years to come. We estimated the HPV type-specific distribution in a large international series of invasive cervical cancer (ICC) over 70 years prior to vaccination. Paraffin embedded ICC cases diagnosed between 1940 and 2007 were retrieved from eleven countries in Central-South America, Asia and Europe. Included countries reported to have low-medium cervical cancer screening uptake. Information on age at and year of diagnosis was collected from medical records. After histological confirmation, HPV DNA detection was performed by SPF-10/DEIA/LiPA25 (version1). Logistic regression models were used for estimating the adjusted relative contributions (RC) of HPV16 and of HPV18 over time. Among 4,771 HPV DNA positive ICC cases, HPV16 and HPV18 were the two most common HPVs in all the decades with no statistically significant variations of their adjusted-RC from 1940–59 to 2000–07 (HPV16—from 61.5 to 62.1%, and HPV18—from 6.9 to 7.2%). As well, the RC of other HPV types did not varied over time. In the stratified analysis by histology, HPV16 adjusted-RC significantly increased across decades in adenocarcinomas. Regarding age, cases associated to either HPV16, 18 or 45 were younger than those with other HPV types in all the evaluated decades. The observed stability on the HPV type distribution predicts a high and stable impact of HPV vaccination in reducing the cervical cancer burden in future vaccinated generations.
    International Journal of Cancer 12/2013; · 6.20 Impact Factor
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    ABSTRACT: Background Anal intraepithelial neoplasia (AIN) is present in the majority of HIV+ men who have sex with men (MSM). The main aetiological factor is human papilloma virus (HPV). We analysed whether HPV PCR genotyping of whole tissue sections (WTS) and subsequent laser capture microdissection (LCM) detects type-specific HPV DNA in individual areas of HGAIN, and compared these lesional HPV genotypes with HPV types in anal swabs. Methods: DNA was isolated from anal swabs and WTS of 31 HGAIN biopsies obtained from 21 HIV+ MSM and analysed by the SPF10 PCR/LiPA25 HPV genotyping system. In case of multiple HPV types per WTS, PCR was repeated in selected areas of AIN obtained by LCM. Results: A single HPV type was observed in 15 (48%) of 31 WTS. In the 16 WTS with multiple HPV types, LCM-isolated dysplastic areas were studied. In 14 of the 16 WTS, one single HPV type was demonstrated within each discrete area of the lesion, resulting in a total of 29 (15+14) biopsies in which a single HPV type was found in (all components of) the lesion. HPV 16 was found in 14 of 31 biopsies (45%). In almost half the biopsies, lesional HPV types were not detected in the anal swabs. Conclusions: WTS PCR and subsequent LCM PCR is accurate in detecting lesion-specific HPV types in HGAIN and in 94% of the biopsies a single HPV was found in (each component of) the HGAIN lesion. In the majority, HPV16 was not the causative type and HPV genotyping of anal swabs was not useful in detecting the lesion-specific type.
    Sexual Health 11/2013; 10(6):586-587. · 1.65 Impact Factor
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    ABSTRACT: The Costa Rica HPV16/18 Vaccine Trial (CVT) showed that four-year vaccine efficacy against 12-month HPV16/18 persistent infection was similarly high among women who received one, two, or the recommended three doses of the bivalent HPV16/18 L1 virus-like particle (VLP) vaccine. Live-attenuated viral vaccines, but not simple-subunit vaccines, usually induce durable lifelong antibody responses after a single dose. It is unclear whether noninfectious VLP vaccines behave more like live-virus or simple-subunit vaccines in this regard. To explore the likelihood that efficacy will persist longer term, we investigated the magnitude and durability of antibodies to this vaccine by measuring HPV16- and HPV18-specific antibodies by VLP-ELISA using serum from enrollment, vaccination, and annual visits through four years in four vaccinated groups; one-dose (n = 78), two-doses separated by one month (n = 140), two doses separated by six months (n = 52), and three scheduled doses (n = 120, randomly selected). We also tested enrollment sera from n = 113 HPV16- or HPV18 L1-seropositive women prevaccination, presumably from natural infection. At four years, 100% of women in all groups remained HPV16/18 seropositive; both HPV16/18 geometric mean titers (GMT) among the extended two-dose group were non-inferior to the three-dose group, and ELISA titers were highly correlated with neutralization titers in all groups. Compared with the natural infection group, HPV16/18 GMTs were, respectively, at least 24 and 14 times higher among the two-dose and 9 and 5 times higher among one-dose vaccinees. Antibody levels following one-dose remained stable from month 6 through month 48. Results raise the possibility that even a single dose of HPV VLPs will induce long-term protection. Cancer Prev Res; 6(11); 1242-50. ©2013 AACR.
    Cancer Prevention Research 11/2013; 6(11):1242-50. · 4.89 Impact Factor
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    ABSTRACT: Poorer survival from head and neck squamous cell carcinoma (HNSCC) in African Americans (AA) may be due to disparity in the prevalence of Human Papillomavirus (HPV) but earlier studies often failed to control other etiological factors. We aimed to elucidate whether racial disparities in HPV prevalence and overall survival were due to confounding from smoking or alcohol use. 385 patients with SCC of the mouth, pharynx, nose, or larynx who had surgical resection at Wayne State University affiliated hospitals were identified through a population-based cancer registry. Formalin fixed paraffin embedded tissue blocks were used to determine the presence of HPV DNA and its genotype using a sensitive broad-spectrum PCR technique. Patients' demographics, tumor characteristics and vital status were obtained through record linkage with the registry data and smoking and alcohol information was abstracted from medical record. Cox's proportional hazard model and unconditional logistic regression models were employed to analyze the overall survival and tumor HPV-positivity, respectively. HPV positivity in oropharyngeal cancer was substantially lower in AA than in other racial groups (odds ratio 0.14, 95% confidence interval (CI) 0.05-0.37) and adjustment for smoking or alcohol did not change this association. However, a significantly increased hazard ratio of death in AA oropharyngeal cancer patients (univariable hazard ratio (HR) 2.55, 95% CI 1.42-4.59) decreased to almost unity (HR 1.49, 95% CI 0.75-2.93) after adjustment for HPV and smoking. Lower HPV prevalence in AA largely accounts for their poorer survival from oropharyngeal cancer, but not other HNSSC.
    American journal of otolaryngology 09/2013; · 0.77 Impact Factor
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    ABSTRACT: Background. Little is known about the epidemiology of oral human papillomavirus (HPV) in Latin America.Methods. Women (N = 5838) aged 22-29 in the control and vaccine arms of an HPV-16/18 vaccine trial in Costa Rica had oral, cervical, and anal specimens collected. Samples were tested for alpha mucosal HPV types (SPF10/LiPA25 version 1); a subset of oral samples (n = 500) was tested for cutaneous HPV types in the genera alpha, beta, gamma, mu, and nu.Results. In the control arm (n = 2926), 1.9% of women had an oral alpha mucosal HPV detected, 1.3% had carcinogenic HPV, and 0.4% had HPV-16; similar patterns for non-16/18 HPV types were observed in the vaccine arm. Independent risk factors for any oral alpha mucosal HPV among women in the control arm included marital status (adjusted odds ratio [AOR], 3.2; 95% confidence interval [CI], 1.8-5.7 for single compared to married/living as married), number of sexual partners (AOR, 2.4; 95% CI, 1.0-6.1 for ≥4 partners compared to 0-1 partners), chronic sinusitis (AOR, 3.1; 95% CI, 1.5-6.7), and cervical HPV infection (AOR, 2.6; 95% CI, 1.4-4.6). Detection of beta HPV was common (18.6%) and not associated with sexual activity.Conclusions. Unlike cutaneous HPV types, alpha mucosal HPV types were uncommon in the oral region and were predominately associated with sexual behavior.Clinical Trials Registration. NCT00128661.
    The Journal of Infectious Diseases 09/2013; · 5.85 Impact Factor
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    ABSTRACT: Low-risk human papillomaviruses (LR-HPVs) have been associated occasionally with clinically and pathologically unusual anogenital malignancies. The relation between clinicopathologic features and any pathogenetic role of LR-HPV remains unclear. From a global study of 13,328 anogenital carcinomas, we identified 57 cases in which whole-tissue polymerase chain reaction using SPF10-LiPA25 showed single LR-HPV infection. In 43/46 (93.5%) available carcinomas, multiple polymerase chain reaction assays confirmed single detection of HPV6, 11, 42, 44, or 70 DNA. In 75% (n=32) of these, LR-HPV DNA was confirmed in tumor cells by laser capture microdissection. In 2 cases, including 1 adenocarcinoma, viral DNA was only found outside the tumor. All anogenital tumors with confirmed HPV6/11 showed a distinctive range of papillary, warty or warty-basaloid, squamous, or transitional histology with patchy or negative p16 expression. HPV6-associated cervical tumors occurred at a low median age. HPV42/70 was associated with typical squamous cell carcinoma showing diffuse p16 staining like high-risk HPV-related malignancies. HPV44 was found in malignant cells in 1 case. Viral taxonomy and theoretical analysis show that HPV6/11 belong to a different genus from HPV42/70 with E6/E7 gene products that would not bind pRb or p53, whereas HPV42/70 could bind pRb. Our data support the causal involvement of LR-HPVs in the carcinogenesis of <2% of anogenital malignancies of 2 distinct clinicopathologic patterns related to the genetic structure of the HPV types 6/11 and 70/42. HPV42/70 was associated with typical squamous carcinomas. Importantly all carcinomas associated with HPV6/11 globally showed verruco-papillary, well-differentiated, squamous, or transitional histology without p16 expression.
    The American journal of surgical pathology 09/2013; 37(9):1299-310. · 4.06 Impact Factor
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    ABSTRACT: Most cervical cancers are attributable to infection with one of fourteen types of human papillomavirus (HPV), but HPV types differ in oncogenic potential. Characterisation of cancers associated with specific HPV types is required to predict the likely impact of current prophylactic vaccines and the potential benefits of vaccine formulations including additional HPV types. The study aimed to correlate HPV type with histology and age at diagnosis, in Invasive Cervical Cancers (ICCs) from two of the devolved countries of the UK (Wales and Scotland). Centralised histopathology review and rigorously standardised HPV-DNA typing were applied to 592 ICC diagnosed 2001-2006. HPV status was analysed in relation to histology and age at diagnosis. HPV infection was confirmed in 535/592 cases. Among the 497 tumours infected with single HPV types, the three most common types were HPV16 (62% 95%CI: 57.6-66.1), HPV18 (18.9% 95%CI: 15.7-22.6) and HPV45 (5.4% 95%CI: 3.7-7.8). HPV16 or 18 were present in 80.9% of HPV positive cases. Women with tumours associated with HPV types 16, 18 and 45 were on average 10.5 years younger at diagnosis than women with tumours associated with other HPV types. Prophylactic vaccines targeting HPV16 and 18 could potentially prevent up to 80.9% of ICC in the populations investigated. Cancers associated with HPV16, 18 and 45 were diagnosed at younger ages, supporting the hypothesis of faster progression than for tumours caused by other HPV types.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 08/2013; · 3.12 Impact Factor
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    ABSTRACT: In sub-Saharan Africa, invasive cervical cancer (ICC) incidence and mortality are among the highest in the world. This cross-sectional epidemiological study assessed human papillomavirus (HPV) prevalence and type distribution in women with ICC in Ghana, Nigeria, and South Africa. Cervical biopsy specimens were obtained from women aged ≥21 years with lesions clinically suggestive of ICC. Histopathological diagnosis of ICC was determined by light microscopy examination of hematoxylin and eosin stained sections of paraffin-embedded cervical specimens; samples with a confirmed histopathological diagnosis underwent HPV DNA testing by polymerase chain reaction. HPV-positive specimens were typed by reverse hybridization line probe assay. Between October 2007 and March 2010, cervical specimens from 659 women were collected (167 in Ghana, 192 in Nigeria, and 300 in South Africa); 570 cases were histologically confirmed as ICC. The tumor type was identified in 551/570 women with ICC; squamous cell carcinoma was observed in 476/570 (83.5%) cases. The HPV-positivity rate in ICC cases was 90.4% (515/570). In ICC cases with single HPV infection (447/515 [86.8%]), the most commonly detected HPV types were HPV16 (51.2%), HPV18 (17.2%), HPV35 (8.7%), HPV45 (7.4%), HPV33 (4.0%), and HPV52 (2.2%). The prevalence of single and multiple HPV infections seemed higher among HIV-positive women and HPV type distribution appeared to differ according to tumor type and HIV status. In conclusion, HPV16, 18, 45, and 35 were the most common HPV types in sub-Saharan African women with ICC and HPV infections were more common in HIV-positive women © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 08/2013; · 6.20 Impact Factor
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    ABSTRACT: It has been reported that approximately 10% of low grade squamous intraepithelial lesions (LSIL) progress to high grade squamous intraepithelial lesions (HSIL) within a 2-year follow up. The factors related to lesion progression are currently unknown. The aim of the study was to identify prognostic markers of the course of LSIL. This retrospective study was designed to correlate regression, persistence and progression of biopsy-proven LSIL with patients' age, HPV genotypes and immunohistochemical expression of the main cell cycle regulating proteins: p53, pRb, p16, and Ki-67. A total of 584 consecutive patients with biopsy proven LSIL and 2-year follow-up were included in the age analysis. HPV genotyping was performed in 328 LSIL cases using the SPF10 PCR-LiPA25 (version 1), 238 LSIL cases were immunostained for Ki-67 and p16, and 101 cases were immunostained for pRb and p53. The odds of LSIL persistence and progression were significantly higher in women 30-39, 40-49 and 50+ years old, as compared to women 20-29 years old (OR 1.89, 2.52 and 2.39, respectively). The odds of persistence and progression were higher in women infected with HPV16, 18, 33 and 52 (OR 3.5, 3.1, 3.5 and 2.9, respectively). There were no significant differences in expression of immunomarkers (p16, p53, pRB and Ki-67) between the lesions that regressed versus the lesions that persisted or progressed. Patients 30 years of age and older have a higher risk of LSIL progression or persistence as compared to 20-29 year olds. In addition, HPV genotyping, but not the cell cycle markers, may aid in prognosis of LSIL course.
    European journal of obstetrics, gynecology, and reproductive biology 08/2013; · 1.97 Impact Factor
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    ABSTRACT: Human papillomavirus (HPV) contribution in vulvar intraepithelial lesions (VIN) and invasive vulvar cancer (IVC) is not clearly established. This study provides novel data on HPV markers in a large series of VIN and IVC lesions. Histologically confirmed VIN and IVC from 39 countries were assembled at the Catalan Institute of Oncology (ICO). HPV-DNA detection was done by polymerase chain reaction using SPF-10 broad-spectrum primers and genotyping by reverse hybridisation line probe assay (LiPA25) (version 1). IVC cases were tested for p16(INK4a) by immunohistochemistry (CINtec histology kit, ROCHE). An IVC was considered HPV driven if both HPV-DNA and p16(INK4a) overexpression were observed simultaneously. Data analyses included algorithms allocating multiple infections to calculate type-specific contribution and logistic regression models to estimate adjusted prevalence (AP) and its 95% confidence intervals (CI). Of 2296 cases, 587 were VIN and 1709 IVC. HPV-DNA was detected in 86.7% and 28.6% of the cases respectively. Amongst IVC cases, 25.1% were both HPV-DNA and p16(INK4a) positive. IVC cases were largely keratinising squamous cell carcinoma (KSCC) (N=1234). Overall prevalence of HPV related IVC cases was highest in younger women for any histological subtype. SCC with warty or basaloid features (SCC_WB) (N=326) were more likely to be HPV and p16(INK4a) positive (AP=69.5%, CI=63.6-74.8) versus KSCC (AP=11.5%, CI=9.7-13.5). HPV 16 was the commonest type (72.5%) followed by HPV 33 (6.5%) and HPV 18 (4.6%). Enrichment from VIN to IVC was significantly high for HPV 45 (8.5-fold). Combined data from HPV-DNA and p16(INK4a) testing are likely to represent a closer estimate of the real fraction of IVC induced by HPV. Our results indicate that HPV contribution in invasive vulvar cancer has probably been overestimated. HPV 16 remains the major player worldwide.
    European journal of cancer (Oxford, England: 1990) 07/2013; · 4.12 Impact Factor
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    ABSTRACT: High risk human papillomaviruses (HR-HPV) are known to be extremely common, sexually transmitted infections, but more information is needed regarding the absolute risks of type-specific HR-HPV infections in the years following sexual debut. We conducted a survival analysis of 3,737 women aged 18--25 from the control group of the Costa Rican Vaccine trial to determine the absolute risks of HR-HPV infections at 12 months, 24 months, and end of follow-up (average of 50.7 months). To corroborate determinants of infection, we used Cox proportional hazards methods to assess associations between demographics and sexual risk behaviors and incident HR-HPV. Cumulative incidence for HR-HPV infections was 51.3% at the end of the study period. The most common incident types were HPV52 (15.4%), HPV51 (13.6%), and HPV16 (12.4%). Type-specific cumulative incidence corresponded closely with type-specific prevalences, except that HPV16 was more prevalent than predicted by incidence, suggesting greater persistence. The strongest predictors of incident HR-HPV infections as a group in a multivariate analysis were the expected correlates of sexual behavior of the woman and her partner, such as being single (HR 1.6, 95% CI 1.4-1.8) or divorced/widowed (HR: 2.1, 95% CI: 1.7-2.7), having multiple HPV infections at enrollment (HR: 1.5, 95% CI: 1.3-1.7), and current smoking (HR: 1.2, 95% CI: 1.0-1.3). In women who reported being having only one lifetime sexual partner (being in a monogamous relationship), the strongest predictors of HR-HPV included not living with sex partner (HR: 2.1, 95% CI 1.7-2.5) and age of sex partner (HR: 1.4, 95% CI: 1.0-1.8). We confirm the extremely high incidence of HR-HPV in young women, emphasizing the importance of vaccinating young girls before sexual debut.
    BMC Infectious Diseases 07/2013; 13(1):308. · 3.03 Impact Factor
  • PLoS ONE 07/2013; 8(7):68329-. · 3.73 Impact Factor

Publication Stats

11k Citations
1,551.24 Total Impact Points

Institutions

  • 1995–2014
    • DDL Diagnostic Laboratory
      Rijswijk, South Holland, Netherlands
  • 2013
    • Catalan Institute of Oncology
      Badalona, Catalonia, Spain
  • 2008–2013
    • National Cancer Institute (USA)
      • • Division of Cancer Epidemiology and Genetics
      • • Infections and Immunoepidemiology
      Bethesda, MD, United States
    • Johns Hopkins University
      Baltimore, Maryland, United States
    • Makerere University
      • Department of Pathology
      Kampala, Kampala District, Uganda
    • Johns Hopkins Bloomberg School of Public Health
      • Department of Epidemiology
      Baltimore, Maryland, United States
  • 2003–2013
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Academic Medical Center
      Amsterdamo, North Holland, Netherlands
    • Emory University
      Atlanta, Georgia, United States
  • 2012
    • Universidad Nacional de Asunción
      San Lorenzo del Campo Grande, Central, Paraguay
  • 2003–2012
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands
  • 2011
    • Costa Rican Institute for Research and Education on Nutrition and Health
      La Unión, Cartago, Costa Rica
    • Secretariat of Health, Sao Paulo
      San Paulo, São Paulo, Brazil
    • University of Antioquia
      Santa Fe de Antioquia, Antioquia, Colombia
  • 2010–2011
    • Karolinska Institutet
      • Institutionen för medicinsk epidemiologi och biostatistik
      Solna, Stockholm, Sweden
    • Istituto Regina Elena - Istituti Fisioterapici Ospitalieri
      Roma, Latium, Italy
  • 2007–2011
    • National Institutes of Health
      • • Branch of Infections and Immunoepidemiology
      • • Division of Cancer Epidemiology and Genetics
      • • Branch of Hormonal and Reproductive Epidemiology
      Bethesda, MD, United States
    • University of Helsinki
      • Department of Obstetrics and Gynaecology
      Helsinki, Province of Southern Finland, Finland
    • Università di Pisa
      Pisa, Tuscany, Italy
  • 2006–2011
    • Leiden University Medical Centre
      • • Department of Public Health and Primary care
      • • Department of Medical Microbiology
      Leyden, South Holland, Netherlands
    • University of New Mexico
      • Department of Molecular Genetics/Microbiology
      Albuquerque, NM, United States
  • 1998–2011
    • University of Amsterdam
      • • Department of Obstetrics and Gynaecology
      • • Department of Gastroenterology and Hepatology
      Amsterdam, North Holland, Netherlands
  • 1984–2011
    • Radboud University Nijmegen
      • • Department of Obstetrics and Gynecology
      • • Department of Medical Microbiology
      • • Department of Biochemistry
      Nijmegen, Provincie Gelderland, Netherlands
  • 2009
    • National Institute for Biological Standards and Control
      • Division of Virology
      Potters Bar, ENG, United Kingdom
    • VU University Medical Center
      • Department of Pathology
      Amsterdam, North Holland, Netherlands
  • 1997–2005
    • Slotervaartziekenhuis
      Amsterdamo, North Holland, Netherlands
    • St Anna Ziekenhuis
      Гельдроп, North Brabant, Netherlands
  • 2004
    • National Cancer Center Korea
      Kōyō, Gyeonggi Province, South Korea
    • Geisel School of Medicine at Dartmouth
      • Department of Obstetrics and Gynecology
      Hanover, New Hampshire, United States
  • 1999–2004
    • Reinier de Graaf Groep
      Delft, South Holland, Netherlands
    • Ghent University
      • Faculty of Veterinary Medicine
      Gent, VLG, Belgium
  • 2002
    • University of São Paulo
      • Faculty of Medicine (FM)
      São Paulo, Estado de Sao Paulo, Brazil
  • 2001
    • Centre Hospitalier Universitaire Mont-Godinne
      Yvoir, Walloon Region, Belgium
  • 1998–1999
    • University of Porto
      Oporto, Porto, Portugal
  • 1990–1997
    • Erasmus Universiteit Rotterdam
      • • Department of Dermatology
      • • Department of Virology
      Rotterdam, South Holland, Netherlands
  • 1996
    • Het Oogziekenhuis Rotterdam
      Rotterdam, South Holland, Netherlands
  • 1994–1996
    • University of Antwerp
      Antwerpen, Flanders, Belgium
    • Centraalbureau voor Schimmelcultures
      Utrecht, Utrecht, Netherlands
  • 1993–1996
    • University of Groningen
      • Department of Obstetrics and Gynaecology
      Groningen, Province of Groningen, Netherlands
    • Université Libre de Bruxelles
      • Laboratory of Microbiology
      Brussels, BRU, Belgium
  • 1992–1994
    • Gezond Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 1988
    • Netherlands Cancer Institute
      • Division of Molecular Genetics
      Amsterdam, North Holland, Netherlands