RESUMO
OBJECTIVES: The aim was to evaluate the cross-sectional and long-term triage performance of FAM19A4/miR124-2 methylation analysis in human papillomavirus (HPV)-based cervical screening. METHODS: We conducted a post hoc analysis within a Dutch population-based HPV-positive study cohort of women aged 30-60 years (n = 979). Cross-sectional cervical intraepithelial neoplasia (CIN) 3+ sensitivity, specificity, positive predictive value and negative predictive value as well as cumulative CIN3+ or cervical cancer risks after 9 and 14 years were compared for three baseline triage strategies: (1) cytology, (2) FAM19A4/miR124-2 methylation analysis and (3) combined FAM19A4/miR124-2 methylation with cytology. RESULTS: CIN3+ sensitivity of FAM19A4/miR124-2 methylation analysis was similar to that of cytology (71.3% vs 76.0%, ratio 0.94, 95% CI 0.84 to 1.05), at a lower specificity (78.3% vs 87.0%, ratio 0.90, 95% CI 0.86 to 0.94). Combining FAM19A4/miR124-2 methylation analysis with cytology resulted in a CIN3+ sensitivity of 84.6% (95% CI 78.3 to 90.8) at a specificity of 69.6% (95% CI 66.5 to 72.7). Similar 9- and 14-year CIN3+ risks for baseline cytology-negative women and baseline FAM19A4/miR124-2 methylation-negative women were observed, with risk differences of -0.42% (95% CI -2.1 to 1.4) and -0.07% (95% CI -1.9 to 1.9), respectively. The 14-year cumulative cervical cancer incidence was significantly lower for methylation-negative women compared to cytology-negative women (risk difference 0.98%, 95% CI 0.26 to 2.0). DISCUSSION: FAM19A4/miR124-2 methylation analysis has a good triage performance on baseline screening samples, with a cross-sectional CIN3+ sensitivity and long-term triage-negative CIN3+ risk equalling cytology triage. Therefore, FAM19A4/miR124-2 methylation analysis appears to be a good and objective alternative to cytology in triage scenarios in HPV-based cervical screening.
Assuntos
Citocinas/genética , Infecções por Papillomavirus/diagnóstico , Triagem/métodos , Adulto , Biomarcadores Tumorais/genética , Estudos Transversais , Metilação de DNA , Detecção Precoce de Câncer , Feminino , Humanos , Estudos Longitudinais , Programas de Rastreamento , MicroRNAs/genética , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Papillomaviridae , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/genéticaRESUMO
BACKGROUND: Persistent high-risk human papillomavirus (HPV) infection is endorsed by the World Health Organization as an intermediate endpoint for evaluating HPV vaccine effectiveness/efficacy. There are different approaches to estimate the vaccine effectiveness/efficacy against persistent HPV infections. METHODS: We performed a systematic literature search in Pubmed to identify statistical approaches that have been used to estimate the vaccine effectiveness/efficacy against persistent HPV infections. We applied these methods to data of a longitudinal observational study to assess their performance and compare the obtained vaccine effectiveness (VE) estimates. RESULTS: Our literature search identified four approaches: the conditional exact test for comparing two independent Poisson rates using a binomial distribution, Generalized Estimating Equations for Poisson regression, Prentice Williams and Peterson total time (PWP-TT) and Cox proportional hazards regression. These approaches differ regarding underlying assumptions and provide different effect measures. However, they provided similar effectiveness estimates against HPV16/18 and HPV31/33/45 persistent infections in a cohort of young women eligible for routine HPV vaccination (range VE 93.7-95.1% and 60.4-67.7%, respectively) and seemed robust to violations of underlying assumptions. CONCLUSIONS: As the rate of subsequent infections increased in our observational cohort, we recommend PWP-TT as the optimal approach to estimate the vaccine effectiveness against persistent HPV infections in young women. Confirmation of our findings should be undertaken by applying these methods after longer follow-up in our study, as well as in different populations.
Assuntos
Papillomavirus Humano 18/imunologia , Papillomavirus Humano 31/imunologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Vacinas contra Papillomavirus/uso terapêutico , Vacinação , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Imunogenicidade da Vacina , Estudos Longitudinais , Infecções por Papillomavirus/virologia , Prevalência , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: Because current guidelines recognise high-grade anal squamous intraepithelial lesions (HSILs) and low-grade SILs (LSILs), and recommend treatment of all HSILs although not all progress to cancer, this study aims to distinguish transforming and productive HSILs by grading immunohistochemical (IHC) biomarkers p16INK 4a (p16) and E4 in low-risk human papillomavirus (lrHPV) and high-risk (hr)HPV-associated SILs as a potential basis for more selective treatment. METHODS: Immunostaining for p16 and HPV E4 was performed and graded in 183 biopsies from 108 HIV-positive men who have sex with men. The causative HPV genotype of the worst lesion was identified using the HPV SPF10-PCR-DEIA-LiPA25 version 1 system, with laser capture microdissection for multiple infections. The worst lesions were scored for p16 (0-4) to identify activity of the hrHPV E7 gene, and panHPV E4 (0-2) to mark HPV production and life cycle completion. RESULTS: There were 37 normal biopsies, 60 LSILs and 86 HSILs, with 85% of LSILs caused by lrHPV and 93% of HSILs by hrHPV. No normal biopsy showed E4, but 43% of LSILs and 37% of HSILs were E4 positive. No differences in E4 positivity rates were found between lrHPV and hrHPV lesions. Most of the lesions caused by lrHPV (90%) showed very extensive patchy p16 staining; p16 grade in HSILs was variable, with frequency of productive HPV infection dropping with increasing p16 grade. CONCLUSIONS: Combined p16/E4 IHC identifies productive and nonproductive HSILs associated with hrHPV within the group of HSILs defined by the Lower Anogenital Squamous Terminology recommendations. This opens the possibility of investigating selective treatment of advanced transforming HSILs caused by hrHPV, and a 'wait and see' policy for productive HSILs. What's already known about this topic? For preventing anal cancer in high-risk populations, all patients with high-grade squamous intraepithelial lesions (HSILs) are treated, even though this group of lesions is heterogeneous, the histology is variable and regression is frequent. What does this study add? By adding human papillomavirus (HPV) E4 immunohistochemistry to p16 INK4a (p16), and grading expression of both markers, different biomarker expression patterns that reflect the heterogeneity of HSILs can be identified. Moreover, p16/E4 staining can separate high-risk HPV-associated HSILs into productive and more advanced transforming lesions, providing a potential basis for selective treatment.
Assuntos
Alphapapillomavirus , Infecções por Papillomavirus , Minorias Sexuais e de Gênero , Lesões Intraepiteliais Escamosas , Biomarcadores Tumorais , Inibidor p16 de Quinase Dependente de Ciclina , Homossexualidade Masculina , Humanos , Masculino , Papillomaviridae/genética , Infecções por Papillomavirus/complicaçõesRESUMO
Based on scientific data showing that HPV testing provides better protection against cervical precancer and cancer than cytology, in 2011 the Dutch Health Council advised the Minister of Welfare, Health and Sports to replace cytology by HPV testing in the Dutch population-based screening programme. After a successful evaluation of the feasibility of HPV-based screening in 2014, primary HPV testing for cervical screening was implemented in 2017. The Netherlands has been one of the first countries worldwide to implement nationwide HPV-based screening and its experience with the new programme is therefore followed with great interest. In this manuscript, we present an overview of the studies that were instrumental in the choice of HPV assay and triage strategy, the adjustment of screening starting and exit ages and intervals, and the implementation of HPV self-sampling. Finally, we review the cost-effectiveness of the proposed new screening algorithm and we explore future perspectives. The rationale behind the new Dutch HPV-based screening programme, which is based on risk management, could serve as a guidance to other countries that are planning to implement HPV-based screening in the near future.
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Detecção Precoce de Câncer , Programas de Rastreamento , Infecções por Papillomavirus/diagnóstico , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Análise Custo-Benefício , Feminino , Humanos , Países Baixos , Papillomaviridae/isolamento & purificação , GravidezRESUMO
Background: Monitoring vaccine effectiveness (VE) in vaccination programs is of importance for assessing the impact of immunization. This study aimed to estimate the VE of the bivalent human papillomavirus (HPV) vaccine against incident and 12-month persistent infections up to 6 years after vaccination. Methods: In 2009-2010, girls eligible for the vaccination catch-up campaign (ie, those aged 14-16 years) were enrolled into a prospective cohort. Annually, participants completed a questionnaire and submitted a self-collected vaginal swab sample for HPV testing by the SPF10-LiPA25 assay. We compared sociodemographic characteristics and infection rates between vaccinated and unvaccinated girls. The VE was adjusted for characteristics related to HPV vaccination status. We used combined end points for VE estimation. Results: In total, 1635 women, of whom 54% were fully vaccinated, were included for VE estimation. The adjusted VE against HPV16 and 18 persistent infections amounted to 97.7% (95% confidence interval [CI], 83.5%-99.7%). We found a VE against HPV31, 33, and 45 persistent infections of 61.8% (95% CI, 16.7%-82.5%). We found no indications that the protection against vaccine or cross-protective types changes over time. Conclusion: Our findings of nearly full protection against vaccine-type persistent infections and significant cross-protection to nonvaccine types in a population-based cohort study confirm the effectiveness of the bivalent HPV vaccine as estimated in trials. We found no indications for waning protection up to 6 years after vaccination.
Assuntos
Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Adolescente , Adulto , Proteção Cruzada/imunologia , Feminino , Humanos , Programas de Imunização/métodos , Estudos Prospectivos , Vacinação/métodos , Vagina/virologia , Adulto JovemRESUMO
Human papillomavirus (HPV) testing is increasingly being incorporated into cervical cancer screening. The Validation of HPV Genotyping Tests (VALGENT) is a framework designed to evaluate the clinical performance of various HPV tests relative to that of the validated and accepted comparator test in a formalized and uniform manner. The aim of this study was to evaluate the clinical performance of the HPV-Risk assay with samples from the VALGENT-3 panel and to compare its performance to that of the clinically validated Hybrid Capture 2 assay (HC2). The VALGENT-3 panel comprises 1,300 consecutive samples from women participating in routine cervical cancer screening and is enriched with 300 samples from women with abnormal cytology. DNA was extracted from original ThinPrep PreservCyt medium aliquots, and HPV testing was performed using the HPV-Risk assay by investigators blind to the clinical data. HPV prevalence was analyzed, and the clinical performance of the HPV-Risk assay for the detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) and CIN2 or worse (CIN2+) relative to the performance of HC2 was assessed. The sensitivity of the HPV-Risk assay for the detection of CIN3+ was similar to that of HC2 (relative sensitivity, 1.00; 95% confidence interval [CI], 0.95 to 1.05; P = 1.000), but the specificity of the HPV-Risk assay was significantly higher than that of HC2 (relative specificity, 1.02; 95% CI, 1.01 to 1.04; P < 0.001). For the detection of CIN2+, similar results were obtained, with the relative sensitivity being 0.98 (95% CI, 0.93 to 1.02; P = 0.257) and the relative specificity being 1.02 (95% CI, 1.01 to 1.03; P < 0.001). The performance of the HPV-Risk assay for the detection of CIN3+ and CIN2+ was noninferior to that of HC2, with all P values being ≤0.006. In conclusion, the HPV-Risk assay demonstrated noninferiority to the clinically validated HC2 by the use of samples from the VALGENT-3 panel for test validation and comparison.
Assuntos
Detecção Precoce de Câncer/métodos , Técnicas de Genotipagem/métodos , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Adulto JovemRESUMO
BACKGROUND: Cannabis exposure, particularly heavy cannabis use, has been associated with neuroanatomical alterations in regions rich with cannabinoid receptors such as the hippocampus in some but not in other (mainly cross-sectional) studies. However, it remains unclear whether continued heavy cannabis use alters hippocampal volume, and whether an earlier age of onset and/or a higher dosage exacerbate these changes. METHODS: Twenty heavy cannabis users (mean age 21 years, range 18-24 years) and 23 matched non-cannabis using healthy controls were submitted to a comprehensive psychological assessment and magnetic resonance imaging scan at baseline and at follow-up (average of 39 months post-baseline; standard deviation=2.4). Cannabis users started smoking around 16 years and smoked on average five days per week. A novel aspect of the current study is that hippocampal volume estimates were obtained from manual tracing the hippocampus on T1-weighted anatomical magnetic resonance imaging scans, using a previously validated protocol. RESULTS: Compared to controls, cannabis users did not show hippocampal volume alterations at either baseline or follow-up. Hippocampal volumes increased over time in both cannabis users and controls, following similar trajectories of increase. Cannabis dose and age of onset of cannabis use did not affect hippocampal volumes. CONCLUSIONS: Continued heavy cannabis use did not affect hippocampal neuroanatomical changes in early adulthood. This contrasts with prior evidence on alterations in this region in samples of older adult cannabis users. In young adults using cannabis at this level, cannabis use may not be heavy enough to affect hippocampal neuroanatomy.
Assuntos
Hipocampo/patologia , Fumar Maconha/patologia , Adolescente , Estudos de Casos e Controles , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Adulto JovemRESUMO
INTRODUCTION: Recent studies have shown that CADM1/MAL-methylation testing detects high-grade CIN lesions with a high short-term progression risk for cervical cancer. Women treated for CIN2/3 are at risk of post-treatment disease, representing either persistent (incompletely treated) or incident (early onset) lesions. Here, we evaluated CADM1/MAL-methylation analysis as potential tool for detecting recurrent high-grade CIN lesions (rCIN2/3). METHODS AND MATERIALS: A multicenter prospective clinical cohort study was conducted among 364 women treated for CIN2/3. Cervical scrapes were taken prior to treatment, and six and 12months post-treatment and tested for cytology, hrHPV (plus genotype) and CADM1/MAL-methylation. When at six months either of these tests was positive, a colposcopy-directed biopsy was obtained. At 12months, all women underwent an exit-colposcopy with biopsy. In case of rCIN2/3, re-treatment was done. RESULTS: We found 28 rCIN2 (7.7%) and 14 rCIN3 (3.8%), resulting in a total recurrence rate of 11.5%. All 14 women with rCIN3 and 15/28 (54%) with rCIN2 showed hrHPV type-persistence. Of these, 9/14 (64%) rCIN3 and 8/15 (53%) rCIN2 were CADM1/MAL-methylation positive. All incident rCIN2, characterized by hrHPV genotype-switch, were CADM1/MAL-methylation negative. All three carcinomas found after re-treatment were CADM1/MAL-methylation positive. CADM1/MAL-methylation positivity at both baseline and follow-up significantly increased the risk of ≥rCIN3 (from 0.7% to 18.4%), and ≥rCIN2 (from 8.2% to 36.8%), compared to a consistently CADM1/MAL-methylation negative result (p-value: <0.001). CONCLUSION: Post-treatment monitoring by CADM1/MAL-methylation analysis identifies women with an increased risk of rCIN2/3. Our results confirm previous data indicating that CADM1/MAL-methylation analysis provides a high reassurance against cancer.
Assuntos
Moléculas de Adesão Celular/genética , Metilação de DNA , Imunoglobulinas/genética , Proteínas Proteolipídicas Associadas a Linfócitos e Mielina/genética , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , Adulto , Molécula 1 de Adesão Celular , Feminino , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVE: Obsessive-compulsive symptoms (OCS) frequently occur in psychotic disorders. Cross-sectional associations between OCS and cognitive impairment have led to different causal explanations. Whereas one assumes that higher cognitive impairment reflects a risk factor for psychotic patients to develop OCS, another suggests that deficits reflect a consequence of OCS. This study investigated the longitudinal interrelation between OCS and cognitive functioning. METHOD: Baseline and follow-up data from 622 patients and 670 un-affected siblings from the 'Genetic Risk and Outcome in Psychosis' study were analyzed. Participants were allocated to groups according to the presence or absence of OCS at assessments and compared on several cognitive domains. RESULTS: Cross-sectional comparisons revealed no group differences in cognitive performance. Longitudinal analyses comparing the groups with changes in OCS revealed one significant group effect with more problems in set-shifting abilities in patient who reported OCS development at follow-up. Significant time and interaction effects were mainly due to improvement in immediate verbal recall and digit-symbol coding in patients and siblings who reported remission of OCS. CONCLUSION: Although insight into causality needs further exploration, our results do not confirm the hypothesis of pre-existing cognitive risk constellations. Findings suggest that remission of comorbid OCS results in improved immediate verbal recall and processing speed.
Assuntos
Transtornos Cognitivos/fisiopatologia , Função Executiva/fisiologia , Rememoração Mental/fisiologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Desempenho Psicomotor/fisiologia , Transtornos Psicóticos/fisiopatologia , Adolescente , Adulto , Transtornos Cognitivos/epidemiologia , Comorbidade , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtornos Psicóticos/epidemiologia , Irmãos , Adulto JovemRESUMO
OBJECTIVE. A previous study has shown that Dynamic Spectral Imaging (DSI) colposcopy increases the sensitivity of the colposcopic examination in women referred with abnormal cytology. In this study we have reanalyzed the performance of DSI and conventional colposcopy for new referral conditions and for low-grade cytology referrals versus high-grade cytology referrals. METHOD. Data from a previous validation trial was used to assess the performance of DSI in different cytology groups:Women referred with BMD (borderline and mild dyskaryosis) cytology and women referred with NBMD cytology either hrHPV positive or negative were separately analyzed. Furthermore, we tried to assess the clinical performance by appropriate filtering of patients to replicate two different referral strategies. RESULTS. The sensitivity of DSI and conventional colposcopy to detect CIN2+ lesions in women referred with BMD cytology is 82% and 44% respectively (p= 0.001) and in the NBMD group 77% and 64% respectively (p= 0.24). If the two techniques are combined the sensitivity is 85%.When the conditions of new screening strategies are applied DSI colposcopy has a higher sensitivity to detect CIN2+ than conventional colposcopy. Findings are similar when CIN3+ is used as a threshold. CONCLUSION. We found that in most cases DSI colposcopy has a higher sensitivity than conventional colposcopy, even when referral criteria are changed. Unlike conventional colposcopy, the sensitivity of colposcopy with DSI in low-grade cytology referrals was found similar to the sensitivity in high-grade cytology referrals. This suggests that a baseline colposcopy sensitivity may be possible with the adjunctive use of the DSI map, irrespective of referral cytology.
Assuntos
Colo do Útero/patologia , Colposcopia/métodos , Detecção Precoce de Câncer/métodos , Imagem Óptica/métodos , Ácido Acético , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Estudos Prospectivos , Encaminhamento e Consulta , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
Several countries are in the process of switching to high-risk human papillomavirus (hrHPV) 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 fulfil 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-enzyme immunoassay. These latter two hrHPV DNA assays were validated in large randomized trials and cohorts with a follow-up duration of 8 years or more. Eligible studies citing the 2009 guideline were retrieved from Scopus (http://www.scopus.com) 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 Abbott RealTime High Risk HPV test were consistently validated in two and three studies, respectively, whereas the 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 the following: Cervista HPV HR Test, GP5+/6+ PCR-LMNX, an in-house E6/E7 RT quantitative PCR and MALDI-TOF (matrix-assisted laser desorption-ionization time-of-flight). 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 awaited to inform us about its utility in cervical cancer screening at 5-year or longer intervals.
Assuntos
Detecção Precoce de Câncer/métodos , Técnicas de Genotipagem/métodos , Técnicas de Diagnóstico Molecular/métodos , Papillomaviridae/isolamento & purificação , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Feminino , Humanos , Papillomaviridae/classificação , Papillomaviridae/genética , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: The focus of testing the dynamic spectral imaging (DSI) colposcope has been on the technical characteristics and clinical performance. However, aspects from a patient's perspective are just as important. METHODS: This study was designed as a substudy of the DSI validation study, a prospective comparative, multicenter clinical trial to assess the clinical performance of DSI colposcopy. All women included in this study were asked to complete two questionnaires: a patient characteristics questionnaire and a patient satisfaction questionnaire. RESULTS: In the initial study a total of 239 women were included in the intention-to-treat cohort. Of these, 230 women (96.2%) completed both questionnaires. When assessing the women's preferences for some of the possible uses of DSI colposcopy, a high level of agreement was noted for all potential implementations. In general, women found the additional time DSI colposcopy took acceptable: just 15 women (6.5%) thought the time DSI colposcopy took made them feel uncomfortable. Furthermore, women ranked test accuracy as the most important characteristic, followed by (more) rapid testing and comfort. Quick notification of the results and costs were considered the least important characteristics. CONCLUSION: Women are willing to accept discomfort in the form of an additional or longer test if there is clinical benefit.
Assuntos
Colposcopia/normas , Interpretação de Imagem Assistida por Computador/normas , Preferência do Paciente , Adulto , Colposcopia/economia , Feminino , HumanosRESUMO
BACKGROUND: The association between childhood trauma and psychotic and depressive symptomatology is well established. However, less is known about the specificity and course of these symptoms in relation to childhood trauma. METHOD: In a large sample (n = 2765) of patients with psychosis (n = 1119), their siblings (n = 1057) and controls (n = 589), multivariate (mixed-effects) regression analyses with multiple outcomes were performed to examine the association between childhood trauma and psychotic and depressive symptomatology over a 3-year period. RESULTS: A dose-response relationship was found between childhood trauma and psychosis. Abuse was more strongly associated with positive symptoms than with negative symptoms whereas the strength of the associations between neglect and positive and negative symptoms was comparable. In patients, similar associations between childhood trauma and psychotic or depressive symptoms were found, and in siblings and controls, stronger associations were found between trauma and depressive symptomatology. Childhood trauma was not related to a differential course of symptoms over a 3-year time period. CONCLUSIONS: In congruence with earlier work, our findings suggest that childhood trauma, and abuse in particular, is associated with (subthreshold) psychosis. However, childhood trauma does not seem to be associated with a differential course of symptoms, nor does it uniquely heighten the chance of developing (subthreshold) psychotic symptomatology. Our results indicate that trauma may instead contribute to a shared vulnerability for psychotic and depressive symptoms.
Assuntos
Maus-Tratos Infantis/psicologia , Depressão/psicologia , Progressão da Doença , Transtornos Psicóticos/psicologia , Adulto , Criança , Maus-Tratos Infantis/estatística & dados numéricos , Depressão/epidemiologia , Depressão/etiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Países Baixos , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/etiologia , Fatores de Risco , IrmãosRESUMO
The LMNX genotyping kit HPV GP (LMNX) is based on the clinically validated GP5+/6+ PCR, with a genotyping readout as an alternative for the more established enzyme immunoassay (EIA) detection of 14 targeted high-risk human papillomavirus (HPV) types. LMNX is additionally provided with an internal control probe. Here, we present an analysis of the clinical performance of the LMNX using a sample panel and infrastructure provided by the international VALGENT (Validation of Genotyping Tests) project. This panel consisted of cervical specimens from approximately 1,000 women attending routine screening, "enriched" with 300 women with abnormal cytology. Cases were defined as women classified with cervical intraepithelial neoplasia (CIN) grade 2+ (CIN2+) (n = 102) or CIN3+ (n = 55) within the previous 18 months. Controls were women who had normal cytology results over two subsequent screening rounds at a 3-year interval (n = 746). The GP5+/6+-PCR EIA (EIA) was used as a comparator assay and showed sensitivities of 94.1% and 98.2% for CIN2+ and CIN3+, respectively, with a clinical specificity of 92.4% among women aged ≥ 30 years. The LMNX demonstrated clinical sensitivities of 96.1% for CIN2+ and of 98.2% for CIN3+ and a clinical specificity of 92.6% for women aged ≥ 30 years. The LMNX and EIA were in high agreement (Cohen's kappa = 0.969) for the detection of 14 hrHPVs in aggregate, and no significant difference was observed (McNemar's P = 0.629). The LMNX internal control detected 0.6% inadequate specimens. Based on our study results, we consider the LMNX, similarly to the EIA, useful for HPV-based cervical cancer screening.
Assuntos
Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/normas , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Adulto , Colo do Útero/patologia , Colo do Útero/virologia , Feminino , Humanos , Pessoa de Meia-Idade , Sondas de Oligonucleotídeos , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Padrões de Referência , Sensibilidade e Especificidade , Adulto Jovem , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
BACKGROUND: Shortening the duration of untreated psychosis (DUP) - with the aim of improving the prognosis of psychotic disorders - requires an understanding of the causes of treatment delay. Current findings concerning several candidate risk factors of a longer DUP are inconsistent. Our aim was to identify factors contributing to DUP in a large sample that represents the treated prevalence of non-affective psychotic disorders. METHOD: Patients with a non-affective psychotic disorder were recruited from mental health care institutes from 2004 to 2008. Of the 1120 patients enrolled, 852 could be included in the present analysis. Examined candidate factors were gender, educational level, migration status, premorbid adjustment and age at onset of the psychotic disorder. DUP was divided into five ordinal categories: less than one month, one month to three months, three months to six months, six months to twelve months and twelve months and over. An ordinal logistic regression analysis was used to identify the risk factors of a longer DUP. RESULTS: Median DUP was less than one month (IQR 2). The factors migration status (p=0.028), age at onset of the psychotic disorder (p=0.003) and gender (p=0.034) were significantly associated with DUP in our analysis. CONCLUSION: First generation immigrant patients, patients with an early onset of their psychotic disorder and male patients seem at risk of a longer DUP. These findings can assist in designing specific interventions to shorten treatment delay.
Assuntos
Transtornos Psicóticos/terapia , Adolescente , Adulto , Idade de Início , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Adulto JovemRESUMO
PURPOSE: The association between childhood maltreatment (ChM) and psychotic disorders is well established. However, there is an ongoing debate about which factors account for this relationship. One explanation is that the relationship between ChM and psychosis is mediated by adult attachment style. Therefore, in this study, we aimed to investigate whether adult attachment style mediates the relationship between ChM and positive and negative symptomatology. METHODS: We investigated the relation between ChM and psychotic symptoms, taking into account levels of (insecure) attachment, in 131 patients with psychotic illness, 123 siblings and 72 controls. ChM was assessed with the Childhood Trauma Questionnaire (CTQ). Attachment dimensions of anxiety and avoidance were measured using the Psychosis Attachment Measure (PAM). RESULTS: In both patients and siblings, ChM predicted positive symptoms and this relationship was partly mediated by attachment style. This relationship was found to be stronger for siblings than for patients. ChM predicted negative symptoms in patients and siblings. In the patient sample, attachment style did not mediate the relationship between ChM and negative symptoms, whereas attachment style was found to be a mediator in the sibling sample. CONCLUSIONS: ChM was associated with positive and negative symptomatology in both patients and siblings. Particularly in siblings, the relationship between ChM and psychosis seems to be mediated by adult attachment style. Perhaps attachment style may play a more prominent role on a subclinical level.
Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Ansiedade/diagnóstico , Apego ao Objeto , Transtornos Psicóticos/diagnóstico , Irmãos/psicologia , Adulto , Ansiedade/genética , Ansiedade/psicologia , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/genética , Transtornos Psicóticos/psicologia , Inquéritos e Questionários , Adulto JovemRESUMO
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.
Assuntos
Antígeno Ki-67/análise , Proteínas de Neoplasias/análise , Infecções por Papillomavirus/diagnóstico , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Colposcopia/métodos , Estudos Transversais , Inibidor p16 de Quinase Dependente de Ciclina , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Incidência , Estudos Longitudinais , Pessoa de Meia-Idade , Teste de Papanicolaou/métodos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Estudos Retrospectivos , Fatores de Risco , Coloração e Rotulagem/métodos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/métodos , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
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.
Assuntos
Biomarcadores/metabolismo , Metilação de DNA , Infecções por Papillomavirus/diagnóstico , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Molécula 1 de Adesão Celular , Moléculas de Adesão Celular/metabolismo , Colposcopia , Detecção Precoce de Câncer , Feminino , Seguimentos , Testes Genéticos/métodos , Genótipo , Humanos , Imunoglobulinas/metabolismo , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Proteínas Proteolipídicas Associadas a Linfócitos e Mielina/metabolismo , Valor Preditivo dos Testes , Curva ROC , Sensibilidade e Especificidade , Manejo de Espécimes , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Displasia do Colo do Útero/virologiaRESUMO
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.