RESUMEN
High-risk human papillomavirus (hrHPV) DNA tests have excellent sensitivity for detection of cervical intraepithelial neoplasia 2 or higher (CIN2+). A drawback of hrHPV screening, however, is modest specificity. Therefore, hrHPV-positive women might need triage to reduce adverse events and costs associated with unnecessary colposcopy. We compared the performance of HPV16/18 genotyping with a predefined DNA methylation triage test (S5) based on target regions of the human gene EPB41L3, and viral late gene regions of HPV16, HPV18, HPV31 and HPV33. Assays were run using exfoliated cervical specimens from 710 women attending routine screening, of whom 38 were diagnosed with CIN2+ within a year after triage to colposcopy based on cytology and 341 were hrHPV positive. Sensitivity and specificity of the investigated triage methods were compared by McNemar's test. At the predefined cutoff, S5 showed better sensitivity than HPV16/18 genotyping (74% vs 54%, P = 0.04) in identifying CIN2+ in hrHPV-positive women, and similar specificity (65% vs 71%, P = 0.07). When the S5 cutoff was altered to allow equal sensitivity to that of genotyping, a significantly higher specificity of 91% was reached (P < 0.0001). Thus, a DNA methylation test for the triage of hrHPV-positive women on original screening specimens might be a valid approach with better performance than genotyping.
Asunto(s)
Metilación de ADN/genética , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/genética , Femenino , Genotipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 16/patogenicidad , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/aislamiento & purificación , Papillomavirus Humano 18/patogenicidad , Papillomavirus Humano 31/genética , Papillomavirus Humano 31/aislamiento & purificación , Papillomavirus Humano 31/patogenicidad , Humanos , Proteínas de Microfilamentos/genética , Estadificación de Neoplasias , Embarazo , Sensibilidad y Especificidad , Displasia del Cuello del Útero/virologíaRESUMEN
INTRODUCTION: Clinical laboratory work among intermittent and daily waterpipe tobacco smokers has revealed significant risks for tobacco dependence and disease associated with waterpipe tobacco smoking (WTS). No studies have compared these groups directly. This study examined whether WTS frequency was associated with differential puff topography, toxicant exposure, and subjective response using a placebo-control design. METHODS: Eighty participants reporting WTS of 2-5 episodes (LOW; n = 63) or ≥20 episodes (HIGH; n = 17) per month for ≥6 months completed 2 double-blind, counterbalanced 2-hr sessions that were preceded by ≥12hr of tobacco abstinence. Sessions differed by product smoked ad libitum for 45+ min: preferred brand/flavor of waterpipe tobacco (active) or a flavor-matched tobacco-free waterpipe product (placebo). Outcomes included puff topography, plasma nicotine, carboxyhemoglobin (COHb), and subjective response. RESULTS: HIGH users had more puffs, shorter inter-puff-intervals, and a higher total puff volume for placebo relative to active, as well as relative to LOW users during placebo. Plasma nicotine concentrations increased when smoking active (but not placebo) with no significant differences between groups at 25min post-product administration. COHb increased significantly during all conditions; the largest increase was for HIGH users when smoking placebo. There was some evidence of higher baseline scores for nicotine/tobacco nicotine abstinence symptomology. CONCLUSIONS: Higher frequency waterpipe users may be more sensitive to the effects of waterpipe smoke nicotine content. Among HIGH users, higher baseline nicotine/tobacco abstinence symptoms may indicate greater nicotine dependence. These data support continued surveillance of WTS and development of dependence measures specific to this product.
Asunto(s)
Carboxihemoglobina/metabolismo , Nicotina/sangre , Fumar/sangre , Productos de Tabaco/estadística & datos numéricos , Tabaquismo/sangre , Adolescente , Presión Arterial , Monóxido de Carbono/análisis , Método Doble Ciego , Femenino , Aromatizantes , Sustancias Peligrosas , Frecuencia Cardíaca , Humanos , Exposición por Inhalación/análisis , Masculino , Nicotina/administración & dosificación , Fumar/epidemiología , Fumar/fisiopatología , Tabaquismo/epidemiología , Tabaquismo/fisiopatología , Adulto JovenRESUMEN
Testing for high-risk (hr) types of human papillomavirus (HPV) is highly sensitive as a screening test of high-grade cervical intraepithelial neoplastic (CIN2/3) disease, the precursor of cervical cancer. However, it has a relatively low specificity. Our objective was to develop a prediction rule with a higher specificity, using combinations of human and HPV DNA methylation. Exfoliated cervical specimens from colposcopy-referral cohorts in London were analyzed for DNA methylation levels by pyrosequencing in the L1 and L2 regions of HPV16, HPV18, HPV31 and human genes EPB41L3, DPYS and MAL. Samples from 1,493 hrHPV-positive women were assessed and of these 556 were found to have CIN2/3 at biopsy; 556 tested positive for HPV16 (323 CIN2/3), 201 for HPV18 (73 CIN2/3) and 202 for HPV31 (98 CIN2/3). The prediction rule included EPB41L3 and HPV and had area under curve 0.80 (95% CI 0.78-0.82). For 90% sensitivity, specificity was 36% (33-40) and positive predictive value (PPV) was 46% (43-48). By HPV type, 90% sensitivity corresponded to the following specificities and PPV, respectively: HPV16, 38% (32-45) and 67% (63-71); HPV18, 53% (45-62) and 52% (45-59); HPV31, 39% (31-49) and 58% (51-65); HPV16, 18 or 31, 44% (40-49) and 62% (59-65) and other hrHPV 17% (14-21) and 21% (18-24). We conclude that a methylation assay in hrHPV-positive women might improve PPV with minimal sensitivity loss.
Asunto(s)
Metilación de ADN , Papillomaviridae/genética , Displasia del Cuello del Útero/genética , Displasia del Cuello del Útero/virología , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/virología , Estudios de Cohortes , Islas de CpG , ADN de Neoplasias/genética , ADN Viral/genética , Femenino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Neoplasias del Cuello Uterino/clasificación , Displasia del Cuello del Útero/clasificaciónRESUMEN
High-risk human papillomavirus (HPV) DNA/RNA testing provides higher sensitivity but lower specificity than cytology for the identification of high-grade cervical intraepithelial neoplasia (CIN). Several new HPV tests are now available for this purpose, and a direct comparison of their properties is needed. Seven tests were evaluated with samples in liquid PreservCyt transport medium from 1,099 women referred for colposcopy: the Hybrid Capture 2 (Qiagen), Cobas (Roche), PreTect HPV-Proofer (NorChip), Aptima HPV (Gen-Probe), and Abbott RealTime assays, the BD HPV test, and CINtec p16(INK4a) cytology (mtm laboratories) immunocytochemistry. Sensitivity, specificity, and positive predictive value (PPV) were based on the worst histology found on either the biopsy or the treatment specimen after central review. Three hundred fifty-nine women (32.7%) had CIN grade 2+ (CIN2+), with 224 (20.4%) having CIN3+. For detection of CIN2+, Hybrid Capture 2 had 96.3% sensitivity, 19.5% specificity, and 37.4% PPV. Cobas had 95.2% sensitivity, 24.0% specificity, and 37.6% PPV. The BD HPV test had 95.0% sensitivity, 24.2% specificity, and 37.8% PPV. Abbott RealTime had 93.3% sensitivity, 27.3% specificity, and 38.2% PPV. Aptima had 95.3% sensitivity, 28.8% specificity, and 39.3% PPV. PreTect HPV-Proofer had 74.1% sensitivity, 70.8% specificity, and 55.4% PPV. CINtec p16(INK4a) cytology had 85.7% sensitivity, 54.7% specificity, and 49.1% PPV. Cytology of a specimen taken at colposcopy (mild dyskaryosis or worse) had 88.9% sensitivity, 58.1% specificity, and 50.7% PPV. Our study confirms that, in a referral setting, HPV testing by a number of different tests provides high sensitivity for high-grade disease. Further work is needed to confirm these findings in a routine screening setting.
Asunto(s)
Inmunohistoquímica/métodos , Técnicas de Diagnóstico Molecular/métodos , Papillomaviridae/aislamiento & purificación , Infecciones por Parvoviridae/diagnóstico , Juego de Reactivos para Diagnóstico , Displasia del Cuello del Útero/diagnóstico , Adulto , Femenino , Humanos , Infecciones por Parvoviridae/complicaciones , Sensibilidad y Especificidad , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/virologíaRESUMEN
Patient-provider communication can lead to unhelpful ideas and beliefs about a patient's condition, negatively impacting their clinical outcome. A 34-year-old male Veteran presented for an evaluation of high impact chronic low back pain. Previous interactions with various healthcare providers resulted in the Veteran viewing his condition as ominous and in need of intervention, however clinical findings did not support these beliefs. Our Veteran underwent six visits in the chiropractic clinic with treatment consisting of pain education, utilization of cognitive behavioral principles, active home care exercises and spinal manipulation, resulting in improvements in functional and objective outcome measures. This case report highlights the impact of misalignment between an early contact healthcare provider and patient misunderstanding of their condition on long term outcomes. It serves as an example of how physicians utilizing pathoanatomic explanations to describe a patient's chronic low back pain diagnosis can alter the patient's beliefs about their condition.
La communication entre le fournisseur de soins de santé et le patient peut conduire à des idées et à des croyances inutiles sur l'état du patient, ce qui a un impact négatif sur son résultat clinique. Un vétéran de 34 ans s'est présenté pour une évaluation d'une lombalgie chronique à fort impact. Des interactions antérieures avec divers fournisseurs de soins de santé ont amené le vétéran à considérer son état comme inquiétant et nécessitant une intervention, mais les résultats cliniques n'ont pas appuyé ces croyances. Notre ancien combattant a effectué six visites à la clinique chiropratique subissant chaque fois un traitement consistant en une éducation à la douleur, l'utilisation de principes cognitivo-comportementaux, des exercices de soins actifs à domicile et des manipulations vertébrales, ce qui a entraîné des améliorations dans les mesures de résultats fonctionnels et objectifs. Ce rapport de cas met en évidence l'impact d'un mauvais alignement entre un fournisseur de soins de santé de premier contact et l'incompréhension du patient de son état sur les résultats à long terme. Il sert d'exemple de la façon dont les médecins utilisant des explications d'anatomie pathologique pour décrire le diagnostic de lombalgie chronique d'un patient peuvent modifier l'idée que se fait le patient de son état.
RESUMEN
BACKGROUND: Human papillomavirus (HPV)-based screening is rapidly replacing cytology as the cervical screening modality of choice. In addition to being more sensitive than cytology, it can be done on self-collected vaginal or urine samples. This study will compare the high-risk HPV positivity rates and sensitivity of self-collected vaginal samples using four different collection devices and a urine sample. METHODS: A total of 620 women referred for colposcopy were invited to provide an initial stream urine sample collected with the Colli-Pee device and take two vaginal self-samples, using either a dry flocked swab (DF) and a wet dacron swab (WD), or a HerSwab (HS) and Qvintip (QT) device. HPV testing was performed by the BD Onclarity HPV Assay. RESULTS: A total of 600 vaginal sample pairs were suitable for analysis, and 505 were accompanied by a urine sample. Similar positivity rates and sensitivities for CIN2+ and CIN3+ were seen for DF, WD, and urine, but lower values were seen for QT and HS. No clear user preferences were seen between devices, but women found urine easiest to collect, and were more confident they had taken the sample correctly. The lowest confidence in collection was reported for HS. CONCLUSIONS: Urine, a DF swab, and WD swab all performed well and were well received by the women, whereas the Qvintip and HerSwab devices were less satisfactory. IMPACT: This is the first study to compare five self-sampling methods in the same women taken at the same time. It supports wider use of urine or vaginal self-sampling for cervical screening.
Asunto(s)
Infecciones por Papillomavirus/virología , Autocuidado , Orina/virología , Displasia del Cuello del Útero/virología , Neoplasias del Cuello Uterino/virología , Vagina/virología , Adulto , Detección Precoz del Cáncer/métodos , Femenino , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/orina , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Manejo de Especímenes/métodos , Frotis VaginalRESUMEN
HPV DNA testing is known to be much more sensitive than cytology, but less specific. A range of HPV and related tests in 858 women referred for colposcopy because of an abnormal smear were evaluated to compare the performances of these tests. This article compared the Abbott test to other tests which had been previously evaluated. This test was a real true test for 14 high-risk HPV types. The Abbott test was found to be highly sensitive for cervical intraepithelial neoplasia grade 3 or worse (CIN3+) (98.9%) with a specificity of 31.5%. These numbers were comparable with the Qiagen HC2 test, the Roche Linear Array and Amplicor tests, and the Gen-Probe APTIMA test. Differences between these tests appeared to be related mostly to the choice of cutoff level. An added feature of the Abbott test was the provision of type specific results for HPV 16 and 18.
Asunto(s)
ADN Viral/aislamiento & purificación , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Reacción en Cadena de la Polimerasa/métodos , Neoplasias del Cuello Uterino/diagnóstico , Cuello del Útero/patología , Cuello del Útero/virología , ADN Viral/genética , Diagnóstico Diferencial , Femenino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Infecciones por Papillomavirus/complicaciones , Sensibilidad y Especificidad , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Frotis VaginalRESUMEN
Several studies have shown that HPV testing is substantially more sensitive than cytology for primary cervical screening. However, less data exist concerning the duration of protection afforded by a negative HPV test compared to a normal cytological outcome. Here we report the long-term findings from the Hammersmith study in women aged 35 or more. HPV testing by Hybrid Capture II was performed on all available samples from the baseline screening visit. Passive surveillance of subsequent cytology screening results for the 2,982 women in the study was undertaken using a national registry. Histological outcomes were sought for all women with abnormal smears. The primary outcome was duration of protection against histologically confirmed CIN2+ afforded by a negative HPV test compared to normal cytology. 2,516 women had at least one further smear at least 1 year after entry and 20 new cases of CIN2+ were identified during a median follow-up of 6.4 years. Including disease identified at baseline, the risk of developing CIN2+ at 1, 5 and 9 years after a normal cytology was 0.33%, 0.83% and 2.20% respectively whereas it was 0.19%, 0.42% and 1.88% after a negative HPV test. HPV testing offered excellent protection from CIN2+ for at least 6 years after a negative test, whereas the protection from cytology began to wane after about 3 years. Substantially more CIN2+ lesions were found in the follow-up period in those initially HPV positive compared to those HPV negative (HR = 6.52, p = 0.001), whereas there was little difference according to initial cytology (HR = 1.64, p = 0.51).
Asunto(s)
ADN Viral/genética , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Frotis Vaginal/métodos , Adenocarcinoma/diagnóstico , Adenocarcinoma/virología , Adulto , Estudios de Cohortes , Colposcopía , Técnicas Citológicas , ADN Viral/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Tamizaje Masivo , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Factores de Tiempo , Reino Unido/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/virologíaRESUMEN
BACKGROUND: The detection of high-risk human papillomavirus (HPV) DNA provides higher sensitivity but lower specificity than cytology for the identification of high-grade cervical intraepithelial neoplasia (CIN). This study compared the sensitivity and specificity of several adjunctive tests for the detection of high-grade CIN in a population referred to colposcopy because of abnormal cytology. METHODS: 953 women participated in the study. Up to seven tests were carried out on a liquid PreservCyt sample: Hybrid Capture II (Digene), Amplicor (Roche), PreTect HPV-Proofer (NorChip), APTIMA HPV assay (Gen-Probe), Linear Array (Roche), Clinical-Arrays (Genomica), and CINtec p16INK4a Cytology (mtm Laboratories) immunocytochemistry. Sensitivity, specificity, and positive predictive value (PPV) were based on the worst histology seen on either the biopsy or the treatment specimen after central review. RESULTS: 273 (28.6%) women had high-grade disease (CIN2+) on worst histology, with 193 (20.2%) having CIN3+. For the detection of CIN2+, Hybrid Capture II had a sensitivity of 99.6%, specificity of 28.4%, and PPV of 36.1%. Amplicor had a sensitivity of 98.9%, specificity of 21.7%, and PPV of 33.5%. PreTect HPV-Proofer had a sensitivity of 73.6%, specificity of 73.1%, and PPV of 52.0%. APTIMA had a sensitivity of 95.2%, specificity of 42.2%, and PPV of 39.9%. CINtec p16INK4a Cytology had a sensitivity of 83.0%, specificity of 68.7%, and PPV of 52.3%. Linear Array had a sensitivity of 98.2%, specificity of 32.8%, and PPV of 37.7%. Clinical-Arrays had a sensitivity of 80.9%, specificity of 37.1%, and PPV of 33.0%.
Asunto(s)
ADN Viral/análisis , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/virología , Adulto , Colposcopía , Femenino , Genotipo , Humanos , Inmunohistoquímica/métodos , Hibridación de Ácido Nucleico/métodos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Papillomaviridae/clasificación , Valor Predictivo de las Pruebas , Curva ROC , Sensibilidad y Especificidad , Frotis VaginalRESUMEN
OBJECTIVE: To ascertain perspectives of multiple stakeholders on contributors to inappropriate care for older adults with multiple chronic conditions. METHOD: Perspectives of 36 purposively sampled patients, clinicians, health systems, and payers were elicited. Data analysis followed a constant comparative method. RESULTS: Structural factors triggering burden and fragmentation include disease-based quality metrics and need to interact with multiple clinicians. The key cultural barrier identified is the assumption that "physicians know best." Inappropriate decision making may result from inattention to trade-offs and adherence to multiple disease guidelines. Stakeholders recommended changes in culture, structure, and decision making. Care options and quality metrics should reflect a focus on patients' priorities. Clinician-patient partnerships should reflect patients knowing their health goals and clinicians knowing how to achieve them. Access to specialty expertise should not require visits. DISCUSSION: Stakeholders' recommendations suggest health care redesigns that incorporate patients' health priorities into care decisions and realign relationships across patients and clinicians.
Asunto(s)
Servicios de Salud para Ancianos , Afecciones Crónicas Múltiples , Mejoramiento de la Calidad/organización & administración , Anciano , Toma de Decisiones , Femenino , Necesidades y Demandas de Servicios de Salud/organización & administración , Servicios de Salud para Ancianos/organización & administración , Servicios de Salud para Ancianos/normas , Humanos , Masculino , Afecciones Crónicas Múltiples/epidemiología , Afecciones Crónicas Múltiples/terapia , Participación del PacienteRESUMEN
OBJECTIVES: To compare the performance and acceptability of unsupervised self-sampling with clinician sampling for high-risk human papillomavirus (HPV) types for the first time in a UK screening setting. SETTING: Nine hundred and twenty women, from two demographically different centres, attending for routine cervical smear testing. METHODS: Women performed an unsupervised HPV self-test. Immediately afterwards, a doctor or nurse took an HPV test and cervical smear. Women with an abnormality on any test were offered colposcopy. RESULTS: Twenty-one high-grade and 39 low-grade cervical intraepithelial neoplasias (CINs) were detected. The sensitivity for high-grade disease (CIN2+) for the self HPV test was 81% (95% confidence interval [CI] 60-92), clinician HPV test 100% (95% CI 85-100), cytology 81% (95% CI 60-92). The sensitivity of both HPV tests to detect high- and low-grade cervical neoplasia was much higher than that of cytology (self-test 77% [95%CI 65-86], clinician test 80% [95% CI 68-88], cytology 48% [95% CI 36-61]). For both high-grade alone, and high and low grades together, the specificity was significantly higher for cytology (greater than 95%) than either HPV test (between 82% and 87%). The self-test proved highly acceptable to women and they reported that the instructions were easy to understand irrespective of educational level. CONCLUSIONS: Our results suggest that it would be reasonable to offer HPV self-testing to women who are reluctant to attend for cervical smears. This approach should now be directly evaluated among women who have been non-attenders in a cervical screening programme.
Asunto(s)
Papillomaviridae/aislamiento & purificación , Autoexamen/métodos , Frotis Vaginal/métodos , Adulto , Distribución por Edad , Anciano , Algoritmos , Femenino , Humanos , Persona de Mediana Edad , Aceptación de la Atención de Salud , Estándares de Referencia , Sensibilidad y Especificidad , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/virologíaRESUMEN
Background: Human papillomavirus (HPV) testing from clinician-collected cervical and self-collected cervico-vaginal samples is more sensitive for detecting CIN2+/CIN3+ than cytology-based screening, stimulating interest in HPV testing from urine. The objective was to determine the performance of the Trovagene HPV test for the detection of CIN2+ from urine and PreservCyt cervical samples.Methods: Women referred for colposcopy at St Mary's Hospital (London, United Kingdom), following abnormal cytology, were recruited to this diagnostic accuracy study by convenience sampling (September 2011 to April 2013). A total of 501 paired urine and cervical samples were collected. Primary outcomes were sensitivity for CIN2+/CIN3+ and specificity for Asunto(s)
Detección Precoz del Cáncer/métodos
, Tamizaje Masivo/métodos
, Papillomaviridae/aislamiento & purificación
, Infecciones por Papillomavirus/orina
, Displasia del Cuello del Útero/orina
, Neoplasias del Cuello Uterino/orina
, Adulto
, Anciano
, Cuello del Útero/patología
, Colposcopía
, ADN Viral/aislamiento & purificación
, Estudios de Factibilidad
, Femenino
, Humanos
, Persona de Mediana Edad
, Infecciones por Papillomavirus/diagnóstico
, Infecciones por Papillomavirus/patología
, Infecciones por Papillomavirus/virología
, Estudios Prospectivos
, ARN Viral/aislamiento & purificación
, Derivación y Consulta
, Sensibilidad y Especificidad
, Manejo de Especímenes
, Reino Unido
, Urinálisis/métodos
, Neoplasias del Cuello Uterino/diagnóstico
, Neoplasias del Cuello Uterino/patología
, Neoplasias del Cuello Uterino/virología
, Frotis Vaginal
, Displasia del Cuello del Útero/diagnóstico
, Displasia del Cuello del Útero/patología
, Displasia del Cuello del Útero/virología
RESUMEN
BACKGROUND: Two transport media, PreservCyt and SurePath, are widely used for cervical cytology screening. There are concerns that they may perform differently for HPV testing. OBJECTIVES: A comparison of the performance of six different HPV tests in SurePath and PreservCyt in a referral population using two samples from each woman. The primary goal was to compare the performance of each test in the two media. Comparisons between assays and viral load comparisons between media were secondary aims. STUDY DESIGN: Two cervical samples were collected in random order at the same visit in women with abnormal cytology. One sample was placed in 20ml of PreservCyt and the other in 10ml of SurePath. Aliquots were taken for 4 DNA based tests: digene HC2 High-Risk HPV DNA Test, Abbott Realtime, BD Onclarity and Genera PapType, an RNA based test-: Hologic Aptima and a protein test: OncoHealth. RESULTS: 630 sample pairs were included in the analyses. For all tests except the protein test sensitivities were in excess of 90% for CIN2+ and 95% for CIN3+ for both media and with no significant differences except for a lower sensitivity for CIN2+ of Aptima in SurePath (93% vs 98%, P=0.005). Specificity for Asunto(s)
Detección Precoz del Cáncer/métodos
, Papillomaviridae/clasificación
, Papillomaviridae/aislamiento & purificación
, Infecciones por Papillomavirus/diagnóstico
, Manejo de Especímenes/métodos
, Adulto
, Pruebas Diagnósticas de Rutina/métodos
, Femenino
, Humanos
, Papillomaviridae/genética
, Estudios Prospectivos
, Sensibilidad y Especificidad
, Carga Viral/métodos
RESUMEN
BACKGROUND: Persistent infection %by with high risk human papillomavirus (hrHPV) types causes cervical cancer but most women who test positive are at very low risk of neoplasia. Strategies are needed which can retain high sensitivity of hrHPV testing but reduce the number of false-positives. We showed previously that a combination DNA methylation triage assay for HPV types 16, 18 and 31 and human gene EPB41L3 was useful to identify high grade cervical lesions. OBJECTIVE: Assess whether measurement of DNA methylation in HPV type 33 can improve the previous classifier. METHODS: A London colposcopy referral group of 1493 women of whom 556 (37%) had histologically-confirmed CIN (cervical intraepithelial neoplasia) 2 or 3 that included 114 HPV33 positive women with methylation measured for three L2 CpGs 5557, 5560 and 5566. Discrimination performance was assessed for the new classifier S5, built by adding HPV33 to the earlier classifier. RESULTS: HPV33 methylation measurement improved prediction among HPV33 positive women. Receiver operating characteristic analyses showed an area under the curve (AUC) for HPV33 methylation of 0.68 (95% CI 0.57-0.78). The earlier risk score was significantly improved by HPV33 methytlation (AUC = 0.82 vs 0.80; P < 0.001). For 90% sensitivity the specificity for CIN2/3 was 49% (95% CI 46-52%). CONCLUSIONS: Measurement of HPV33 DNA methylation contributes independent diagnostic information to EPB41L3 and HPV16, HPV18 and HPV31, and is superior to genotyping. Other HPV and human methylation target regions might be useful to further improve S5.
Asunto(s)
Metilación de ADN/genética , ADN Viral/genética , Genotipo , Neoplasias del Cuello Uterino/genética , Detección Precoz del Cáncer , Femenino , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/patogenicidad , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/patogenicidad , Papillomavirus Humano 31/genética , Papillomavirus Humano 31/patogenicidad , Humanos , Papillomaviridae/genética , Papillomaviridae/patogenicidad , Embarazo , Factores de Riesgo , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virologíaRESUMEN
BACKGROUND: Non-attenders for cervical screening are at increased risk of cervical cancer. Studies offering self-sampling for high-risk Human Papillomavirus (HrHPV) testing have shown greater uptake than sending another invitation for cytology. OBJECTIVES: To explore whether uptake would increase in a less diverse, more stable population than the previous English study, which demonstrated a lower response rate than other studies. The primary objective was whether non-attenders were more likely to respond to a postal invitation, including kit, to collect a self-sample compared with a further invitation for cytology screening. The secondary objective was whether women with an abnormal result would attend for follow-up. METHODS: 6000 non-attenders for screening in this pragmatic, randomized (1:1) controlled trial in Newcastle-upon-Tyne were sent an HPV self-sample kit (intervention) or a further invitation for cytology screening (comparator). RESULTS: 411(13%) responded to the intervention, returning a self-sample (247(8%)) or attending for cytology (164(5%)), compared with 183(6%) attending for cytology, relative risk 2.25 (95% CI 1.90-2.65) (comparator arm). Of those testing hrHPV positive (32(13%)), 19(59%) subsequently attended cytology screening. Of those in the intervention group who attended for cytology screening without returning an hrHPV self-sample (n = 164), 5% (n = 8) were referred for colposcopy - all attended. In the comparator group eight of the nine referred for colposcopy attended. CONCLUSION: Persistent non-responders to invitations for cervical screening are significantly more likely to respond to a postal invitation to return a self-collected sample for HPV testing than a further invitation for cytology screening. However, just over half followed up on this positive HPV result.
Asunto(s)
Tamizaje Masivo/métodos , Cooperación del Paciente , Displasia del Cuello del Útero/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Adulto , Anciano , Alphapapillomavirus/aislamiento & purificación , Inglaterra , Femenino , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/diagnóstico , Manejo de Especímenes , Frotis Vaginal/métodos , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/virologíaRESUMEN
BACKGROUND: HR HPV genotypes when assayed collectively, achieve high sensitivity but low specificity for the prediction of CIN2+. Knowledge of the specific genotypes in an infection may facilitate the use of HR HPV detection in routine clinical practice. OBJECTIVES: To compare the rate of HR HPV detection and the accuracy of CIN2+ prediction between PapType test (Genera Biosystems) and other commercially available HR HPV assays, and to examine the value of full HPV genotyping. STUDY DESIGN: PreservCyt samples from 1099 women referred for abnormal cervical cytology were used. CIN2+ was chosen as the primary end-point but CIN3+ was also evaluated. A hierarchy of HR HPV genotypes was created using PPV and this was used to create 3 groups of genotypes with potentially different management. RESULTS: The PapType assay has a specificity of 22.4% and a sensitivity of 94.6% for CIN2+ prediction. Classification into Groups A (HPV33 and HPV16, very highly predictive), B (HPV31, 18, 52, 35, 58, 51 highly predictive) and C (HPV68, 45, 39, 66, 56, 59, intermediate predictive) could double the specificity (44.5%) but only slightly reduce the sensitivity for CIN2+ (91.5%) and CIN3+ (94.0%). CONCLUSIONS: The PapType assay is a simple, reproducible and effective test for HR HPV detection and genotyping. HPV 33 was found to have a very high PPV and should therefore be managed as for HPV16.
Asunto(s)
Cuello del Útero/virología , Técnicas de Genotipaje/métodos , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/virología , Femenino , Genotipo , Humanos , Prueba de Papanicolaou , Papillomaviridae/genética , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
AIM: To compare triage strategies using different human papillomavirus (HPV) consensus and genotyping tests and a p16(INK4a) test. METHODS: 1228 women referred with a borderline or single mildly dyskaryotic smear. Samples were taken at colposcopy using PreservCyt. Tests included Hybrid Capture 2, Abbott RealTime PCR, BD HPV, Cobas 4800, PreTect HPV-Proofer, APTIMA and p16(INK4a). Results were based on the worst histology within 9 months. RESULTS: 97/1228 (7.9%) women had CIN3+ (203/1228 (17%) CIN2+). HPV testing alone using Hybrid Capture 2, Abbott RealTime PCR, BD HPV, Cobas 4800 or APTIMA had a sensitivity for CIN3+ ranging from 99.0% to 100.0% and specificity for Asunto(s)
Infecciones por Papillomavirus/diagnóstico
, Displasia del Cuello del Útero/diagnóstico
, Neoplasias del Cuello Uterino/diagnóstico
, Adolescente
, Adulto
, Anciano
, ADN Viral/análisis
, Detección Precoz del Cáncer
, Femenino
, Genotipo
, Papillomavirus Humano 16/genética
, Humanos
, Inmunohistoquímica
, Persona de Mediana Edad
, ARN Viral/análisis
, Sensibilidad y Especificidad
, Neoplasias del Cuello Uterino/virología
, Adulto Joven
, Displasia del Cuello del Útero/virología
RESUMEN
BACKGROUND: Waterpipe tobacco smoking usually involves heating flavored tobacco with charcoal and inhaling the resulting smoke after it has passed through water. Waterpipe tobacco smoking increases heart rate and produces subjective effects similar to those reported by cigarette smokers. These responses are thought to be nicotine-mediated, though no placebo-control studies exist. Accordingly, this double-blind, placebo-control study compared the acute physiological and subjective effects of waterpipe tobacco smoking to those produced when participants used a waterpipe to smoke a flavor-matched, tobacco-free preparation. METHODS: Occasional waterpipe tobacco smokers (n = 37; 2-5 monthly smoking episodes for ≥ 6 months) completed two double-blind, counterbalanced sessions that differed by product: preferred brand/flavor of waterpipe tobacco or flavor-matched, tobacco-free preparation. For each 45-min, ad lib smoking episode blood and expired air CO were sampled, cardiovascular and respiratory response were measured, and subjective response was assessed. RESULTS: Waterpipe tobacco smoking significantly increased mean (± SEM) plasma nicotine concentration (3.6 ± 0.7 ng/ml) and heart rate (8.6 ± 1.4 bpm) while placebo did not (0.1 ± 0.0 ng/ml; 1.3 ± 0.9b pm). For carboxyhemoglobin (COHb) and expired air CO, significant increases were observed for tobacco (3.8 ± 0.4%; 27.9 ± 2.6 ppm) and for placebo (3.9 ± 0.4%; 27.7 ± 3.3 ppm) with no differences across condition. Independent of condition, symptoms of nicotine/tobacco abstinence (e.g., "urges to smoke", "anxious") were reduced and direct effects (e.g., "dizzy", "satisfy") increased. DISCUSSION: These results from the first placebo-control study of waterpipe tobacco smoking demonstrate that waterpipe-induced heart rate increases are almost certainly mediated by nicotine though the subjective effects observed in these occasional smokers were not.