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1.
Nature ; 601(7891): 53-57, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34987217

RESUMO

The standard model of particle physics is both incredibly successful and glaringly incomplete. Among the questions left open is the striking imbalance of matter and antimatter in the observable universe1, which inspires experiments to compare the fundamental properties of matter/antimatter conjugates with high precision2-5. Our experiments deal with direct investigations of the fundamental properties of protons and antiprotons, performing spectroscopy in advanced cryogenic Penning trap systems6. For instance, we previously compared the proton/antiproton magnetic moments with 1.5 parts per billion fractional precision7,8, which improved upon previous best measurements9 by a factor of greater than 3,000. Here we report on a new comparison of the proton/antiproton charge-to-mass ratios with a fractional uncertainty of 16 parts per trillion. Our result is based on the combination of four independent long-term studies, recorded in a total time span of 1.5 years. We use different measurement methods and experimental set-ups incorporating different systematic effects. The final result, [Formula: see text], is consistent with the fundamental charge-parity-time reversal invariance, and improves the precision of our previous best measurement6 by a factor of 4.3. The measurement tests the standard model at an energy scale of 1.96 × 10-27 gigaelectronvolts (confidence level 0.68), and improves ten coefficients of the standard model extension10. Our cyclotron clock study also constrains hypothetical interactions mediating violations of the clock weak equivalence principle (WEPcc) for antimatter to less than 1.8 × 10-7, and enables the first differential test of the WEPcc using antiprotons11. From this interpretation we constrain the differential WEPcc-violating coefficient to less than 0.030.

2.
Nature ; 596(7873): 514-518, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34433946

RESUMO

Efficient cooling of trapped charged particles is essential to many fundamental physics experiments1,2, to high-precision metrology3,4 and to quantum technology5,6. Until now, sympathetic cooling has required close-range Coulomb interactions7,8, but there has been a sustained desire to bring laser-cooling techniques to particles in macroscopically separated traps5,9,10, extending quantum control techniques to previously inaccessible particles such as highly charged ions, molecular ions and antimatter. Here we demonstrate sympathetic cooling of a single proton using laser-cooled Be+ ions in spatially separated Penning traps. The traps are connected by a superconducting LC circuit that enables energy exchange over a distance of 9 cm. We also demonstrate the cooling of a resonant mode of a macroscopic LC circuit with laser-cooled ions and sympathetic cooling of an individually trapped proton, reaching temperatures far below the environmental temperature. Notably, as this technique uses only image-current interactions, it can be easily applied to an experiment with antiprotons1, facilitating improved precision in matter-antimatter comparisons11 and dark matter searches12,13.

3.
Nature ; 575(7782): 310-314, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31723290

RESUMO

Astrophysical observations indicate that there is roughly five times more dark matter in the Universe than ordinary baryonic matter1, and an even larger amount of the Universe's energy content is attributed to dark energy2. However, the microscopic properties of these dark components remain unknown. Moreover, even ordinary matter-which accounts for five per cent of the energy density of the Universe-has yet to be understood, given that the standard model of particle physics lacks any consistent explanation for the predominance of matter over antimatter3. Here we present a direct search for interactions of antimatter with dark matter and place direct constraints on the interaction of ultralight axion-like particles (dark-matter candidates) with antiprotons. If antiprotons have a stronger coupling to these particles than protons do, such a matter-antimatter asymmetric coupling could provide a link between dark matter and the baryon asymmetry in the Universe. We analyse spin-flip resonance data in the frequency domain acquired with a single antiproton in a Penning trap4 to search for spin-precession effects from ultralight axions, which have a characteristic frequency governed by the mass of the underlying particle. Our analysis constrains the axion-antiproton interaction parameter to values greater than 0.1 to 0.6 gigaelectronvolts in the mass range from 2 × 10-23 to 4 × 10-17 electronvolts, improving the sensitivity by up to five orders of magnitude compared with astrophysical antiproton bounds. In addition, we derive limits on six combinations of previously unconstrained Lorentz- and CPT-violating terms of the non-minimal standard model extension5.

4.
Phys Rev Lett ; 131(9): 093201, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37721828

RESUMO

Light-ion trap (LIONTRAP), a high-precision Penning-trap mass spectrometer, was used to determine the atomic mass of ^{4}He. Here, we report a 12 parts-per-trillion measurement of the mass of a ^{4}He^{2+} ion, m(^{4}He^{2+})=4.001 506 179 651(48) u. From this, the atomic mass of the neutral atom can be determined without loss of precision: m(^{4}He)=4.002 603 254 653(48) u. This result is slightly more precise than the current CODATA18 literature value but deviates by 6.6 standard deviations.

5.
Nature ; 550(7676): 371-374, 2017 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-29052625

RESUMO

Precise comparisons of the fundamental properties of matter-antimatter conjugates provide sensitive tests of charge-parity-time (CPT) invariance, which is an important symmetry that rests on basic assumptions of the standard model of particle physics. Experiments on mesons, leptons and baryons have compared different properties of matter-antimatter conjugates with fractional uncertainties at the parts-per-billion level or better. One specific quantity, however, has so far only been known to a fractional uncertainty at the parts-per-million level: the magnetic moment of the antiproton, . The extraordinary difficulty in measuring with high precision is caused by its intrinsic smallness; for example, it is 660 times smaller than the magnetic moment of the positron. Here we report a high-precision measurement of in units of the nuclear magneton µN with a fractional precision of 1.5 parts per billion (68% confidence level). We use a two-particle spectroscopy method in an advanced cryogenic multi-Penning trap system. Our result = -2.7928473441(42)µN (where the number in parentheses represents the 68% confidence interval on the last digits of the value) improves the precision of the previous best measurement by a factor of approximately 350. The measured value is consistent with the proton magnetic moment, µp = 2.792847350(9)µN, and is in agreement with CPT invariance. Consequently, this measurement constrains the magnitude of certain CPT-violating effects to below 1.8 × 10-24 gigaelectronvolts, and a possible splitting of the proton-antiproton magnetic moments by CPT-odd dimension-five interactions to below 6 × 10-12 Bohr magnetons.

6.
Phys Rev Lett ; 128(4): 043001, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35148134

RESUMO

A method is proposed to determine the M1 nuclear transition amplitude and hence the lifetime of the "nuclear clock transition" between the low-lying (∼8 eV) first isomeric state and the ground state of ^{229}Th from a measurement of the ground-state g factor of few-electron ^{229}Th ions. As a tool, the effect of nuclear hyperfine mixing in highly charged ^{229}Th ions such as ^{229}Th^{89+} or ^{229}Th^{87+} is used. The ground-state-only g-factor measurement would also provide first experimental evidence of nuclear hyperfine mixing in atomic ions. Combining the measurements for H-, Li-, and B-like ^{229}Th ions has a potential to improve the initial result for a single charge state and to determine the nuclear magnetic moment to a higher accuracy than that of the currently accepted value. The calculations include relativistic, interelectronic-interaction, QED, and nuclear effects.

7.
Nature ; 524(7564): 196-9, 2015 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-26268189

RESUMO

Invariance under the charge, parity, time-reversal (CPT) transformation is one of the fundamental symmetries of the standard model of particle physics. This CPT invariance implies that the fundamental properties of antiparticles and their matter-conjugates are identical, apart from signs. There is a deep link between CPT invariance and Lorentz symmetry--that is, the laws of nature seem to be invariant under the symmetry transformation of spacetime--although it is model dependent. A number of high-precision CPT and Lorentz invariance tests--using a co-magnetometer, a torsion pendulum and a maser, among others--have been performed, but only a few direct high-precision CPT tests that compare the fundamental properties of matter and antimatter are available. Here we report high-precision cyclotron frequency comparisons of a single antiproton and a negatively charged hydrogen ion (H(-)) carried out in a Penning trap system. From 13,000 frequency measurements we compare the charge-to-mass ratio for the antiproton (q/m)p- to that for the proton (q/m)p and obtain (q/m)p-/(q/m)p − 1 =1(69) × 10(-12). The measurements were performed at cyclotron frequencies of 29.6 megahertz, so our result shows that the CPT theorem holds at the atto-electronvolt scale. Our precision of 69 parts per trillion exceeds the energy resolution of previous antiproton-to-proton mass comparisons as well as the respective figure of merit of the standard model extension by a factor of four. In addition, we give a limit on sidereal variations in the measured ratio of <720 parts per trillion. By following the arguments of ref. 11, our result can be interpreted as a stringent test of the weak equivalence principle of general relativity using baryonic antimatter, and it sets a new limit on the gravitational anomaly parameter of |α − 1| < 8.7 × 10(-7).

8.
Br J Dermatol ; 182(4): 1026-1033, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31302935

RESUMO

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/complicações
9.
Nature ; 506(7489): 467-70, 2014 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-24553144

RESUMO

The quest for the value of the electron's atomic mass has been the subject of continuing efforts over the past few decades. Among the seemingly fundamental constants that parameterize the Standard Model of physics and which are thus responsible for its predictive power, the electron mass me is prominent, being responsible for the structure and properties of atoms and molecules. It is closely linked to other fundamental constants, such as the Rydberg constant R∞ and the fine-structure constant α (ref. 6). However, the low mass of the electron considerably complicates its precise determination. Here we combine a very precise measurement of the magnetic moment of a single electron bound to a carbon nucleus with a state-of-the-art calculation in the framework of bound-state quantum electrodynamics. The precision of the resulting value for the atomic mass of the electron surpasses the current literature value of the Committee on Data for Science and Technology (CODATA) by a factor of 13. This result lays the foundation for future fundamental physics experiments and precision tests of the Standard Model.

10.
Nature ; 509(7502): 596-9, 2014 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-24870545

RESUMO

One of the fundamental properties of the proton is its magnetic moment, µp. So far µp has been measured only indirectly, by analysing the spectrum of an atomic hydrogen maser in a magnetic field. Here we report the direct high-precision measurement of the magnetic moment of a single proton using the double Penning-trap technique. We drive proton-spin quantum jumps by a magnetic radio-frequency field in a Penning trap with a homogeneous magnetic field. The induced spin transitions are detected in a second trap with a strong superimposed magnetic inhomogeneity. This enables the measurement of the spin-flip probability as a function of the drive frequency. In each measurement the proton's cyclotron frequency is used to determine the magnetic field of the trap. From the normalized resonance curve, we extract the particle's magnetic moment in terms of the nuclear magneton: µp = 2.792847350(9)µN. This measurement outperforms previous Penning-trap measurements in terms of precision by a factor of about 760. It improves the precision of the forty-year-old indirect measurement, in which significant theoretical bound state corrections were required to obtain µp, by a factor of 3. By application of this method to the antiproton magnetic moment, the fractional precision of the recently reported value can be improved by a factor of at least 1,000. Combined with the present result, this will provide a stringent test of matter/antimatter symmetry with baryons.

11.
Phys Rev Lett ; 123(17): 173001, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31702246

RESUMO

The recently established agreement between experiment and theory for the g factors of lithiumlike silicon and calcium ions manifests the most stringent test of the many-electron bound-state quantum electrodynamics (QED) effects in the presence of a magnetic field. In this Letter, we present a significant simultaneous improvement of both theoretical g_{th}=2.000 889 894 4 (34) and experimental g_{exp}=2.000 889 888 45 (14) values of the g factor of lithiumlike silicon ^{28}Si^{11+}. The theoretical precision now is limited by the many-electron two-loop contributions of the bound-state QED. The experimental value is accurate enough to test these contributions on a few percent level.

12.
Phys Rev Lett ; 122(4): 043201, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30768304

RESUMO

We report on the first detailed study of motional heating in a cryogenic Penning trap using a single antiproton. Employing the continuous Stern-Gerlach effect we observe cyclotron quantum transition rates of 6(1) quanta/h and an electric-field noise spectral density below 7.5(3.4)×10^{-20} V^{2} m^{-2} Hz^{-1}, which corresponds to a scaled noise spectral density below 8.8(4.0)×10^{-12} V^{2} m^{-2}, results which are more than 2 orders of magnitude smaller than those reported by other ion-trap experiments.

13.
Gynecol Oncol ; 149(2): 310-317, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29555332

RESUMO

BACKGROUND: Two etiologic pathways for vulvar squamous cell carcinoma (SCC) are described: in a background of lichen sclerosus and/or differentiated vulvar intraepithelial neoplasia and related to high-risk human papillomavirus (HPV) infection with high grade squamous intraepithelial lesion (HSIL) as precursor. The aim was to compare the predilection site and survival of HPV-related to non HPV-related vulvar SCCs. METHODS: Data of patients treated for primary vulvar SCC at the Radboudumc between March 1988 and January 2015 were analyzed. All histological specimens were tested for HPV with the SPF10/DEIA/LiPA25 system assay and p16INK4a staining was performed using CINtec® histology kit. Vulvar SCCs were considered HPV-related in case of either >25% p16INK4a expression and HPV positivity or >25% p16INK4a expression and HSIL next to the tumor without HPV positivity. Tumor localization, disease specific survival (DSS), disease free survival (DFS) and overall survival (OS) of patients with HPV-related and non HPV-related vulvar SCC were compared. RESULTS: In total 318 patients were included: 55 (17%) had HPV-related (Group 1) and 263 (83%) had non HPV-related vulvar SCC (Group 2). Tumors in Group 1 were significantly more often located at the perineum compared to Group 2, 30% and 14%, respectively (p=0.001). The DSS, DFS and OS were significantly better in HPV-related than in non HPV-related vulvar SCC patients. CONCLUSION: HPV-related vulvar SCCs are more frequently located at the perineum and have a favorable prognosis compared to non HPV-related vulvar SCCs. Both localization and HPV-relation could explain this favorable prognosis. HPV-related vulvar SCC seems to be a separate entity.


Assuntos
Infecções por Papillomavirus/patologia , Líquen Escleroso Vulvar/patologia , Neoplasias Vulvares/patologia , Neoplasias Vulvares/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/patologia , Carcinoma in Situ/virologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Prognóstico
14.
Am J Transplant ; 17(6): 1563-1573, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28009475

RESUMO

Female renal transplant recipients (RTRs) have an increased risk for developing human papillomavirus (HPV)-related (pre)malignant lesions of the genital tract. This study aims to assess the genital prevalence of HPV before and after renal transplantation (RT). In female patients who were counseled for RT at the Radboud University Medical Center Nijmegen, the Netherlands, gynecological examination was performed at first visit, and 1 and 2 years later. HPV self-sampling and questionnaires on sexual behavior were performed every 3 months. In 65 patients who underwent RT, the high-risk human papillomavirus (hrHPV) prevalence as assessed with the highly sensitive SPF10 -LiPA25 test increased significantly from 19% before to 31% after RT (p = 0.045). Based upon the clinically validated Cobas 4800 HPV test, the hrHPV prevalence increased from 10% before to 14% after RT (p = 0.31). During follow-up, no changes in sexual behavior were reported. Thirty-three patients who did not undergo RT showed a hrHPV prevalence of 21% at study entry and of 27% after 12 months with the sensitive test, and a stable prevalence of 16% with the clinically validated test. The results of this study indicate that activation of latent HPV infections may contribute to the increased risk of HPV-related (pre)malignant lesions in female RTRs.


Assuntos
Falência Renal Crônica/virologia , Transplante de Rim/métodos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Ativação Viral , Adulto , Idoso , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/cirurgia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Infecções por Papillomavirus/virologia , Prevalência , Prognóstico , Fatores de Risco , Comportamento Sexual , Transplantados , Adulto Jovem
15.
Phys Rev Lett ; 119(3): 033001, 2017 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-28777624

RESUMO

We report on the precise measurement of the atomic mass of a single proton with a purpose-built Penning-trap system. With a precision of 32 parts per trillion our result not only improves on the current CODATA literature value by a factor of 3, but also disagrees with it at a level of about 3 standard deviations.

16.
BJOG ; 124(9): 1356-1363, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28391609

RESUMO

OBJECTIVE: To compare the sensitivity of high-risk human papillomavirus (hrHPV) and genotype detection in self-collected urine samples in the morning (U1), and later on (U2), brush-based self-samples (SS), and clinician-taken smears (CTS) for detecting cervical intraepithelial neoplasia grade 2+ (CIN2+) in a colposcopic referral population. DESIGN: Cross-sectional single-centre study. SETTING: A colposcopy clinic in Spain. POPULATION: A cohort of 113 women referred for colposcopy after an abnormal Pap smear. METHODS: Women undergoing colposcopy with biopsy for abnormal Pap smears were sent a device (Colli-Pee™, Novosanis, Wijnegem, Belgium) to collect U1 on the morning of colposcopy. U2, CTS, and SS (Evalyn brush™, Rovers Medical Devices B.V., Oss, the Netherlands) were also analysed. All samples were tested for HPV DNA using the analytically sensitive SPF10-DEIA-LiPA25 assay and the clinically validated GP5+/6+-EIA-LMNX. MAIN OUTCOME MEASURES: Histologically confirmed CIN2+ and hrHPV positivity for 14 high-risk HPV types. RESULTS: Samples from 91 patients were analysed. All CIN3 cases (n = 6) tested positive for hrHPV in CTS, SS, U1, and U2 with both HPV assays. Sensitivity for CIN2+ with the SPF10 system was 100, 100, 95, and 100%, respectively. With the GP5+/6+ assay, sensitivity was 95% in all sample types. The sensitivities and specificities for both tests on each of the sample types did not significantly differ. There was 10-14% discordance on hrHPV genotype. CONCLUSIONS: CIN2+ detection using HPV testing of U1 shows a sensitivity similar to that of CTS or brush-based SS, and is convenient. There was substantial to almost excellent agreement between all samples on genotype with both hrHPV assays. There was no advantage in testing U1 compared with U2 samples. TWEETABLE ABSTRACT: Similar CIN2+ sensitivity for HPV testing in first-void urine, physician-taken smear and brush-based self-sample.


Assuntos
DNA Viral/urina , Autoavaliação Diagnóstica , Teste de Papanicolaou , Infecções por Papillomavirus/diagnóstico , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal/métodos , Adolescente , Adulto , Biomarcadores/urina , Colposcopia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/urina , Estudos Prospectivos , Sensibilidade e Especificidade , Triagem , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/urina , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/urina , Displasia do Colo do Útero/virologia
17.
Am J Transplant ; 15(3): 723-33, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25675976

RESUMO

Immunosuppressive treatment of organ transplant recipients is associated with an increase in the occurrence of human papillomavirus (HPV) related anogenital (pre)malignancies. This cohort study investigated the genotype-specific prevalence of HPV infections in a large cohort of female renal transplant recipients (RTRs). Participants self-collected a cervicovaginal sample for detection and genotyping of HPV. Besides, they completed a questionnaire regarding sociodemographic variables, medical data and sexual behavior. Anogenital screening was offered to all HPV-positive participants. A total number of 218 female RTRs was included. The prevalence of mucosal HPV infections was 27.1% and 17.4% for high risk HPV in particular. The studied cohort showed a broad range of HPV genotypes and multiple HPV genotypes were found in 27.1% of HPV-positive patients. Seven participants were identified with occult premalignant anogenital lesions. In conclusion, this study shows a high point-prevalence of HPV in female RTRs (age-matched West-European general population: 9-10%) with a shift in the distribution of genotypes as compared with the general population. Moreover, a substantial number of patients with occult premalignancies was identified. The introduction of self-sampling for HPV positivity can help in early detection of (pre)malignant anogenital lesions in this vulnerable population.


Assuntos
Colo do Útero/virologia , Transplante de Rim , Infecções por Papillomavirus/complicações , Vagina/virologia , Estudos de Coortes , Feminino , Humanos
18.
J Clin Microbiol ; 53(10): 3272-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26246482

RESUMO

As the demand for human papillomavirus (HPV)-related cervical screening increases, emerging HPV tests must be evaluated robustly using well-annotated samples, such as those generated in the Validation of HPV Genotyping Tests (VALGENT) framework. Through VALGENT, we assessed the performance of the BD Onclarity HPV assay, which detects 14 high-risk (HR) types and resolves six individual types and three groups of types. Consecutive samples from a screening population (n = 1,000), enriched with cytologically abnormal samples (n = 300), that had been tested previously with the GP5+/6+ PCR enzyme immunoassay (EIA) and the GP5+/6+ PCR LMNX assay (Diassay) were tested with the Onclarity assay. Type-specific HPV prevalences were analyzed according to age and cytological result. The accuracy of the Onclarity assay for the detection of cervical intraepithelial neoplasia grade 2+ (CIN2+) and CIN3+ was assessed relative to the GP5+/6+ EIA results by using noninferiority criteria. Overall agreement and type-specific agreement between the Onclarity assay and the GP5+/6+ LMNX assay were assessed. The prevalence of HPV types 16, 18, 31, and 45 increased with the severity of cytological results (P for trend, <0.05). For the detection of CIN2+, the Onclarity assay had a relative sensitivity of 1.02 (95% confidence interval [CI], 0.99 to 1.05; P < 0.001 for noninferiority) and a relative specificity of 0.99 (95% CI, 0.97 to 1.00; P = 0.186 for noninferiority). The kappa for agreement between the Onclarity assay and the GP5+/6+ LMNX assay for HR-HPV was 0.92 (95% CI, 0.89 to 0.94), and values for the six individual types ranged from 0.78 (95% CI, 0.68 to 0.87) for HPV-52 to 0.96 (95% CI, 0.93 to 0.99) for HPV-16. These data suggest that the Onclarity assay offers applications for clinical workstreams while providing genotyping information that may be useful for risk stratification beyond types 16 and 18.


Assuntos
Detecção Precoce de Câncer/métodos , Técnicas de Genotipagem/métodos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Displasia do Colo do Útero/diagnóstico , Adolescente , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Sensibilidade e Especificidade , Adulto Jovem , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia
19.
Br J Dermatol ; 172(1): 196-201, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24976535

RESUMO

BACKGROUND: One-third of Dutch primary school children have cutaneous warts; each year around 20% of them seek medical treatment. However, little is known about the epidemiology of the types of human papillomavirus (HPV) causing these warts. OBJECTIVES: To investigate the distribution of cutaneous wart-associated HPV types in three primary school classes by analysing skin swabs taken from warts, and the forehead, hand dorsum and sole of the foot of included children. METHODS: Using the hyperkeratotic skin lesion polymerase chain reaction/multiplex genotyping assay, each swab sample was used to genotype for 23 cutaneous wart-associated HPV types. RESULTS: Thirty-one (44%) of the 71 children had a total of 69 warts, with a maximum of six warts per child. In the wart swabs, HPV2, HPV27 and HPV57, members of Alphapapillomavirus species 4, were most frequently detected (27%, 32% and 14%, respectively), whereas HPV1 was only found in two plantar warts. The prevalence of HPV carriage, detected in swabs of clinically normal skin of the forehead, left hand and left sole was 80%, with the most prevalent types being HPV1 (59%), HPV2 (42%), HPV63 (25%) and HPV27 (21%). CONCLUSIONS: Cutaneous wart-associated HPV types were highly prevalent in primary school children, but did not correlate with the HPV types in warts. In contrast to the existing literature, HPV1 was frequently detected on clinically normal skin but was much less frequent in warts.


Assuntos
Dermatoses Faciais/epidemiologia , Dermatoses do Pé/epidemiologia , Dermatoses da Mão/epidemiologia , Papillomaviridae/isolamento & purificação , Pele/virologia , Verrugas/epidemiologia , Criança , Dermatoses Faciais/virologia , Feminino , Dermatoses do Pé/virologia , Genótipo , Dermatoses da Mão/virologia , Humanos , Masculino , Países Baixos/epidemiologia , Papillomaviridae/genética , Prevalência , Verrugas/genética , Verrugas/virologia
20.
J Clin Microbiol ; 52(11): 3996-4002, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25210073

RESUMO

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/virologia
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