Comparison of Onclarity Human Papillomavirus (HPV) Assay with Hybrid Capture II HPV DNA Assay for Detection of Cervical Intraepithelial Neoplasia Grade 2 and 3 Lesions.

Analytical and clinical performance validation is essential before introduction of a new human papillomavirus (HPV) assay into clinical practice. This study compares the new BD Onclarity HPV assay, which detects E6/E7 DNA from 14 high-risk HPV types, to the Hybrid Capture II (HC2) HPV DNA test, to concurrent cytology and histology results, in order to evaluate its performance in detecting high-grade cervical lesions. A population of 567 women, including 325 with ≥ASCUS (where ASCUS stands for atypical cells of undetermined significance) and any HC2 result and 242 with both negative cytology and negative HC2 results, were prospectively enrolled for the study. The overall agreement between Onclarity and HC2 was 94.6% (95% confidence intervals [CI], 92.3% to 96.2%). In this population with a high prevalence of disease, the relative sensitivities (versus adjudicated cervical intraepithelial neoplasia grades 2 and 3 [CIN2+] histology endpoints) of the Onclarity and HC2 tests were 95.2% (95% CI, 90.7% to 97.5%) and 96.9% (95% CI, 92.9% to 98.7%), respectively, and the relative specificities were 50.3% (95% CI, 43.2% to 57.4%) for BD and 40.8% (95% CI, 33.9%, 48.1%) for HC2. These results indicate that the BD Onclarity HPV assay has sensitivity comparable to that of the HC2 assay, with a trend to an increased specificity. Moreover, as Onclarity gives the chance to discriminate between the different genotypes, we calculated the genotype prevalence and the absolute risk of CIN2+: HPV 16 was the most prevalent genotype (19.8%) with an absolute risk of CIN2+ of 77.1%.

HPV self-sampling in CIN2+ detection: sensitivity and specificity of different RLU cut-off of HC2 in specimens from 786 women.

AIMS: Mortality for cervical cancer varies between the different regions of the world, with high rates in low-income countries where screening programmes are not present and organised. However, increasing screening coverage is still a priority in all countries: one way to do that is to base screening on self-sampled screening. The success of a self-sampling screening strategy depends on capacity to recruit unscreened women, on the performance and acceptability of the device and on the clinical performance of the high-risk human papillomavirus (HPV) test. METHODS: This study based on 786 enrolled women investigates the best cut-off value of Hybrid Capture 2 HPV test (HC2) for self-sampled specimens in terms of sensitivity and specificity. RESULTS: In this population, we found that the sensitivity and the specificity for cervical intraepithelial neoplasia grade 2 or more detection of HC2 performed on self-sampled specimens were 82.5% and 82.8%, respectively considering the relative light units (RLU) cut-off value of 1. Increasing the cut-off value the sensitivity decreases and the specificity raises and the best area under the curve for the RLU cut-off value is 1. CONCLUSIONS: Our results confirm that the cut-off value of 1 suggested by Qiagen for PreservCyt specimen is the best cut-off value also for self-sampled specimens.

Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy.

OBJECTIVES: We investigated the role of cardiac troponin I (cTnI) in patients with aggressive malignancies treated with high-dose chemotherapy (HDC). BACKGROUND: High dose chemotherapy is potentially limited by cardiac toxicity. Considering the fact that cardiac dysfunction may become clinically evident weeks or months after HDC, the availability of an early marker of myocardial injury, able to predict late ventricular impairment, is a current need. METHODS: We measured, in 204 patients (45+/-10 years) affected by cancer resistant to conventional treatment, the cTnI plasma concentration after every single cycle of HDC. According to the cTnI value (< or = or >0.4 ng/ml), patients were divided into a troponin positive (cTnI+, n = 65) and a troponin negative (cTnI-, n = 139) group. All patients underwent echocardiographic examination during the following seven months. RESULTS: In the cTnI- group, left ventricular ejection fraction (LVEF) progressively decreased after HDC, reaching a maximal reduction after three months; however, myocardial depression was transient and no longer detectable at later follow-up. By contrast, in the cTnI+ group LVEF reduction was more marked and still evident at the end of the follow-up. In cTnI+ patients, a close relationship between the short-term cTnI increment and the greatest LVEF reduction was found (r = -0.87, p<0.0001). CONCLUSIONS: The elevation of cTnI in patients undergoing HDC for aggressive malignancies accurately predicts the development of future LVEF depression. In this setting, cTnI can be considered a sensitive and reliable marker of acute minor myocardial damage with relevant clinical and prognostic implications.

Determination of 228Ra, 226Ra and 224Ra in natural water via adsorption on MnO2-coated discs.

A fast procedure based on sorption of Ra on MnO2 coated polyamide discs is presented for determination of radium isotopes (i.e. 228Ra, 226Ra, 224Ra) in aqueous samples. The sample discs can be used directly for low-level alpha-spectrometry without the need for further separation and preparation methods to produce planar sample sources. While the activity of alpha-emitting 224Ra and 226Ra can be determined during a first measurement, beta-emitting 228Ra is obtained via ingrowth of the progeny 228Th on the same sample disc after a standing time of about six months. Calculations are presented for optimizing the analytical accuracy as well as for predicting the sorption yield or chemical recovery of radium on the sample disc as a function of exposure time because the sorption uptake proceeds with first-order kinetics. The analyses can be carried out on small samples of 0.5-11 and, for long counting times of one week and use of high-purity silicon surface barrier detectors, a detection limit of 0.15 mBq l-1 is obtained for 226Ra. Since the half-life of 224Ra is only 3.7 d and since 228Th (as a measure for 228Ra) is built up only partially on the sample disc, a slightly higher detection limit of 0.24 mBq l-1 results for the latter isotopes. The procedure is therefore sufficiently sensitive to allow the investigation of Ra isotope relationships in aquifers at typical environmental levels.

228Ra/226Ra/224Ra and 87Sr/86Sr isotope relationships for determining interactions between ground and river water in the upper Rhine valley.

Ground and river waters of the upper Rhine valley (Alsace, France) were investigated for chemical composition of the major elements, Sr isotopes and radionuclides from the U and Th series. In particular, the isotope ratios and concentrations of Ra and Sr were used as geochemical tracers to distinguish between different types of water and their interactions. The bulk chemical analyses suggest that the surface waters in the Rhine valley can be described as mixtures between Ca-Na-HCO3-rich ground water and less mineralized slightly acidic river waters which have migrated through crystalline (mainly granitic) basement rocks of the Vosges mountains. Mixing of these waters yields positive correlation between bulk Sr, U, Ca and HCO3, indicating that carbonate-rich sediments are the main source of U and (non-radiogenic) Sr in the Rhine valley aquifers. The combination of the Ra and Sr isotope systems (228Ra/226Ra, 87Sr/86Sr) shows, however, that probably three sources contribute to the surface river waters in the upper Rhine valley, i.e. (i) a highly radiogenic crystalline component, (ii) a ground water source and, (iii) a third component from infiltrating Rhine water along the flow path of the parallel running river Ill in the northerly direction. The Sr and Ra isotope systems were also used to calculate small-scale mixing fractions of tributaries along the flow path of the Ill. Mixing ratios of non-pure end-member waters were determined using three isotope diagrams (i.e. 224Ra/226Ra vs. 228Ra/226Ra) and the results obtained with the Ra isotope system were found to be consistent with the data using Sr isotope relationships (i.e. 87Sr/86Sr vs. 1/Sr).