Study-based evaluation of the Abbott RealTime High Risk HPV test in comparison to the HC2 HR HPV test in women aged ≥30 years using residual LBC ThinPrep specimens.

BACKGROUND: High-risk human papillomavirus (HR HPV) testing is already part of cervical cancer screening programs in a number of countries. New tests need to be validated not only in clinical studies but also in routine screening settings with regard to their clinical performance. METHODS: The Abbott RealTime High Risk HPV Test (RT hrHPV test) was evaluated in a random sample of 1,456 patients from a German routine screening population of 13,372 women ≥30 years of age screened primarily by liquid-based cytology (LBC) that was complemented by 48 CIN3+ cases. Clinical sensitivities, relative specificities and positive predictive values (PPV) for both HPV tests were determined based on histologically confirmed high-grade cervical disease (CIN3+) as clinical outcome. RESULTS: HR HPV prevalence in residual LBC samples was found to be 5.4 % by the RT hrHPV test and 5.6 % by the HR HC2 test, respectively. The Kappa-value for overall agreement between the RT hrHPV test and the HC2 assay for detection of HR HPV was 0.87. Relative sensitivities for detection of CIN3+ in patients with abnormal cytology was 93.8 % for the RT hrHPV assay and 97.9 % for HC2 (p-value = 0.5). Relative specificities and PPVs were comparable for both tests. The highest PPV was calculated for the specific detection of HPV16 by the RT hrHPV test (84.2 %). The RT hrHPV test showed a reduced sensitivity for detection of HVP31-positive CIN3 + . CONCLUSION: The RT hrHPV assay is as sensitive and specific in detecting severe cervical lesions in women with abnormal cytology as the HC2 HR HPV test.

Utility of EFC quality indicators for colposcopy in daily practice: results from an independent, prospective multicenter trial.

OBJECTIVES: The accuracy of colposcopy as the gold standard to manage abnormal screening tests depends on qualification and well defined standards. A recent survey of the European Federation for Colposcopy (EFC) found strong heterogeneity in the practice of colposcopy across Europe. EFC defined four quality indicators (QIs) to enable quality assessment in colposcopy as one tool to harmonize colposcopy standards. We undertook a pilot project to estimate the utility of these QIs for an independent external quality assessment in daily routine colposcopy. STUDY DESIGN: Participating colposcopy clinics used newly developed software for data collection. Data were automatically anonymized, encrypted and stored in a secure relational database located within the clinics' network and allowed for an independent external benchmarking comparing the performance of participating clinics according to EFC QIs. RESULTS: 10,869 patients referred for routine colposcopy were included. On average none of the four EFC QIs was fulfilled. One target was almost met with 83.3% instead of 85% excisional treatments/conizations containing CIN2+ and for another QI the difference of 94.4% instead of 100% cases having a colposcopic examination prior to treatment for abnormal cervical cytology was mainly explained by wrong documentation. For a third QI, visibility of the squamocolumnar junction (SCJ) was only reported in 90.9% instead of 100% but reporting improved to 94.7% after a consensus meeting. The last QI, >80% clear margins in excised lesions/conizations were not considered as useful by some clinics and therefore not documented. DISCUSSION AND CONCLUSIONS: At least 3 out of 4 QIs seemed to be useful for quality assessment in colposcopy but will need rewording and readjustment. All tools for an independent electronic quality assessment with the use of EFC-QI are available and could be used to achieve a high quality standard in colposcopy across Europe.

Utility and Reproducibility of the International Federation for Cervical Pathology and Colposcopy Classification of Transformation Zones in Daily Practice: A Multicenter Study of the German Colposcopy Network.

OBJECTIVE: To compare the distribution of International Federation for Cervical Pathology and Colposcopy (IFCPC) transformation zone (TZ) types among women in different age groups referred to 8 colposcopy clinics. MATERIALS AND METHODS: Between February 2012 and February 2013, we prospectively collected individual patient data from 8 clinics within the German Colposcopy Network (G-CONE). Data were analyzed using ODSdysplasie, software designed to allow continuous quality assessment in colposcopy clinics. The distribution of IFCPC-classified TZ was compared between different centers for the following age groups: younger than 30 years, between 30 and 50 years, and older than 50 years. RESULTS: Of 3,761 patients included in the analysis, 2,153 (57%) were classified as having type 2 TZ, 906 (24%) as type 1 TZ, and 702 (19%) as type 3 TZ. Type 3 TZ was the most commonly reported type in women older than 50 years (70%). We found that the relative distribution of type 3 TZ between age groups was similar in the participating colposcopy clinics. However, there was evidence of heterogeneous distribution of types 1 and 2 TZ between age groups in different clinics, ranging from 7.8% to 66.4% for type 1 TZ in women younger than 30 years and 28.9% to 78.1% for type 2 TZ in women 30 to 50 years old. CONCLUSIONS: Although IFCPC type 3 TZ seems to be a reproducible finding, the distribution of types 1 and 2 TZ showed significant heterogeneity. A more precise anatomic distinction between types 1 and 2 TZ in the IFCPC terminology could improve reporting of colposcopy findings.

A population-based observational study comparing Cervista and Hybrid Capture 2 methods: improved relative specificity of the Cervista assay by increasing its cut-off.

BACKGROUND: High-risk human papillomavirus (HR HPV) testing has been shown to be a valuable tool in cervical cancer screening for the detection of cervical pre-cancer and cancer. METHODS: We report a purely observational study evaluating HR HPV prevalences in residual liquid-based cytology (LBC) samples using both the Cervista™ HPV HR Test and the Digene Hybrid Capture 2 High-Risk HPV DNA Test (HC2) in a sample of 1,741 women aged ≥30 years of a German routine screening population of 13,372 women. Test characteristics were calculated and a novel method for measuring test performances was applied by calculating ratios of sensitivity or specificity. RESULTS: The overall agreement of both tests for detection of HR HPV was excellent (κ = 0.8). Relative sensitivities for the detection of histologically confirmed severe cervical intraepithelial dysplasia (CIN3+) were similar for both HPV-tests, which was confirmed by the ratio analysis. However, discrepancy analysis between the Cervista HPV HR test and HC2 revealed a high false positive rate of the Cervista HPV HR test in the cytology normal category. CONCLUSIONS: Performance of the Cervista HPV test in cervical specimens with abnormal cytology is comparable to HC2 as both tests were highly sensitive and specific for the detection of high grade cervical disease. We also demonstrate evidence that modification of the cut-off values drastically reduces the false positive rate in the cytology normal category without affecting the detection of CIN3+, which ultimately improved specificity of the Cervista HPV HR assay.

Platelet-activating factor contributes to the induction of long-term potentiation in the rat somatosensory cortex in vitro.

The contribution of platelet-activating factor (PAF) to the induction of neocortical LTP was examined in rat brain slices containing the primary somatosensory cortex (SI). Field potentials evoked by single pulse stimulation in cortical layer IV were recorded from layer II/III. In control experiments, tetanic high frequency stimulation (HFS) resulted in input-specific, NMDA receptor-dependent LTP (21.1+/-3.2%; mean+/-SEM; n=15; P<0.001). BN-52021 (5 microM), an antagonist at the extracellular PAF receptor, weakened the HFS-induced LTP to 12.4+/-2.7% (n=11; P<0.05). In contrast, HFS-induced LTP was significantly enhanced to 29.4+/-2.3% (n=11; P<0.05) when brain slices were superfused with ACSF containing the PAF receptor-agonist C-PAF (1.5 microM). The difference between LTP weakened by BN-52021 and LTP enhanced by C-PAF was highly significant (P<0.0005). These results suggest a physiological contribution of PAF to the induction of LTP in neocortical area SI. This contribution of PAF is mediated by an action at extracellular receptor sites.

The superoxide anion is involved in the induction of long-term potentiation in the rat somatosensory cortex in vitro.

The involvement of the superoxide anion (O2-) in the induction of neocortical long-term potentiation (LTP) was examined in rat brain slices containing the primary somatosensory cortex. Field potentials evoked by stimulation in cortical layer IV were recorded from layer II/III. In control experiments, tetanic high-frequency stimulation (HFS) resulted in essentially input-specific, NMDA receptor-dependent LTP (20.2+/-3.0% increase in field potential amplitude). When the availability of intracellular O2- was reduced by application of the cell membrane-permeable O2- scavengers MnTBAP or CP-H (spin trap), HFS-induced LTP was attenuated to 12.0+/-1.7% and 8.7+/-3.1% increase, respectively. In contrast, HFS-induced LTP was not significantly affected by the cell membrane-impermeable O2- scavenger superoxide dismutase (SOD). Induction of the generation of O2- by the cell membrane-permeable redox-cycling quinone DMNQ resulted in a HFS-independent slow-onset LTP (21.8+/-6.0%) in three of eight brain slices. Together, these results suggest the contribution of O2- to the induction of LTP in the primary somatosensory cortex by an action on intracellular induction mechanisms.