Moving towards a reliable HIV incidence test - current status, resources available, future directions and challenges ahead.

In 2011 the Incidence Assay Critical Path Working Group reviewed the current state of HIV incidence assays and helped to determine a critical path to the introduction of an HIV incidence assay. At that time the Consortium for Evaluation and Performance of HIV Incidence Assays (CEPHIA) was formed to spur progress and raise standards among assay developers, scientists and laboratories involved in HIV incidence measurement and to structure and conduct a direct independent comparative evaluation of the performance of 10 existing HIV incidence assays, to be considered singly and in combinations as recent infection test algorithms. In this paper we report on a new framework for HIV incidence assay evaluation that has emerged from this effort over the past 5 years, which includes a preliminary target product profile for an incidence assay, a consensus around key performance metrics along with analytical tools and deployment of a standardized approach for incidence assay evaluation. The specimen panels for this evaluation have been collected in large volumes, characterized using a novel approach for infection dating rules and assembled into panels designed to assess the impact of important sources of measurement error with incidence assays such as viral subtype, elite host control of viraemia and antiretroviral treatment. We present the specific rationale for several of these innovations, and discuss important resources for assay developers and researchers that have recently become available. Finally, we summarize the key remaining steps on the path to development and implementation of reliable assays for monitoring HIV incidence at a population level.

Upgrading of Gleason score 6 prostate cancers on biopsy after prostatectomy in the low and intermediate tPSA range.

When offering watchful waiting or active monitoring protocols to prostate cancer (PCa) patients, differentiation between Gleason scores (GS) 6 and 7 at biopsy is important. However, upgrading after prostatectomy is common. We investigated the impact of different PSA levels on misclassification in the PSA range of 2-3.9 and 4-10 ng ml(-1). A total of 448 patients with GS 6 PCa on prostate biopsy were evaluated by comparing biopsy and prostatectomy GS. Possible over diagnosis was defined as GS <7, pathological stage pT2a and negative surgical margins, and possible under diagnosis was defined as pT3a or greater, or positive surgical margins; the percentage of over- or under diagnosis was determined for correctly and upgraded tumors after prostatectomy. A match between biopsy and prostatectomy GS was found in 210 patients (46.9%). Patients in the PSA range of 2.0-3.9 and 4.0-10.0 ng ml(-1) were upgraded in 32.6 and 44.0%, respectively. Over diagnosis was more common than under diagnosis (23.2% vs 15.6%). When upgraded there was a significant increase in under diagnosis. As almost 40% of GS 6 tumors on biopsy are GS 7 or higher after surgery with a significant rise in under diagnosis there is a risk of misclassification and subsequent delayed or even insufficient treatment, when relying on favorable biopsy GS.

Ovarian cancer identification based on dimensionality reduction for high-throughput mass spectrometry data.

MOTIVATION: High-throughput and high-resolution mass spectrometry instruments are increasingly used for disease classification and therapeutic guidance. However, the analysis of immense amount of data poses considerable challenges. We have therefore developed a novel method for dimensionality reduction and tested on a published ovarian high-resolution SELDI-TOF dataset. RESULTS: We have developed a four-step strategy for data preprocessing based on: (1) binning, (2) Kolmogorov-Smirnov test, (3) restriction of coefficient of variation and (4) wavelet analysis. Subsequently, support vector machines were used for classification. The developed method achieves an average sensitivity of 97.38% (sd = 0.0125) and an average specificity of 93.30% (sd = 0.0174) in 1000 independent k-fold cross-validations, where k = 2, ..., 10. AVAILABILITY: The software is available for academic and non-commercial institutions.