Evaluation of Integrated HPV DNA as Individualized Biomarkers for the Detection of Recurrent CIN2/3 during Post-Treatment Surveillance.

PURPOSE: Post-treatment follow-up in women with cervical pre-cancers (CIN3) is mandatory due to relapse in up to 10% of patients. Standard follow-up based on hrHPV-DNA/cytology co-testing has high sensitivity but limited specificity. The aim of our prospective, multicenter, observational study was to test the hypothesis that an individualized viral-cellular-junction test (vcj-PCR) combined with cytology has a lower false positive rate for the prediction of recurrence compared to standard co-testing. METHODS: Pre-surgical cervical swabs served for the identification of HPV16/18 DNA integration sites by next-generation-sequencing (NGS). Samples taken at 6, 12 and 24 months post-surgery were evaluated by cytology, hrHPV-DNA and the patients' individual HPV-integration sites (vcj-PCR on the basis of NGS). RESULTS: Integration sites were detected in 48 of 445 patients (10.8%), 39 of them had valid follow-up data. The false positive rate was 18.2% (95% CI 8.6-34.4%) for standard hrHPV/cytology at six months compared to 12.1% (95% CI 4.8-27.3%) for vcj-PCR/cytology, respectively (McNemar p = 0.50). Six patients developed recurrences (1 CIN2, 5 CIN3) during follow-up. Standard co-testing detected all, whereas vcj-PCR/cytology detected only five patients with recurrences. Data of 269 patients without evidence of HPV16/18 integration were subject to post-hoc analyses. Standard co-testing revealed a false positive rate of 15.7% (95% CI 11.7-20.7%) and predicted ten of fourteen recurrences at six months. CONCLUSIONS: Although highly specific on its own vcj-PCR could not detect all recurrent CIN2/3. Possible reasons for this unexpected result may be multifocal lesions, intratumoral heterogeneity with respect to HPV integration and/or incident CIN.

p-BioSPRE-an information and communication technology framework for transnational biomaterial sharing and access.

Biobanks represent key resources for clinico-genomic research and are needed to pave the way to personalised medicine. To achieve this goal, it is crucial that scientists can securely access and share high-quality biomaterial and related data. Therefore, there is a growing interest in integrating biobanks into larger biomedical information and communication technology (ICT) infrastructures. The European project p-medicine is currently building an innovative ICT infrastructure to meet this need. This platform provides tools and services for conducting research and clinical trials in personalised medicine. In this paper, we describe one of its main components, the biobank access framework p-BioSPRE (p-medicine Biospecimen Search and Project Request Engine). This generic framework enables and simplifies access to existing biobanks, but also to offer own biomaterial collections to research communities, and to manage biobank specimens and related clinical data over the ObTiMA Trial Biomaterial Manager. p-BioSPRE takes into consideration all relevant ethical and legal standards, e.g., safeguarding donors' personal rights and enabling biobanks to keep control over the donated material and related data. The framework thus enables secure sharing of biomaterial within open and closed research communities, while flexibly integrating related clinical and omics data. Although the development of the framework is mainly driven by user scenarios from the cancer domain, in this case, acute lymphoblastic leukaemia and Wilms tumour, it can be extended to further disease entities.

Safeguarding donors' personal rights and biobank autonomy in biobank networks: the CRIP privacy regime.

Governance, underlying general ICT (Information and Communication Technology) architecture, and workflow of the Central Research Infrastructure for molecular Pathology (CRIP) are discussed as a model enabling biobank networks to form operational "meta biobanks" whilst respecting the donors' privacy, biobank autonomy and confidentiality, and the researchers' needs for appropriate biospecimens and information, as well as confidentiality. Tailored to these needs, CRIP efficiently accelerates and facilitates research with human biospecimens and data.

Development and perspectives of scientific services offered by genomic biological resource centres.

A number of fundamental technical developments like the evolvement of oligonucleotide microarrays, new sequencing technologies and gene synthesis have considerably changed the character of genomic biological resource centres in recent years. While genomic biological resource centres traditionally served mainly as providers of sparsely characterized cDNA clones and clone sets, there is nowadays a clear tendency towards well-characterized, high-quality clones. In addition, major new service units like microarray services have developed, which are completely independent of clone collections, reflecting the co-evolution of data generation and technology development. The new technologies require an increasingly higher degree of specialization, data integration and quality standards. Altogether, these developments result in spin-offs of highly specialized biotech companies, some of which will take a prominent position in translational medicine.