Human papillomavirus negative high grade cervical lesions and cancers: Suggested guidance for HPV testing quality assurance.

BACKGROUND: Some high-grade cervical lesions and cervical cancers (HSIL+) test negative for human papillomavirus (HPV). The HPV-negative fraction varies between 0.03 % and 15 % between different laboratories. Monitoring and extended re-analysis of HPV-negative HSIL+ could thus be helpful to monitor performance of HPV testing services. We aimed to a) provide a real-life example of a quality assurance (QA) program based on re-analysis of HPV-negative HSIL+ and b) develop international guidance for QA of HPV testing services based on standardized identification of apparently HPV-negative HSIL+ and extended re-analysis, either by the primary laboratory or by a national HPV reference laboratory (NRL). METHODS: There were 116 initially HPV-negative cervical specimens (31 histopathology specimens and 85 liquid-based cytology samples) sent to the Swedish HPV Reference Laboratory for re-testing. Based on the results, an international QA guidance was developed through an iterative consensus process. RESULT: Standard PCR testing detected HPV in 55.2 % (64/116) of initially "HPV-negative" samples. Whole genome sequencing of PCR-negative samples identified HPV in an additional 7 samples (overall 61.2 % HPV positivity). Reasons for failure to detect HPV in an HSIL+ lesion are listed and guidance to identify cases for extended re-testing, including which information should be included when referring samples to an NRL are presented. CONCLUSION: Monitoring the proportion of and reasons for failure to detect HPV in HSIL+ will help support high performance and quality improvement of HPV testing services. We encourage implementation of QA strategies based on re-analysis of "HPV negative" HSIL+ samples.

Why, how, and how far should microbiological contamination in a coastal zone be mitigated? An application of the systems approach to the Thau lagoon (France).

This paper describes the building of an integrated simulation tool based on a systems approach, and its contribution to local political discussion of the mitigation of microbiological contamination of the water in a coastal area. Local management schemes view water quality as a high-priority environmental objective. In practice, how far this objective is achieved depends on trade-offs between the costs of improved water treatment facilities and the acceptable impacts of water contamination. An in-the-field experiment in collaboration with local managers was carried out in the Thau lagoon on the French Mediterranean coast during the SPICOSA (Science and Policy Integration for Coastal System Assessment) project, from 2007 through 2011. It consisted of building a modeling platform and an integrated assessment framework for simulating exploratory scenarios. The modeling platform combines a dynamic contamination model, which represents the sources of microbiological contamination, wastewater treatment facilities, and physical mechanisms of lagoon contamination, with a prospective economic model, which estimates the patterns of development of economic activities in the area through a holistic approach. Exploratory scenarios are used to assess the risk of water contamination and the efficiency of management measures, under various assumptions about the evolution of the system. The contamination simulations suggest that the work currently planned by local authorities will be inadequate for preventing increased water pollution, and that additional but fairly inexpensive management measures for maintaining the current level of water quality should be considered. The integrated assessment framework estimates the ecological and socio-economic impacts of the various pollution mitigation policies in the broader context of possible local development patterns. The results illustrate how the systems approach may aid in the design of an applicable water policy based on operational objectives and feasible technical options.

Reducing PEC uncertainty in coastal zones: a case study on carbamazepine, oxcarbazepine and their metabolites.

Concentrations of the antiepileptic drugs carbamazepine (Cbz), oxcarbazepine (OxCz) and their main metabolites were predicted in a wastewater treatment plant (WTP) and in the vicinity of its submarine outfall located in a Mediterranean coastal zone. Refined predicted environmental concentrations (PECs) were calculated in effluents based on consumption data and human excretion rates. PECs were estimated in the sea using the hydrodynamic MARS 3D model integrating meteorological data, oceanic conditions (wind, tide, atmospheric pressure), freshwater and sewage inputs. Measured environmental concentrations (MECs) were compared to PECs to assess the estimation relevance. In the coastal zone, PEC and MEC were in the same magnitude range. Modeling of Cbz diffusion and advection just above the submarine outfall showed the influence of the thermocline during summer, with low diffusion of Cbz from the bottom to the surface. This work allowed understanding the dispersion of target compounds and deserved further development for a better acknowledgement of vulnerability at local scales.