Assessment of attribution algorithms for resolving CIN3-related HPV genotype prevalence in mixed-genotype biopsy specimens using laser capture microdissection as the reference standard.

To make accurate determinations regarding potential and actual impact of HPV vaccine programs, precise estimates of genotype-specific contributions to disease are required for pre- and post-vaccine populations. Definitive determination of lesion-specific genotypes, particularly where multiple genotypes are detected in a sample, can be technically demanding and resource intensive; therefore, most prevalence studies use mathematical algorithms to adjust for multiple genotype detections. There are currently several algorithms, which can produce genotype estimates within a wide range of variability. The use of these for cervical cytology samples has recently been assessed for accuracy against a definitive reference standard, but none have yet been assessed for multiple-genotype-containing whole biopsy specimens. Using laser capture microdissection (LCM) on biopsy samples, lesion-specific genotype prevalence data were generated for a cohort of 516 young Australian women (aged 18-32 years) with cervical intraepithelial neoplasia grade 3 or adenocarcinoma in situ. Using whole tissue section genotype data from the same cohort, including 71 (13.7%) with multiple genotypes, lesion-associated genotype prevalence was estimated using four different attribution algorithms. The proportion of lesions attributable to HPV16 and HPV18 by LCM were 58.4% and 5%, respectively; hierarchical, proportional, single type/minimum and any type/maximum attribution estimates were comparable across genotypes. For analyses utilising whole tissue biopsy cervical specimens, attribution estimates are appropriate for estimating the proportional contribution of individual genotypes to lesions in a population.

Quality and Equity in Wheelchairs Used by Veterans.

OBJECTIVES: To assess in Veterans with spinal cord injury (SCI) or amputated limb (AL) the following: (1) patient demographics, medical factors, cultural and psychosocial characteristic by race; (2) wheelchair quality by race; and (3) the independent associations of patient race and the other factors with wheelchair quality. DESIGN: Cross-sectional cohort study. SETTING: Three Department of Veterans Affairs (VA) medical centers affiliated with academic medical centers. PARTICIPANTS: Eligible participants were Veterans with SCI or ALs (N=516); 482 of them completed the interview. Analyses were restricted to white and African American participants. Because there was no variation in wheelchair quality among AL patients (n=42), they were excluded from all but descriptive analyses, leading to a final sample size of 421. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Wheelchair quality as defined by the Medicare Healthcare Common Procedure Coding System. RESULTS: We found race differences in many of our variables, but not in quality for manual (odds ratio [OR]=.67; 95% confidence interval [CI], .33-1.36) or power (OR=.82; 95% CI, .51-1.34) wheelchairs. Several factors including age (OR=.96; 95% CI, .93-.99) and income (OR=3.78; 95% CI, 1.43-9.97) were associated with wheelchair quality. There were no significant associations of cultural or psychosocial factors with wheelchair quality. CONCLUSIONS: Although there were no racial differences in wheelchair quality, we found a significant association of older age and lower income with poorer wheelchair quality among Veterans. Efforts are needed to raise awareness of such disparities among VA wheelchair providers and to take steps to eliminate these disparities in prescription practice across VA sites.

Characterization of the ecological interactions of Roundup Ready 2 Yield® soybean, MON 89788, for use in ecological risk assessment.

As part of an ecological risk assessment, Roundup Ready 2 Yield® soybean (MON 89788) was compared to a conventional control soybean variety, A3244, for disease and arthropod damage, plant response to abiotic stress and cold, effects on succeeding plant growth (allelopathic effects), plant response to a bacterial symbiont, and effects on the ability of seed to survive and volunteer in a subsequent growing season. Statistically significant differences between MON 89788 and A3244 were considered in the context of the genetic variation known to occur in soybean and were assessed for their potential impact on plant pest (weed) potential and adverse environmental impact. The results of these studies revealed no effects of the genetic modification that would result in increased pest potential or adverse environmental impact of MON 89788 compared with A3244. This paper illustrates how such characterization studies conducted in a range of environments where the crop is grown are used in an ecological risk assessment of the genetically modified (GM) crop. Furthermore, risk assessors and decision makers use this information when deciding whether to approve a GM crop for cultivation in-or grain import into-their country.

Plant characterization of Roundup Ready 2 Yield ® soybean, MON 89788, for use in ecological risk assessment.

During the development of a genetically modified (GM) crop product, extensive phenotypic and agronomic data are collected to characterize the plant in comparison to a conventional control with a similar genetic background. The data are evaluated for potential differences resulting from the genetic modification process or the GM trait, and the differences--if any--are subsequently considered in the context of contributing to the pest potential of the GM crop. Ultimately, these study results and those of other studies are used in an ecological risk assessment of the GM crop. In the studies reported here, seed germination, vegetative and reproductive growth, and pollen morphology of Roundup Ready 2 Yield(®) soybean, MON 89788, were compared to those of A3244, a conventional control soybean variety with the same genetic background. Any statistically significant differences were considered in the context of the genetic variation known to occur in soybean and were evaluated as indicators of an effect of the genetic modification process and assessed for impact on plant pest (weed) characteristics and adverse ecological impact (ecological risk). The results of these studies revealed no effects attributable to the genetic modification process or to the GM trait in the plant that would result in increased pest potential or adverse ecological impact of MON 89788 compared with A3244. These results and the associated risk assessments obtained from diverse geographic and environmental conditions in the United States and Argentina can be used by regulators in other countries to inform various assessments of ecological risk.

In vitro assessment of the effect of vaccine-targeted human papillomavirus (HPV) depletion on detection of non-vaccine HPV types: implications for post-vaccine surveillance studies.

In populations where the prevalence of vaccine-targeted HPV types has been reduced significantly due to widespread vaccination of the target population, the sensitivity of some consensus PCR-based assays to detect remaining HPV types may be altered, leading to misrepresentations of prevalence. Importantly, this may lead to false indications of type replacement in vaccinated populations. To assess whether excess vaccine-targeted HPV DNA resulted in reduced detection of other genotypes on the Roche HPV linear array genotype assay, simulated samples containing 1000 copies of one or two high-risk HPV DNA genomes in the presence and the absence of 10,000 copies of the HPV16 genome were tested. HPV16 alone did not affect detection of other high-risk genotypes; however when HPV16 and an additional genotype were present, detection of HPV31, 33, 51 or 59 was impeded, indicating potential for misrepresentation of population-based prevalence of these genotypes and false evidence for type replacement following vaccination.

Assessment of herd immunity and cross-protection after a human papillomavirus vaccination programme in Australia: a repeat cross-sectional study.

BACKGROUND: After the introduction of a quadrivalent human papillomavirus (HPV) vaccination programme in Australia in April, 2007, we measured the prevalence of vaccine-targeted and closely related HPV types with the aim of assessing direct protection, cross-protection, and herd immunity. METHODS: In this repeat cross-sectional study, we recruited women aged 18-24 years who attended Pap screening between October, 2005, and July, 2007, in three major metropolitan areas of Australia to form our prevaccine-implementation sample. For our postvaccine-implementation sample, we recruited women aged 18-24 years who attended Pap screening in the same three metropolitan areas from August, 2010, to November, 2012. We compared the crude prevalence of HPV genotypes in cervical specimens between the prevaccine and the postvaccine implementation groups, with vaccination status validated against the National HPV Vaccination Program Register. We estimated adjusted prevalence ratios using log linear regression. We estimated vaccine effectiveness both for vaccine-targeted HPV types (16, 18, 6, and 11) and non-vaccine but related HPV types (31, 33, and 45). FINDINGS: 202 women were recruited into the prevaccine-implementation group, and 1058 were recruited into the postvaccine-implementation group. Crude prevalence of vaccine-targeted HPV genotypes was significantly lower in the postvaccine-implementation sample than in the prevaccine-implementation sample (58 [29%] of 202 vs 69 [7%] of 1058; p<0·0001). Compared with the prevaccine-implementation sample, adjusted prevalence ratios for vaccine-targeted HPV genotypes were 0·07 (95% CI 0·04-0·14; p<0·0001) in fully vaccinated women and 0·65 (0·43-0·96; p=0·03) in unvaccinated women, which suggests herd immunity. No significant declines were noted for non-vaccine-targeted HPV genotypes. However, within the postvaccine-implementation sample, adjusted vaccine effectiveness against vaccine-targeted HPV types for fully vaccinated women compared with unvaccinated women was 86% (95% CI 71-93), and was 58% (26-76) against non-vaccine-targeted but related genotypes (HPV 31, 33, and 45). INTERPRETATION: 6 years after the initiation of the Australian HPV vaccination programme, we have detected a substantial fall in vaccine-targeted HPV genotypes in vaccinated women; a lower prevalence of vaccine-targeted types in unvaccinated women, suggesting herd immunity; and a possible indication of cross-protection against HPV types related to the vaccine-targeted types in vaccinated women. FUNDING: Australian National Health and Medical Research Council and Cancer Council Victoria.