5 research outputs found
Quality assurance of human papillomavirus (HPV) testing in the implementation of HPV primary screening in Norway: an inter-laboratory reproducibility study
Prognostic impact of chromosomal aberrations and GNAQ, GNA11 and BAP1 mutations in uveal melanoma
Quality assurance of human papillomavirus (HPV) testing in the implementation of HPV primary screening in Norway: an inter-laboratory reproducibility study
Abstract Background Human papillomavirus (HPV) testing as primary screening for cervical cancer is currently being implemented in Norway in a randomized controlled fashion, involving three laboratories. As part of the quality assurance programme of the implementation, an evaluation of the inter-laboratory reproducibility of the HPV test was initiated, to ensure satisfactory HPV test reliability in all three laboratories. Methods The HPV test used is the cobas 4800 HPV Test, detecting 14 high-risk types with individual HPV genotype results for HPV16 and HPV18. In addition to the three laboratories involved in the implementation, the Norwegian HPV reference laboratory was included as a fourth comparative laboratory. A stratified sample of 500 cervical liquid based cytology (LBC) samples was used in the evaluation, with an aim towards a high-risk HPV positivity of ~25%. Samples were collected at one laboratory, anonymized, aliquoted, and distributed to the other laboratories. Results Comparison of the test results of all four laboratories revealed a 95.6% agreement, an 86.3% positive agreement and a kappa value of 0.94 (95% CI 0.92–0.97). For negative cytology specimens, there was a 95.8% overall agreement, a 67.4% positive agreement, and a kappa value of 0.88 (95% CI 0.80–0.93). For abnormal cytology specimens, there was a 95.8% overall agreement, a 95.5% positive agreement, and a kappa value of 0.86 (95% CI 0.71–0.97). Conclusions The study showed a high inter-laboratory reproducibility of HPV testing, implying satisfactory user performance and reliability in the laboratories involved in the implementation project. This is important knowledge and we recommend similar studies always to be performed prior to the introduction of new screening routines
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The genomic landscape and evolution of endometrial carcinoma progression and abdominopelvic metastasis
Recent studies have detailed the genomic landscape of primary endometrial cancers, but their evolution into metastases has not been characterized. We performed whole-exome sequencing of 98 tumor biopsies including complex atypical hyperplasias, primary tumors, and paired abdominopelvic metastases to survey the evolutionary landscape of endometrial cancer. We expanded and reanalyzed TCGA-data, identifying novel recurrent alterations in primary tumors, including mutations in the estrogen receptor cofactor NRIP1 in 12% of patients. We found that likely driver events tended to be shared by primary and metastatic tissue-samples, with notable exceptions such as ARID1A mutations. Phylogenetic analyses indicated that the sampled metastases typically arose from a common ancestral subclone that was not detected in the primary tumor biopsy. These data demonstrate extensive genetic heterogeneity within endometrial cancers and relative homogeneity across metastatic sites