CIN2+ detection of the HPV DNA Array genotyping assay in comparison with the Cobas 4800 HPV test and cytology

BACKGROUND: HPV DNA Array is an E1-targeting PCR genotyping test, with capability of distinguishing 18 high-risk (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82) and 11 low-risk HPV types (6, 11, 40, 42, 44, 54, 67, 69, 70, 85, 97). HPV DNA Array uses multiplex PCR for E1-gene sequence amplification. The amplicons are detected and genotyped by reverse hybridization to immobilized DNA probes spotted as triplets in single 96 well-plate wells and read by AID ELISPOT reader. METHODS: Aim of the study was to evaluate the clinical performance of the assay against internationally accepted and FDA approved Cobas 4800 HPV test (Roche Diagnostics). Study population comprised of 500 cervical samples. RESULTS: HPV DNA Array demonstrated a very high sensitivity of 100% for CIN2+ and 100% for CIN3+ detection, same as Cobas 4800. HPV DNA Array showed greater sensitivity for CIN2+ detection than cytology (100% vs. 13.6%). The agreement to Cobas 4800 for HPV detection, irrespective of type, was 81.4% with κ = 0.613. The agreement for HPV 16 was 92.8% (κ = 0.929), and for HPV 18 54.2% (κ = 0.681). CONCLUSION: HPV DNA Array demonstrated good clinical performance for detection of high-grade lesions, and may be considered for usage in a screening setting

Semantic Integration of Cervical Cancer Data Repositories to Facilitate Multicenter Association Studies: The ASSIST Approach

The current work addresses the unifi cation of Electronic Health Records related to cervical cancer into a single medical knowledge source, in the context of the EU-funded ASSIST research project. The project aims to facilitate the research for cervical precancer and cancer through a system that virtually unifi es multiple patient record repositories, physically located in different medical centers/hospitals, thus, increasing fl exibility by allowing the formation of study groups “on demand” and by recycling patient records in new studies. To this end, ASSIST uses semantic technologies to translate all medical entities (such as patient examination results, history, habits, genetic profi le) and represent them in a common form, encoded in the ASSIST Cervical Cancer Ontology. The current paper presents the knowledge elicitation approach followed, towards the defi nition and representation of the disease’s medical concepts and rules that constitute the basis for the ASSIST Cervical Cancer Ontology. The proposed approach constitutes a paradigm for semantic integration of heterogeneous clinical data that may be applicable to other biomedical application domains

Genetic polymorphisms of FAS and EVER genes in a Greek population and their susceptibility to cervical cancer : a case control study

Ajuts: the present study was developed on a self-funding base, using a personal budget of Evangelia Pavlidou for the reagents used in the laboratory analysis.Background: the aim of the study was to evaluate the association of two SNPs of EVER1/2 genes' region (rs2290907, rs16970849) and the FAS-670 polymorphism with the susceptibility to precancerous lesions and cervical cancer in a Greek population. -Methods: among the 515 women who were included in the statistical analysis, 113 belong to the case group and present with precancerous lesions or cervical cancer (27 with persistent CIN1, 66 with CIN2/3 and 20 with cervical cancer) and 402 belong to the control group. The chi-squared test was used to compare the case and the control groups with an allelic and a genotype-based analysis. - Results: the results of the statistical analysis comparing the case and the control groups for all the SNPs tested were not statistically significant. Borderline significant difference (p value = 0.079) was only found by the allelic model between the control group and the CIN1/CIN2 patients' subgroup for the polymorphism rs16970849. The comparison of the other case subgroups with the control group did not show any statistically significant difference. Conclusions: None of the SNPs included in the study can be associated with statistical significance with the development of precancerous lesions or cervical cancer

Semantic Integration of Cervical Cancer Data Repositories to Facilitate Multicenter Association Studies: The ASSIST Approach

The current work addresses the unification of Electronic Health Records related to cervical cancer into a single medical knowledge source, in the context of the EU-funded ASSIST research project. The project aims to facilitate the research for cervical precancer and cancer through a system that virtually unifies multiple patient record repositories, physically located in different medical centers/hospitals, thus, increasing flexibility by allowing the formation of study groups “on demand” and by recycling patient records in new studies. To this end, ASSIST uses semantic technologies to translate all medical entities (such as patient examination results, history, habits, genetic profile) and represent them in a common form, encoded in the ASSIST Cervical Cancer Ontology. The current paper presents the knowledge elicitation approach followed, towards the definition and representation of the disease’s medical concepts and rules that constitute the basis for the ASSIST Cervical Cancer Ontology. The proposed approach constitutes a paradigm for semantic integration of heterogeneous clinical data that may be applicable to other biomedical application domains

High risk HPV-positive women cervicovaginal microbial profiles in a Greek cohort: a retrospective analysis of the GRECOSELF study

Increasing evidence supports a role for the vaginal microbiome (VM) in the severity of HPV infection and its potential link to cervical intraepithelial neoplasia. However, a lot remains unclear regarding the precise role of certain bacteria in the context of HPV positivity and persistence of infection. Here, using next generation sequencing (NGS), we comprehensively profiled the VM in a series of 877 women who tested positive for at least one high risk HPV (hrHPV) type with the COBAS® 4,800 assay, after self-collection of a cervico-vaginal sample. Starting from gDNA, we PCR amplified the V3–V4 region of the bacterial 16S rRNA gene and applied a paired-end NGS protocol (Illumina). We report significant differences in the abundance of certain bacteria compared among different HPV-types, more particularly concerning species assigned to Lacticaseibacillus, Megasphaera and Sneathia genera. Especially for Lacticaseibacillus, we observed significant depletion in the case of HPV16, HPV18 versus hrHPVother. Overall, our results suggest that the presence or absence of specific cervicovaginal microbial genera may be linked to the observed severity in hrHPV infection, particularly in the case of HPV16, 18 types

Economic evaluation of HPV DNA test as primary screening method for cervical cancer: A health policy discussion in Greece

Background HPV test appears to be more effective in cervical cancer (CC) screening. However, the decision of its adoption as a primary screening method by substituting the established cytology lies in the evaluation of multiple criteria. Aim of this study is to evaluate the economic and clinical impact of HPV test as primary screening method for CC. Methods A decision tree and a Markov model were developed to simulate the screening algorithm and the natural history of CC. Fourteen different screening strategies were evaluated, for women 25-65 years old. Clinical inputs were drawn from the HERMES study and cost inputs from the official price lists. In the absence of CC treatment cost data, the respective Spanish costs were used after being converted to 2017 Greek values. One-way and probabilistic sensitivity analyses were conducted. Results All screening strategies, that offer as primary screening method triennial HPV genotyping (simultaneous or reflex) alone or as co-testing with cytology appear to be more effective than all other strategies, with regards to both annual CC mortality, due to missed disease (-10.1), and CC incidence(-7.5) versus annual cytology (current practice). Of those, the strategy with HPV test with simultaneous 16/18 genotyping is the strategy that provides savings of 1.050 million euros annually. However, when the above strategy is offered quinquennially despite the fact that outcomes are decreased it remains more effective than current practice (-7.7 deaths and -1.3 incidence) and more savings per death averted (1.323 million) or incidence reduced (7.837 million) are realized. Conclusions HPV 16/18 genotyping as a primary screening method for CC appears to be one of the most effective strategies and dominates current practice in respect to both cost and outcomes. Even when compared with all other strategies, the outcomes that it generates justify the cost that it requires, representing a good value for money alternative

Economic evaluation of HPV DNA test as primary screening method for cervical cancer: A health policy discussion in Greece.

BACKGROUND:HPV test appears to be more effective in cervical cancer (CC) screening. However, the decision of its adoption as a primary screening method by substituting the established cytology lies in the evaluation of multiple criteria. Aim of this study is to evaluate the economic and clinical impact of HPV test as primary screening method for CC. METHODS:A decision tree and a Markov model were developed to simulate the screening algorithm and the natural history of CC. Fourteen different screening strategies were evaluated, for women 25-65 years old. Clinical inputs were drawn from the HERMES study and cost inputs from the official price lists. In the absence of CC treatment cost data, the respective Spanish costs were used after being converted to 2017 Greek values. One-way and probabilistic sensitivity analyses were conducted. RESULTS:All screening strategies, that offer as primary screening method triennial HPV genotyping (simultaneous or reflex) alone or as co-testing with cytology appear to be more effective than all other strategies, with regards to both annual CC mortality, due to missed disease (-10.1), and CC incidence(-7.5) versus annual cytology (current practice). Of those, the strategy with HPV test with simultaneous 16/18 genotyping is the strategy that provides savings of 1.050 million euros annually. However, when the above strategy is offered quinquennially despite the fact that outcomes are decreased it remains more effective than current practice (-7.7 deaths and -1.3 incidence) and more savings per death averted (1.323 million) or incidence reduced (7.837 million) are realized. CONCLUSIONS:HPV 16/18 genotyping as a primary screening method for CC appears to be one of the most effective strategies and dominates current practice in respect to both cost and outcomes. Even when compared with all other strategies, the outcomes that it generates justify the cost that it requires, representing a good value for money alternative