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Infectious Agents and Cancer 2020Genital infection with certain types of Human papillomavirus (HPV) is a major cause of cervical cancer globally. For early detection of premalignant dysplasia, evidences... (Review)
Review
BACKGROUND
Genital infection with certain types of Human papillomavirus (HPV) is a major cause of cervical cancer globally. For early detection of premalignant dysplasia, evidences are coming out on the usefulness of HPV E6/E7 mRNA test as a potential tool compared with cytology and HPV DNA testing. Taking into account shortage of compiled data on this field, the aim of this systematic review was to describe the latest diagnostic performance of HPV E6/E7 mRNA testing to detect high grade cervical lesions (CIN2+) where by histology was taken as a gold standard.
METHODS
Articles published in English were systematically searched using key words from PubMed/Medline and SCOPUS. In addition, Google Scholar and the Google database were searched manually for grey literature. Two reviewers independently assessed study eligibility, risk of bias and extracted the data. We performed a descriptive presentation of the performance of E6/E7 mRNA test (in terms of sensitivity, specificity, negative and positive predictive values) for the detection of CIN2 + .
RESULTS
Out of 231 applicable citations, we have included 29 articles that included a total of 23,576 study participants (age range, 15-84 years) who had different cervical pathologies. Among the participants who had cervical histology, the proportion of CIN2+ was between 10.6 and 90.6%. Using histology as a gold standard, 11 studies evaluated the PreTect HPV Proofer, 7 studies evaluated the APTIMA HPV assay (Gen-Probe) and 6 studies evaluated the Quantivirus® HPV assay. The diagnostic performance of these three most common mRNA testing tools to detect CIN2+ was; 1) PreTect Proofer; median sensitivity 83%, specificity 73%, PPV 70 and NPV 88.9%. 2) APTIMA assay; median sensitivity 91.4%, specificity 46.2%, PPV 34.3% and NPV 96.3%. 3) Quantivirus®: median sensitivity 86.1%, specificity 54.6%, PPV 54.3% and NPV was at 89.3%. Further, the area under the receiver operating characteristics (AU-ROC) curve varied between 63.8 and 90.9%.
CONCLUSIONS
The reported diagnostic accuracy implies that HPV mRNA based tests possess diagnostic relevance to detect CIN2+ and could potentially be considered in areas where there is no histology facility. Further studies including its cost should be considered.
PubMed: 32047531
DOI: 10.1186/s13027-020-0278-x -
International Journal of Clinical... Oct 2022Fluorescence in situ hybridization (FISH) is a technique that uses fluorescently labeled DNA probes. Many studies have evaluated the ROC curve (sensitivity and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Fluorescence in situ hybridization (FISH) is a technique that uses fluorescently labeled DNA probes. Many studies have evaluated the ROC curve (sensitivity and specificity) with the FISH method to diagnose upper tract urothelial carcinoma (UTUC). The current meta-analysis was performed to examine the diagnostic power of the FISH method in UTUC.
METHODS
We reviewed databases and methodically obtained papers for analysis until April 25th, 2022. The Meta-disc V.1.4 and Comprehensive Meta-Analysis V.3.3 software calculated the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, area under the curve (AUC), and summary receiver-operating characteristic (SROC). The I and Chi-square tests were used to examine the heterogeneity. Finally, the publication bias was estimated using Begg's and Egger's tests.
RESULTS
A total of 13 articles included 1,067 participants (439 cases and 628 controls). The overall pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.72 (95% CI 0.67-0.76), 0.95 (95% CI 0.93-0.97), 10.42 (95% CI 5.84-18.60), 0.29 (95% CI 0.21-0.40), 38.55 (95% CI 18.58-79.96), and 0.91, respectively. No publication bias was reported based on Begg's and Egger's tests (Begg's p = 0.200; Egger's p = 0.151).
CONCLUSION
This paper clearly shows that the high specificity and acceptable sensitivity of the FISH method make it a promising diagnostic method for UTUC in urine samples. However, further research with higher statistical numbers is needed to strengthen the correlation and be used for diagnostic applications.
Topics: Area Under Curve; Carcinoma, Transitional Cell; Humans; In Situ Hybridization, Fluorescence; ROC Curve; Sensitivity and Specificity; Urinary Bladder Neoplasms
PubMed: 35856125
DOI: 10.1007/s10147-022-02216-7 -
The Cochrane Database of Systematic... Mar 2022Complete deletion of both the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q), known as 1p/19q codeletion, is a mutation that can occur in... (Review)
Review
BACKGROUND
Complete deletion of both the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q), known as 1p/19q codeletion, is a mutation that can occur in gliomas. It occurs in a type of glioma known as oligodendroglioma and its higher grade counterpart known as anaplastic oligodendroglioma. Detection of 1p/19q codeletion in gliomas is important because, together with another mutation in an enzyme known as isocitrate dehydrogenase, it is needed to make the diagnosis of an oligodendroglioma. Presence of 1p/19q codeletion also informs patient prognosis and prediction of the best drug treatment. The main two tests in use are fluorescent in situ hybridisation (FISH) and polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) assays (also known as PCR-based short tandem repeat or microsatellite analysis). Many other tests are available. None of the tests is perfect, although PCR-based LOH is expected to have very high sensitivity.
OBJECTIVES
To estimate the sensitivity and specificity and cost-effectiveness of different deoxyribonucleic acid (DNA)-based techniques for determining 1p/19q codeletion status in glioma.
SEARCH METHODS
We searched MEDLINE, Embase and BIOSIS up to July 2019. There were no restrictions based on language or date of publication. We sought economic evaluation studies from the results of this search and using the National Health Service Economic Evaluation Database.
SELECTION CRITERIA
We included cross-sectional studies in adults with glioma or any subtype of glioma, presenting raw data or cross-tabulations of two or more DNA-based tests for 1p/19q codeletion. We also sought economic evaluations of these tests.
DATA COLLECTION AND ANALYSIS
We followed procedures outlined in the Cochrane Handbook for Diagnostic Test Accuracy Reviews. Two review authors independently screened titles/abstracts/full texts, performed data extraction, and undertook applicability and risk of bias assessments using QUADAS-2. Meta-analyses used the hierarchical summary ROC model to estimate and compare test accuracy. We used FISH and PCR-based LOH as alternate reference standards to examine how tests compared with those in common use, and conducted a latent class analysis comparing FISH and PCR-based LOH. We constructed an economic model to evaluate cost-effectiveness.
MAIN RESULTS
We included 53 studies examining: PCR-based LOH, FISH, single nucleotide polymorphism (SNP) array, next-generation sequencing (NGS), comparative genomic hybridisation (CGH), array comparative genomic hybridisation (aCGH), multiplex-ligation-dependent probe amplification (MLPA), real-time PCR, chromogenic in situ hybridisation (CISH), mass spectrometry (MS), restriction fragment length polymorphism (RFLP) analysis, G-banding, methylation array and NanoString. Risk of bias was low for only one study; most gave us concerns about how patients were selected or about missing data. We had applicability concerns about many of the studies because only patients with specific subtypes of glioma were included. 1520 participants contributed to analyses using FISH as the reference, 1304 participants to analyses involving PCR-based LOH as the reference and 262 participants to analyses of comparisons between methods from studies not including FISH or PCR-based LOH. Most evidence was available for comparison of FISH with PCR-based LOH (15 studies, 915 participants): PCR-based LOH detected 94% of FISH-determined codeletions (95% credible interval (CrI) 83% to 98%) and FISH detected 91% of codeletions determined by PCR-based LOH (CrI 78% to 97%). Of tumours determined not to have a deletion by FISH, 94% (CrI 87% to 98%) had a deletion detected by PCR-based LOH, and of those determined not to have a deletion by PCR-based LOH, 96% (CrI 90% to 99%) had a deletion detected by FISH. The latent class analysis suggested that PCR-based LOH may be slightly more accurate than FISH. Most other techniques appeared to have high sensitivity (i.e. produced few false-negative results) for detection of 1p/19q codeletion when either FISH or PCR-based LOH was considered as the reference standard, although there was limited evidence. There was some indication of differences in specificity (false-positive rate) with some techniques. Both NGS and SNP array had high specificity when considered against FISH as the reference standard (NGS: 6 studies, 243 participants; SNP: 6 studies, 111 participants), although we rated certainty in the evidence as low or very low. NGS and SNP array also had high specificity when PCR-based LOH was considered the reference standard, although with much more uncertainty as these results were based on fewer studies (just one study with 49 participants for NGS and two studies with 33 participants for SNP array). G-banding had low sensitivity and specificity when PCR-based LOH was the reference standard. Although MS had very high sensitivity and specificity when both FISH and PCR-based LOH were considered the reference standard, these results were based on only one study with a small number of participants. Real-time PCR also showed high specificity with FISH as a reference standard, although there were only two studies including 40 participants. We found no relevant economic evaluations. Our economic model using FISH as the reference standard suggested that the resource-optimising test depends on which measure of diagnostic accuracy is most important. With FISH as the reference standard, MLPA is likely to be cost-effective if society was willing to pay GBP 1000 or less for a true positive detected. However, as the value placed on a true positive increased, CISH was most cost-effective. Findings differed when the outcome measure changed to either true negative detected or correct diagnosis. When PCR-based LOH was used as the reference standard, MLPA was likely to be cost-effective for all measures of diagnostic accuracy at lower threshold values for willingness to pay. However, as the threshold values increased, none of the tests were clearly more likely to be considered cost-effective.
AUTHORS' CONCLUSIONS
In our review, most techniques (except G-banding) appeared to have good sensitivity (few false negatives) for detection of 1p/19q codeletions in glioma against both FISH and PCR-based LOH as a reference standard. However, we judged the certainty of the evidence low or very low for all the tests. There are possible differences in specificity, with both NGS and SNP array having high specificity (fewer false positives) for 1p/19q codeletion when considered against FISH as the reference standard. The economic analysis should be interpreted with caution due to the small number of studies.
Topics: Brain Neoplasms; Chromosomes, Human, Pair 1; Cost-Benefit Analysis; Cross-Sectional Studies; DNA; Diagnostic Tests, Routine; Glioma; Humans; Oligodendroglioma; State Medicine
PubMed: 35233774
DOI: 10.1002/14651858.CD013387.pub2 -
Frontiers in Aging Neuroscience 2021Alzheimer's disease (AD) is characterized by specific alterations of brain DNA methylation (DNAm) patterns. Age and sex, two major risk factors for AD, are also known to...
Alzheimer's disease (AD) is characterized by specific alterations of brain DNA methylation (DNAm) patterns. Age and sex, two major risk factors for AD, are also known to largely affect the epigenetic profiles in brain, but their contribution to AD-associated DNAm changes has been poorly investigated. In this study we considered publicly available DNAm datasets of four brain regions (temporal, frontal, entorhinal cortex, and cerebellum) from healthy adult subjects and AD patients, and performed a meta-analysis to identify sex-, age-, and AD-associated epigenetic profiles. In one of these datasets it was also possible to distinguish 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) profiles. We showed that DNAm differences between males and females tend to be shared between the four brain regions, while aging differently affects cortical regions compared to cerebellum. We found that the proportion of sex-dependent probes whose methylation is modified also during aging is higher than expected, but that differences between males and females tend to be maintained, with only a few probes showing age-by-sex interaction. We did not find significant overlaps between AD- and sex-associated probes, nor disease-by-sex interaction effects. On the contrary, we found that AD-related epigenetic modifications are significantly enriched in probes whose DNAm varies with age and that there is a high concordance between the direction of changes (hyper or hypo-methylation) in aging and AD, supporting accelerated epigenetic aging in the disease. In summary, our results suggest that age-associated DNAm patterns concur to the epigenetic deregulation observed in AD, providing new insights on how advanced age enables neurodegeneration.
PubMed: 33790779
DOI: 10.3389/fnagi.2021.639428 -
Experimental Parasitology Dec 2019Studies of the primers that were designed to detect New World Leishmania were systematically reviewed to report the characteristics of each target, detection limit,...
Studies of the primers that were designed to detect New World Leishmania were systematically reviewed to report the characteristics of each target, detection limit, specificity of the primers designed and diagnostic sensibility. The papers identified in the databases PubMed and Web of Science involved 50 studies. Minicircle is the most applied target in molecular research for diagnosis, due to its high sensitivity in detecting Leishmania in different clinical samples, a characteristic that can be partially attributed to the higher number of copies of the minicircle per cell. The other molecular targets shown in this review were less sensitive to diagnostic use because of the lower number of copies of the target gene per cell, but more specific for identification of the subgenus and/or species. The choice of the best target is an important step towards the result of the research. The target allows the design of primers that are specific to the genus, subgenus or a particular species and also imparts sensitivity to the method for diagnosis. The findings of this systematic review provide the advantages and disadvantages of the main molecular targets and primers designed for New World Leishmania, offering information so that the researcher can choose the PCR system best suited to their research need. This is a timely and extremely thorough review of the primers designed for New World Leishmania.
Topics: DNA Primers; DNA, Protozoan; Humans; Leishmania; Leishmaniasis, Cutaneous; Limit of Detection; Polymerase Chain Reaction; Sensitivity and Specificity
PubMed: 31605671
DOI: 10.1016/j.exppara.2019.107773