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EClinicalMedicine Aug 2023Anal cancer prevention has two critical points: the incidence rate is several fold higher for some groups, such as people living with human immunodeficiency virus (HIV)...
BACKGROUND
Anal cancer prevention has two critical points: the incidence rate is several fold higher for some groups, such as people living with human immunodeficiency virus (HIV) and men who have sex with men (MSM), and there is not a well-defined guideline for its screening. This systematic review evaluates the accuracy of DNA HRHPV (high-risk human papillomavirus), mRNA HPV, DNA HPV16 isolated and p16 staining biomarkers in anal canal smears for identifying anal intraepithelial neoplasia (AIN) 2 or 3, summarised as anal high-grade squamous intraepithelial lesions (aHSIL), and cancer.
METHODS
We searched the MEDLINE, Cochrane Library and Embase electronic databases as well as Grey literature to identify eligible papers published up to 31st July 2022. This systematic review and meta-analysis included observational studies comparing biomarker tests to histopathology after HRA (High-resolution Anoscopy) as a reference standard. We (ACM, TF) analysed studies in which patients of both sexes were screened for anal cancer using DNA HRHPV, mRNA HPV, DNA HPV16 and/or p16 biomarkers. The analysis was performed in pairs, for instance AIN2 or worse (AIN2+) vs. AIN1, HPV infection and normal (AIN1-). PROSPERO CRD42015024201.
FINDINGS
We included 21 studies with 7445 patients. DNA HR HPV showed a higher sensitivity 92.4% (95% CI 84.2-96.5), specificity 41.7% (95% CI 33.9-44.9) and AUC 0.67, followed by the mRNA HPV test, with a sensitivity 77.3% (95% CI 73.2%-80.9%), specificity 61.9% (95% CI 56.6-66.9) and AUC 0.78. DNA HPV16 showed higher specificity 71.7% (95% CI 55.3-83.8), followed by p16 test, 64.1% (95% CI 51.0-75.4); Sensitivity of DNA HPV16 was 53.3% (95% CI 35.4-70.3) and AUC 0.69, while p16 had a sensitivity of 68.8% (95% CI 47.9-84.1) and AUC 0.74. Subgroup analysis of MSM with HIV, with 13 studies and 5123 patients, showed similar accuracy, with a bit higher sensitivities and lower specificities. Considering the measure of the total between-study variability, mRNA HPV tests showed the smallest area of the 95% prediction ellipse, 6.0%, influenced by the low logit sensitivity, 0.011. All other groups of tests exceed 50% prediction ellipse area, which represent a high heterogeneity.
INTERPRETATION
Our findings suggested that DNA HR HPV can be a useful tool for screening for aHSIL and anal cancer if followed by biomarker with a higher specificity. As an isolated test, mRNA HPV had better performance.
FUNDING
There was no funding source for this study.
PubMed: 37588624
DOI: 10.1016/j.eclinm.2023.102128 -
Journal of Oncology 2019This systematic review evaluates the accuracy of the mRNA HPV biomarker in cervical smears to identify cervical intraepithelial neoplasia (CIN) 2 or 3 and cervical... (Review)
Review
OBJECTIVE
This systematic review evaluates the accuracy of the mRNA HPV biomarker in cervical smears to identify cervical intraepithelial neoplasia (CIN) 2 or 3 and cervical cancer.
DATA SOURCE
Eligible studies were identified by performing a search of electronic databases on Medline via Pubmed, Lilacs, Cochrane Library, Embase, and Grey literature for papers published between January 1990 and June 2018.
STUDY ELIGIBILITY CRITERIA
As no randomized studies were identified, this review focuses on observational studies in which the mRNA HPV diagnostic test was compared to a histopathology reference standard. We analyzed studies that included women screened for cervical cancer using mRNA HPV.
STUDY APPRAISAL AND SYNTHESIS METHODS
After screening, 61 studies including 29,674 patients met the inclusion criteria and were analyzed. Dichotomization was performed by defining CIN2 or worse (CIN2+) versus CIN1, HPV infection, and normal (CIN 1-). The analysis was discriminated by the following tests: Aptima, PreTect HPV Profeer, NucliSens EasyQ HPV, OncoTect, and Quantivirus.
RESULTS
Analyzing by technique, Aptima, with 28 studies, exhibited superior performance, showing for the outcomes CIN2+ and CIN3+ an AUC of 0.88 (0.82-0.95) and 0.91 (0.84-0.99), a pooled sensitivity of 92.8% (95%CI 91.9-93.7) and 95.6% (95%CI 94.5-96.5), and a pooled specificity of 60.5% (95%CI 59.8-61.3) and 61.9% (95%CI 61.1-62.7), respectively.
CONCLUSION
This study supports the current hypothesis that the mRNA HPV assay is an adequate tool for secondary cervical cancer screening.
PubMed: 31281360
DOI: 10.1155/2019/6935030 -
Danish Medical Journal Mar 2016The study of potential biomarkers in haematological malignancies has gained momentum in past decades. We compiled a systematic review to outline potential biomarkers... (Review)
Review
INTRODUCTION
The study of potential biomarkers in haematological malignancies has gained momentum in past decades. We compiled a systematic review to outline potential biomarkers based on alternative pre-mRNA splicing that were suggested to be clinically useful for the diagnosis, prognosis and response to therapeutics in diffuse large B-cell lymphoma (DLBCL).
METHODS
A comprehensive search of the literature in PubMed, Embase and Scopus was performed and supplemented with screening of reference lists. Only articles concerning potential biomarkers originating from reports on alternative pre-mRNA splicing were included. The contributions of these studies will help develop personalised medicine. Therefore, the clinical utility of the potential biomarkers was evaluated.
RESULTS
A total of 16 studies were included of which eight described seven different potential diagnostic biomarkers. Eight studies reported two potential prognostic biomarkers for CD44, its spliced mRNA variants and the resulting proteins that were the most frequently reported. Furthermore, two studies reported two proteins originating from alternative pre-mRNA splicing as potentially predictive biomarkers.
CONCLUSIONS
Alternative pre-mRNA splicing is a promising potential diagnostic, prognostic and predictive biomarker for the identification of pathogenic impacts in DLBCL. The use of these potential biomarkers in the clinical management of DLBCL awaits prospective clinical validation supporting its potential to contribute to the shift towards more personalised medicine.
Topics: Biomarkers, Tumor; Disease Management; Humans; Lymphoma, Large B-Cell, Diffuse; Prognosis; RNA Precursors
PubMed: 26931194
DOI: No ID Found -
Blood Cancer Journal Jun 2020B-cell maturation antigen (BCMA) plays a critical role in regulating B-cell proliferation and survival. There is evidence for BCMA expression in various hematologic... (Meta-Analysis)
Meta-Analysis
B-cell maturation antigen (BCMA) plays a critical role in regulating B-cell proliferation and survival. There is evidence for BCMA expression in various hematologic malignancies, suggesting that BCMA may play an important role as a biomarker or therapeutic target in these diseases. Given advances in understanding the role of BCMA in B-cell development and the promise of BCMA as a therapeutic target, a systematic review is needed to rigorously assess the evidence for BCMA expression and identify areas of consensus and future research. The objective of this review was to summarize the evidence on BCMA protein and mRNA expression across hematologic malignancies. Using a PubMed database search up to 28 August 2019, a systematic literature review of publications reporting BCMA expression in patients with hematologic malignancies was conducted. Data from published congress abstracts presented at the American Society of Clinical Oncology and the American Society of Hematology were also searched. Studies that assessed BCMA expression (protein or mRNA) in patients of any age with hematologic malignancies were included. A total of 21 studies met inclusion criteria and were included in the review. BCMA was expressed in several hematologic malignancies, including multiple myeloma (MM), chronic lymphocytic leukemia, acute B-lymphoblastic leukemia, non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma. BCMA was expressed at uniformly high levels across all 13 MM studies and at low to moderate levels in acute myeloid leukemia and acute lymphoblastic leukemia. These results suggest that BCMA is a relevant target in MM as well as in a subset of B-cell leukemia. BCMA expression in Hodgkin lymphoma and NHL varied across studies, and further research is needed to determine the utility of BCMA as an antibody target and biomarker in these diseases. Differences in sample type, timing of sample collection, and laboratory technique used may have affected the reporting of BCMA levels.
Topics: B-Cell Maturation Antigen; Gene Expression Regulation, Neoplastic; Hematologic Neoplasms; Hodgkin Disease; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Multiple Myeloma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; RNA, Messenger
PubMed: 32606424
DOI: 10.1038/s41408-020-0337-y -
Clinical and Translational... Jun 2016Despite moderate to high detection rates of fecal immunochemical tests (FITs) of colorectal cancer (CRC), detection of adenomas remains limited. Further stool tests... (Review)
Review
OBJECTIVES
Despite moderate to high detection rates of fecal immunochemical tests (FITs) of colorectal cancer (CRC), detection of adenomas remains limited. Further stool tests exist, which are not used in routine practice, such as DNA or RNA markers and protein markers. We aimed at systematically investigating and summarizing evidence for diagnostic performance of combinations of FIT with other stool tests compared with FIT alone in early detection of CRC and its precursors.
METHODS
We systematically reviewed studies that evaluated FITs in combination with other stool tests and compared measures of diagnostic accuracy with and without additional stool tests. PubMed and Web of Science were searched from inception to May 2015. Reference lists of eligible studies were also screened. Two reviewers extracted data independently.
RESULTS
Some of the reports on DNA, RNA, or tissue tests, including tests based on DNA mutations, methylation, and integrity in selected genes as well as microRNA expression, showed some improvements of diagnostic test accuracy. In contrast, so far assessed stool protein markers did generally not lead to substantial improvements in performance of FIT when added to the latter. Many marker combinations were reported only in one study each, and few studies were conducted in a true screening setting.
CONCLUSIONS
Several stool markers show potential to improve performance of FITs. However, the results require confirmation in further studies, which should also evaluate the costs and cost-effectiveness of combined screening strategies.
PubMed: 27253514
DOI: 10.1038/ctg.2016.29 -
Open Forum Infectious Diseases May 2019The incidence of high-risk human papillomavirus (HR-HPV)-induced anal cancer is increasingly problematic among HIV-positive patients. Anal cancer is preceded by...
BACKGROUND
The incidence of high-risk human papillomavirus (HR-HPV)-induced anal cancer is increasingly problematic among HIV-positive patients. Anal cancer is preceded by precursor lesions, anal intraepithelial neoplasia (AIN). AIN detection requires high-resolution anoscopy, a cumbersome and time-consuming procedure. We aggregated evidence on anal swab-based tests to detect AIN in HIV-positive patients.
METHODS
We searched MEDLINE and EMBASE for cross-sectional studies on AIN detection with anal cytology, HR-HPV DNA detection, HPV E6/E7 mRNA analysis, and P16INK4a and Ki-67 immunostaining. Summary estimates of sensitivity and specificity were calculated using bivariate logistic regression. Cytology was reported using the terms squamous intra-epithelial lesion (SIL) for AIN and high-grade SIL (HSIL) for high-grade AIN (HGAIN).
RESULTS
We included 22 studies. Using cytology with a cutoff of any SIL to detect HGAIN, we detected a sensitivity of 82% (95% CI, 74%-87%) and specificity of 45% (95% CI, 44%-66%); with the cutoff of HSIL, the sensitivity was 44% (95% CI, 45%-67%) and the specificity was 79% (95% CI, 69%-87%). The sensitivity of HPV DNA to detect HGAIN was 91% (95% CI, 82%-95%) and the specificity was 27% (95% CI, 21%-33%). For MSM, the positive predictive value (PPV) of cytology with a cutoff of any SIL was 36% (95% CI, 23%-50%) and the negative predictive value (NPV) was 87% (95% CI, 78%-93%), whereas cytology with a cutoff of HSIL had a PPV of 62% (95% CI, 50%-73%) and an NPV of 78% (95% CI, 65%-87%). The PPV of HR-HPV DNA detection was 37% (95% CI, 20%-57%) and the NPV was 87% (95% CI, 79%-93%).
CONCLUSIONS
Given its sensitivity, cytology with a cutoff of any SIL could be considered as a triaging method, whereas cytology with a cutoff of HSIL had better specificity and could be used for quality assurance. HR-HPV DNA detection had poor specificity and PPV, making it unsuitable for triage.
PubMed: 31123696
DOI: 10.1093/ofid/ofz191