Publications
60 results found
Bowden SJ, Ellis L, Kalliala I, et al., 2023, Protocol for a systematic review and meta-analysis of the diagnostic test accuracy of host and HPV DNA methylation in cervical cancer screening and management, BMJ Open, ISSN: 2044-6055
Kechagias KS, Zafeiri M, Triantafyllidis KK, et al., 2023, Primary Melanoma of the Cervix Uteri: A Systematic Review and Meta-Analysis of the Reported Cases, BIOLOGY-BASEL, Vol: 12
Giannos P, Kechagias K, Paraskevaidi M, et al., 2023, Female dynamics in authorship of scientific publications in the Public Library of Science: a 10-year bibliometric analysis of biomedical research, European Journal of Investigation in Health, Psychology and Education, Vol: 13, Pages: 228-237, ISSN: 2254-9625
Women are generally underrepresented in science, technology, engineering, and mathematics (STEM). As scientific production reflects scholarly impact and participation in the scientific process, the number of journal publications forms a pertinent measure of academic productivity. This study examined the prevalence and evolution of female representation in prominent author positions across multidisciplinary biomedical research. Publications from seven exemplar cross-specialty journals of the Public Library of Science (PLoS Medicine, PLoS Biology, PLoS One, PLoS Computational Biology, PLoS Genetics, PLoS Pathogens, and PLoS Neglected Tropical Diseases) between January 2010 and December 2020 were extracted from Web of Science. Using Genderize.io, the gender of authors from their first names was estimated using a 75% threshold. The association between female prevalence in first and last authorship and journal was evaluated using a binary logistic regression, and odds ratios were estimated against a 50:50 reference on gender. In 266,739 publications, 43.3% of first authors and 26.7% of last authors were females. Across the ten-year period, female first authorship increased by 19.6% and last authorship by 3.2%. Among all journals, PLoS Neglected Tropical Diseases had the greatest total proportion of female first authors (45.7%) and PLoS Medicine of female last authors (32%), while PLoS Computational Biology had the lowest proportion in these categories (23.7% and 17.2%). First authors were less likely to be females in all PLoS journals (p < 0.05) except for PLoS Neglected Tropical Diseases (odds ratio: 0.84, 95% confidence interval: 0.71–1.00), where the odds of female authorship were not significantly different (p = 0.054). Last authors were not more likely to be females in all PLoS journals (p < 0.001). Overall, women still appear underrepresented as first authors in biomedical publications and their representation as last authors has severely lagged. Effort
dos Santos RF, Paraskevaidi M, Lima KMG, 2023, A review of biospectroscopy coupled with chemometrics for Alzheimer's disease diagnosis, APPLIED SPECTROSCOPY REVIEWS, ISSN: 0570-4928
Kechagias K, Katsikas-Triantafyllidis K, Geropoulos G, et al., 2022, Diverticulitis during pregnancy: a systematic review of the reported cases, Frontiers in Medicine, Vol: 9, ISSN: 2296-858X
Background: Diverticular disease of the colon represents a common clinical condition in the western world. Its prevalence increases with age and only 5% of cases occur in adults younger than 40 years of age, making it a rare condition during pregnancy. The aim of this review was to provide an overview of the reported cases of diverticulitis during pregnancy.Methods: We conducted a systematic review of the literature based on preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. We searched three different electronic databases namely PubMed, Scopus and Web of Science from inception to December 2021. Literature search and data extraction were completed in duplicates.Results: The initial search yielded 564 articles from which 12 were finally included in our review. Ten articles were case reports and two were observational studies. The mean age of the cases was 34 years. The presenting complain was provided for 11 cases. The majority of the patients (10/11, 91%) presented with abdominal pain located mainly on the left (6/11, 55%) or right (4/11, 36%) iliac fossa. The most common diagnostic modality used for the diagnosis of the condition was ultrasonography in nine cases (9/12, 75%) followed by magnetic resonance imaging (MRI) in two cases (2/12, 17%). In spite of clinical and radiological evaluation, the initial diagnosis was inaccurate in seven cases (7/12, 58%). The therapeutic approach was available for 11 cases and it was based on the administration of intravenous antibiotics in six cases (6/11, 55%) and surgical management in five cases (5/11, 45%). Data for the type of delivery was provided in nine studies with five patients (5/9, 56%) delivering vaginally and four patients (4/9, 44%) delivering with cesarean section.Conclusion: As advanced maternal age becomes more common, the frequency of diverticulitis in pregnancy may increase. Although available guidelines do not exist, the clinical awareness, early recognition of the disorde
Ramirez CAM, Stringfellow H, Naik R, et al., 2022, Infrared Spectroscopy of Urine for the Non-Invasive Detection of Endometrial Cancer, CANCERS, Vol: 14
Dos Santos RF, Paraskevaidi M, Mann DMA, et al., 2022, Alzheimer's disease diagnosis by blood plasma molecular fluorescence spectroscopy (EEM), Scientific Reports, Vol: 12, ISSN: 2045-2322
Despite tremendous research advances in detecting Alzheimer's disease (AD), traditional diagnostic tests remain expensive, time-consuming or invasive. The search for a low-cost, rapid, and minimally invasive test has marked a new era of research and technological developments toward establishing blood-based AD biomarkers. The current study has employed excitation-emission matrices (EEM) of fluorescence spectroscopy combined with machine learning to diagnose AD using blood plasma samples from 230 individuals (83 AD patients from 147 healthy controls). To evaluate the performance of the classification algorithms, we calculated the commonly used figures of merit (accuracy, sensitivity and specificity) and figures of merit that take into account the samples unbalance and the discrimination power of the models, as F2-score (F2), Matthews correlation coefficient (MCC) and test effectiveness ([Formula: see text]). The classification models achieved satisfactory results: Parallel Factor Analysis with Quadratic Discriminant Analysis (PARAFAC-QDA) with 83.33% sensitivity, 100% specificity, 86.21% F2; and Tucker3-QDA with 91.67% sensitivity, 95.45% specificity and 91.67% F2. In addition, the classifiers show high overall performance with 94.12% accuracy and 0.87 MCC. Regarding the discrimination power between healthy and AD patients, the classification algorithms showed high effectiveness with the mean scores separated by three or more standard deviations. The PARAFAC's spectral profiles and the wavelength values from both models loading profiles can be used in future research to relate this information to plasma AD biomarkers. Our results point to a rapid, low-cost and minimally invasive blood-based method for AD diagnosis.
Kechagias K, Kalliala I, Bowden S, et al., 2022, The role of HPV vaccination on HPV infection and recurrence of HPV-related disease after local surgical treatment: a systematic review and meta-analysis., The BMJ, Vol: 378, ISSN: 0959-8138
Objective: The efficacy of prophylactic human papillomavirus (HPV) vaccines after surgical treatment for pre-invasive genital disease remains unclear. Our aim was to explore the efficacy of HPV vaccination on HPV infection risk and risk of recurrent HPV-related disease in individuals undergoing local surgical treatment for cervical or other HPV-related disease.Methods: Design: Systematic review and meta-analysisData sources: PubMed/Medline, Scopus, Cochrane, Web of Science and ClinicalTrials.gov were screened from inception until March 2021.Inclusion criteria: Studies reporting on HPV infection risk and recurrence of HPV-related disease after local surgical treatment of pre-invasive genital disease in vaccinated individuals. Outcome measures: Primary: Recurrence risk for cervical intraepithelial neoplasia grade 2 or higher (CIN2+)(follow-up as reported by individual studies); Secondary: risk of HPV infection, other HPV-related lesions.Data extraction and risk of bias assessment: Independent and in duplicate data extraction and quality assessment using ROBINS-I and RoB-2 tools was performed for observational studies and randomised controlled trials (RCTs). Grading of Recommendations Assessment, Development and Evaluation (GRADE) was implemented for the primary outcome.Data synthesis: Observational studies and RCTs were analysed separately from post-hoc analyses of RCTs. Pooled risk ratios (RR) and 95% confidence intervals (95% CI) were calculated using a random-effects (RE) meta-analysis model. The restricted maximum likelihood was used as an estimator for heterogeneity, and the Hartung-Knapp-Sidik-Jonkman method was used to derive confidence intervals.Results: Twenty-two articles met the inclusion criteria of the review; eighteen studies also reported data from a non-vaccinated group and were included in the meta-analyses (12 observational; 2 RCTs and 4 post-hoc analyses of RCTs). The risk of CIN2+ recurrence was reduced in vaccinated when compared to non-vaccinated
Athanasiou A, Veroniki AA, Efthimiou O, et al., 2022, Comparative effectiveness and reproductive morbidity of local treatments for cervical intraepithelial neoplasia and stage 1a1 cervical cancer: a systematic review and network meta-analysis, The Lancet Oncology, Vol: 23, ISSN: 1213-9432
Background: In this network meta-analysis, we compared the effectiveness and reproductive morbidity associated with various treatment methods for cervical intraepithelial neoplasia (CIN).Methods: We searched electronic databases (MEDLINE, Embase, CENTRAL) from inception until 9 March 2022 for randomised and non-randomised studies reporting on oncological and reproductive outcomes after excisional or ablative CIN treatments. The primary outcomes were any treatment failure (defined as any abnormal histology or cytology) and preterm birth (<37 weeks). The network for prematurity included also women with untreated CIN (colposcopy group). We extracted study-level data and conducted random-effects network meta-analyses to obtain odds ratios (ORs) with 95% confidence intervals. Within- and across-study risk of bias was assessed using Cochrane tools. PROSPERO registration: CRD42018115495 and CRD42018115508.Findings: Searches retrieved 11,987 citations. The networks for treatment failure and prematurity included 19,240 and 68,817 participants across 71 (25 randomised) and 29 (two randomised) studies, respectively. Compared to large loop excision of the transformation zone (LLETZ), risk of treatment failure was lower for other excisional (laser conisation: OR=0·59, 0·44–0·79; cold knife conisation [CKC]: OR=0·63, 0·50–0·81) and higher for ablative techniques (laser ablation: OR=1·69, 1·27–2·24; cryotherapy: OR=1·84, 1·33–2·55). Compared to colposcopy group, risk of prematurity was higher for all excisional techniques (CKC: OR=2·27, 1·70–3·02; laser conisation: OR=1·77, 1·29–2·43; LLETZ: OR=1·37, 1·16–1·62), whilst estimates were uncertain for ablative methods.Interpretation: More radical excisional techniques reduce the risk of treatment failure but increase the risk of subsequent preter
Zikopoulos A, Galani A, Siristatidis C, et al., 2022, Is Hysteroscopy Prior to IVF Associated with an Increased Probability of Live Births in Patients with Normal Transvaginal Scan Findings after Their First Failed IVF Trial?, JOURNAL OF CLINICAL MEDICINE, Vol: 11
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Mitra A, MacIntyre DA, Paraskevaidi M, et al., 2021, The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia, Genome Medicine: medicine in the post-genomic era, Vol: 13, ISSN: 1756-994X
Background:Vaginal microbiota (VMB) composition is altered in women with cervical intra-epithelial neoplasia (CIN) compared to healthy controls and is associated with disease progression. However, the impact of CIN excision on the VMB and innate immunity is not known. This observational study aims to explore the impact of CIN excision on the VMB, antimicrobial peptides (AMP) and proinflammatory cytokines.Methods:We sampled 103 non-pregnant, premenopausal women at the time of excisional treatment for CIN and at their 6-month follow-up visit. A further 39 untreated controls with normal cytology were also sampled. We used metataxonomics to group vaginal swab samples into community state types (CSTs) and ELISA to quantify cytokine and AMP levels in matched vaginal secretions. Analyses were performed to compare the bacterial composition and immune analyte levels before and after CIN excision and in healthy controls.Results:Women with CIN had significantly higher rates of Lactobacillus species depletion pre-treatment compared to healthy controls (CST IV 21/103, 20% vs 1/39, 3%, p = 0.0081). Excision did not change the VMB composition, with CST IV remaining significantly more prevalent after excision compared to untreated, healthy controls (CST IV 19/103, 20% vs 1/39, 3%, p = 0.0142). Prevotella bivia and Sneathia amnii were significantly higher in samples before treatment compared to untreated controls, and Prevotella bivia remained significantly higher amongst the treated, with less Lactobacillus crispatus compared to untreated controls. IL-1β and IL-8 remained significantly elevated pre- (p < 0.0001 and p = 0.0014, respectively) and post-treatment (p < 0.0001 and p = 0.0035, respectively) compared to untreated controls. Levels of human beta-defensin-1 and secretory leukocyte protease inhibitor were both significantly reduced following CIN excision (p < 0.0001); however, their levels remained lower than controls post-treatment.Conclusions:Women with CIN hav
Giannos P, Kechagias K, Bowden S, et al., 2021, PCNA in cervical intraepithelial neoplasia and cervical cancer: an interaction network analysis of differentially expressed genes, Frontiers in Oncology, Vol: 11, Pages: 1-8, ISSN: 2234-943X
The investigation of differentially expressed genes (DEGs) and their interactome could provide valuable insights for thedevelopment of markers to optimise cervical intraepithelial neoplasia (CIN) screening and treatment. This study investigatedpatients with cervical disease to identify gene markers whose dysregulated expression and protein interaction interface werelinked with CIN and cervical cancer (CC). Literature search of microarray datasets containing cervical epithelial samples wasconducted in Gene Expression Omnibus and Pubmed/Medline from inception untill March 2021. Retrieved DEGs were used toconstruct two protein-protein interaction (PPI) networks. Module DEGs that overlapped between CIN and CC samples, were rankedbased on 11 topological algorithms. The highest-ranked hub gene was retrieved and its correlation with prognosis, tissueexpression and tumour purity in patients with CC, was evaluated. Screening of the literature yielded 12 microarray datasets(GSE7803, GSE27678, GSE63514, GSE6791, GSE7803, GSE9750, GSE27678, GSE29570, GSE39001, GSE63514, GSE63678, GSE67522). TwoPPI networks from CIN and CC samples were constructed and consisted of 1704 and 3748 DEGs along 21393 and 79828 interactions,respectively. Two gene clusters were retreived in the CIN network and three in the CC network. Multi-algorithmic topologicalanalysis revealed PCNA as the highest ranked hub gene between the two networks, both in terms of expression and interactions.Further analysis revealed that while PCNA was overexpressed in CC tissues, it was correlated with favourable prognosis (log-rank P=0.022, HR=0.58) and tumour purity (P=9.86 × 10-4, partial rho=0.197) in CC patients. This study identified that cervical PCNAexhibited multi-algorithmic topological significance among DEGs from CIN and CC samples. Overall, PCNA may serve as a potentialgene marker of CIN progression. Experimental validation is necessary to examine its value in patients with cervical disease.
Bauer-Negrini G, Deckmann I, Schwingel GB, et al., 2021, The role of T-cells in neurobehavioural development: Insights from the immunodeficient nude mice, BEHAVIOURAL BRAIN RESEARCH, Vol: 418, ISSN: 0166-4328
Bowden S, Bodinier B, Paraskevaidi M, et al., 2021, 200 Can methylation signals of cervical cancer enhance cervical screening?: an epigenome-wide association study on the Illumina 850k array, ESGO 2021 Congress, Publisher: BMJ Publishing Group, Pages: A12-A17, ISSN: 1048-891X
Paraskevaidi M, Matthew BJ, Holly BJ, et al., 2021, Clinical applications of infrared and Raman spectroscopy in the fields of cancer and infectious diseases, Applied Spectroscopy Reviews, Vol: 56, Pages: 804-868, ISSN: 0570-4928
Analytical technologies that can improve disease diagnosis are highly sought after. Current screening/diagnostic tests for several diseases are limited by their moderate diagnostic performance, invasiveness, costly and laborious methodologies or the need for multiple tests before a definitive diagnosis. Spectroscopic techniques, including infrared (IR) and Raman, have attracted great interest in the medical field, with applications expanding from early disease detection to monitoring and real-time diagnosis. This review highlights applications of IR and Raman spectroscopy, with a focus on cancer and infectious diseases since 2015, and underscores the diverse sample types that can be analyzed, such as biofluids, cells and tissues. Studies involving more than 25 participants per group (disease and control group; if no control group >25 in disease group) were considered eligible, to retain the clinical focus of the paper. Following literature searches, we identified 94 spectroscopic studies on different cancers and 30 studies on infectious diseases. The review suggests that such technologies have the potential to develop into an objective, inexpensive, point-of-care test or facilitate disease diagnosis and monitoring. Up-to-date considerations for the implementation of spectroscopic techniques into a clinical setting, health economics and successful applications of vibrational spectroscopic tests in the clinical arena are also discussed.
Kechagias K, Katsikas-Triantafyllidis K, Kyriakidou M, et al., 2021, The relation between caffeine consumption and endometriosis: An updated systematic review and meta-analysis, Nutrients, Vol: 13, Pages: 1-12, ISSN: 2072-6643
While the contributing factors leading to endometriosis remain unclear, its clinical heterogeneity suggests a multifactorial causal background. Amongst others, caffeine has been studied extensively during the last decade as a putative contributing factor. In this systematic review and meta-analysis, we provide an overview/critical appraisal of studies that report on the association between caffeine consumption and the presence of endometriosis. In our search strategy, we screened PubMed and Scopus for human studies examining the above association. The main outcome was the relative risk of endometriosis in caffeine users versus women consuming little or no caffeine (<100 mg/day). Subgroup analyses were conducted for different levels of caffeine intake: high (>300 mg/day) or moderate (100–300 mg/day). Ten studies were included in the meta-analysis (five cohort and five case-control studies). No statistically significant association was observed between overall caffeine consumption and risk for endometriosis (RR 1.12, 95% confidence interval (CI) 0.97–1.28, I2 = 70%) when compared to little or no (<100 mg/day) caffeine intake. When stratified according to level of consumption, high intake was associated with increased risk of endometriosis (RR 1.30, 95%CI 1.04–1.63, I2 = 56%), whereas moderate intake did not reach nominal statistical significance (RR 1.18, 95%CI 0.99–1.40, I2 = 37%). In conclusion, caffeine consumption does not appear to be associated with increased risk for endometriosis. However, further research is needed to elucidate the potential dose-dependent link between caffeine and endometriosis or the probable role of caffeine intake as a measurement of other unidentified biases.
Mitra A, MacIntyre D, Paraskevaidi M, et al., 2021, The vaginal microbiota and innate Immunity after local excisional treatment for cervical intraepithelial neoplasia, Publisher: BioMed Central
Background: Vaginal microbiota (VMB) are altered in women with cervical intra-epithelial neoplasia (CIN) and associate with disease progression. However, the impact of CIN excision on the VMB and innate immunity is not known. This interventional study aims to explore the impact of CIN excision on the VMB, antimicrobial peptides (AMP) and proinflammatory cytokines. We sampled 103 non-pregnant, premenopausal women at the time of excisional treatment for CIN and at their 6-month follow-up visit. A further 39 untreated controls with normal cytology were also sampled. We used metataxonomics to group vaginal swab samples into community state types (CSTs) and ELISA to quantify cytokine and AMPs levels in matched vaginal secretions. Analyses were performed to compare bacterial composition and immune analyte levels before and after CIN excision and in healthy controls.Results: Women with CIN had significantly higher rates of Lactobacillus species depletion pre-treatment compared to healthy controls (CST IV: 21/103, 20% vs 1/39, 3%, p=0.0081). Excision did not change the VMB composition, with CST IV remaining significantly more prevalent after excision compared to untreated, healthy controls (CST IV: 19/103, 20% vs 1/39, 3%, p=0.0142). Prevotella bivia and Sneathia amnii were significantly higher in samples before treatment compared to untreated controls and Prevotella bivia remained significantly higher amongst the treated, with less Lactobacillus crispatus compared to untreated controls. IL-1 and IL-8 remained significantly elevated pre- (p<0.0001 and p=0.0014 respectively) and post-treatment compared to untreated controls (p<0.0001 and p=0.0035 respectively). Levels of human beta-defensin-1 and secretory leukocyte protease inhibitor were both significantly reduced following CIN excision (p<0.0001), however their levels remained lower than controls post-treatment.Conclusions: Women with CIN have increased prevalence of Lactobacillus spp. depleted, high-diversity V
Kyrgiou M, Bowden SJ, Athanasiou A, et al., 2021, Morbidity after local excision of the transformation zone for cervical intra-epithelial neoplasia and early cervical cancer, Best Practice and Research: Clinical Obstetrics and Gynaecology, Vol: 75, Pages: 10-22, ISSN: 1521-6934
The awareness that cervical intra-epithelial neoplasia (CIN) treatment increases the risk of preterm birth has led to major changes in clinical practice. Women with CIN have a higher baseline risk of prematurity but local treatment further increases this risk. The risk further increases with increasing cone length and multiplies for repeat excisions; it is unclear whether small cones confer any additional risk to CIN alone. There is no evidence to suggest that fertility is affected by local treatment, although this increases the risk of mid-trimester loss. Caution should prevail when deciding to treat women with CIN of reproductive age. If treatment is offered, this should be conducted effectively to optimise the clearance of disease and minimise the risk of recurrence. Colposcopists should alert women undergoing treatment that this may increase the risk of preterm birth and that they may be offered interventions when pregnant. The cone length should be clearly documented and used as a risk stratifier.
Paraskevaidis E, Athanasiou A, Kalliala I, et al., 2021, Invasive cervical cancer following treatment of pre-invasive lesions: A potential theory based on a small case series, European Journal of Obstetrics Gynecology and Reproductive Biology, Vol: 264, Pages: 56-59, ISSN: 0301-2115
PURPOSE: The aim of this study is to present a single department's experience on cervical cancer cases following previous excision of cervical intraepithelial neoplasia (CIN) and to discuss potential pathogenesis. METHODS: Nine cervical cancer cases meeting the inclusion criteria, with available pathological and follow-up data, were considered eligible for this study. RESULTS: The majority (7/9) have had clear excisional margins. The interval between initial treatment and cancer diagnosis ranged from 7 to 17 years. In all cases cancer diagnosis was "unexpected", as the prior cytological and/or colposcopic evaluation was not suggestive of significant cervical pathology. All cancers were squamous, and 5/9 at stage I. CONCLUSION: The long interval between initial CIN treatment and final diagnosis as well as the normal post-treatment follow-up may suggest a 'de novo' underlying but 'hidden' carcinogenesis process. It might be that dysplastic cells entrapped within crypts (or normal metaplastic affected by the same predisposing factors) continue undergoing their evolution, undetectable by cytology and colposcopy until they invade stroma and surfaces (endo- and/or ectocervical) approximately a decade later. Heavy cauterisation of cervical crater produced post excision might be a potential culprit of this entrapment.
Luo Y, Liu H, Wu C, et al., 2021, Diagnostic segregation of human breast tumours using Fourier-transform infrared spectroscopy coupled with multivariate analysis: Classifying cancer subtypes, SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY, Vol: 255, ISSN: 1386-1425
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Kechagias KS, Semertzidou A, Athanasiou A, et al., 2020, Bisphenol-A and polycystic ovary syndrome: a review of the literature, Reviews on Environmental Health, Vol: 35, Pages: 323-331, ISSN: 0048-7554
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age with reproductive, metabolic and endocrine implications. While the exact pathophysiological mechanisms of the syndrome are unknown, its heterogeneity suggests a multifactorial causal background. In the last two decades, numerous environmental chemicals, including Bisphenol-A (BPA) that is used in the synthesis of polycarbonate plastics, have been proposed as potential contributors to the aetiology of PCOS. This review provides a holistic overview of the available data regarding the possible relation of PCOS with BPA exposure. We have included a total number of 24 studies. Eleven human case-control and 13 animal studies provided data regarding this potential relation. Accumulating evidence suggests that a correlation between high levels of BPA and the presence of PCOS may exist. Contradicting results from human and animal studies, however, render it difficult to conclude on the exact role of BPA in the pathogenesis of PCOS. BPA may constitute a consequence of the syndrome rather than a cause, but further research is still needed to clarify this. Continued efforts to study the early origins of PCOS, using prospective-designed studies, are required to identify the exact effect of BPA on women with PCOS.
Paraskevaidi M, Cameron SJS, Whelan E, et al., 2020, Laser-assisted rapid evaporative ionisation mass spectrometry (LA-REIMS) as a metabolomics platform in cervical cancer screening, EBioMedicine, Vol: 60, ISSN: 2352-3964
BackgroundThe introduction of high-risk human papillomavirus (hrHPV) testing as part of primary cervical screening is anticipated to improve sensitivity, but also the number of women who will screen positive. Reflex cytology is the preferred triage test in most settings but has limitations including moderate diagnostic accuracy, lack of automation, inter-observer variability and the need for clinician-collected sample. Novel, objective and cost-effective approaches are needed.MethodsIn this study, we assessed the potential use of an automated metabolomic robotic platform, employing the principle of laser-assisted Rapid Evaporative Ionisation Mass Spectrometry (LA-REIMS) in cervical cancer screening.FindingsIn a population of 130 women, LA-REIMS achieved 94% sensitivity and 83% specificity (AUC: 91.6%) in distinguishing women testing positive (n = 65) or negative (n = 65) for hrHPV. We performed further analysis according to disease severity with LA-REIMS achieving sensitivity and specificity of 91% and 73% respectively (AUC: 86.7%) in discriminating normal from high-grade pre-invasive disease.InterpretationThis automated high-throughput technology holds promise as a low-cost and rapid test for cervical cancer screening and triage. The use of platforms like LA-REIMS has the potential to further improve the accuracy and efficiency of the current national screening programme.
Tzafetas M, Mitra A, Paraskevaidi M, et al., 2020, The intelligent knife (iKnife) and its intraoperative diagnostic advantage for the treatment of cervical disease (vol 117, pg 7338, 2020), PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 117, Pages: 18892-18892, ISSN: 0027-8424
Paraskevaidi M, Allsop D, Karim S, et al., 2020, Diagnostic biomarkers for Alzheimer's disease using non-invasive specimens, Journal of Clinical Medicine, Vol: 9, Pages: 1-19, ISSN: 2077-0383
Studies in the field of Alzheimer’s disease (AD) have shown the emergence of biomarkers in biologic fluids that hold great promise for the diagnosis of the disease. A diagnosis of AD at a presymptomatic or early stage may be the key for a successful treatment, with clinical trials currently investigating this. It is anticipated that preventative and therapeutic strategies may be stage-dependent, which means that they have a better chance of success at a very early stage—before critical neurons are lost. Several studies have been investigating the use of cerebrospinal fluid (CSF) and blood as clinical samples for the detection of AD with a number of established core markers, such as amyloid beta (Aβ), total tau (T-tau) and phosphorylated tau (P-tau), being at the center of clinical research interest. The use of oral samples—including saliva and buccal mucosal cells—falls under one of the least-investigated areas in AD diagnosis. Such samples have great potential to provide a completely non-invasive alternative to current CSF and blood sampling procedures. The present work is a thorough review of the results and analytical approaches, including proteomics, metabolomics, spectroscopy and microbiome analyses that have been used for the study and detection of AD using salivary samples and buccal cells. With a few exceptions, most of the studies utilizing oral samples were performed in small cohorts, which in combination with the existence of contradictory results render it difficult to come to a definitive conclusion on the value of oral markers. Proteins such as Aβ, T-tau and P-tau, as well as small metabolites, were detected in saliva and have shown some potential as future AD diagnostics. Future large-cohort studies and standardization of sample preparation and (pre-)analytical factors are necessary to determine the use of these non-invasive samples as a diagnostic tool for AD.
Paraskevaidi M, Morais CLM, Ashton KM, et al., 2020, Detecting endometrial cancer by blood spectroscopy: a diagnostic cross-sectional study, Cancers, Vol: 12, Pages: 1-17, ISSN: 2072-6694
Endometrial cancer is the sixth most common cancer in women, with a rising incidence worldwide. Current approaches for the diagnosis and screening of endometrial cancer are invasive, expensive or of moderate diagnostic accuracy, limiting their clinical utility. There is a need for cost-effective and minimally invasive approaches to facilitate the early detection and timely management of endometrial cancer. We analysed blood plasma samples in a cross-sectional diagnostic accuracy study of women with endometrial cancer (n = 342), its precursor lesion atypical hyperplasia (n = 68) and healthy controls (n = 242, total n = 652) using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and machine learning algorithms. We show that blood-based infrared spectroscopy has the potential to detect endometrial cancer with 87% sensitivity and 78% specificity. Its accuracy is highest for Type I endometrial cancer, the most common subtype, and for atypical hyperplasia, with sensitivities of 91% and 100%, and specificities of 81% and 88%, respectively. Our large-cohort study shows that a simple blood test could enable the early detection of endometrial cancer of all stages in symptomatic women and provide the basis of a screening tool in high-risk groups. Such a test has the potential not only to differentially diagnose endometrial cancer but also to detect its precursor lesion atypical hyperplasia—the early recognition of which may allow fertility sparing management and cancer prevention.
Athanasiou A, Bowden S, Paraskevaidi M, et al., 2020, HPV vaccination and cancer prevention, Best Practice and Research: Clinical Obstetrics and Gynaecology, Vol: 65, Pages: 109-124, ISSN: 1521-6934
Prophylactic vaccines have been found to be highly effective in preventing infection and pre-invasive and invasive cervical, vulvovaginal and anal disease caused by the vaccine types. HPV vaccines contain virus-like particles that lack the viral genome and produce high titres of neutralising antibodies. Although the vaccines are highly effective in preventing infections, they do not enhance clearance of existing infections. Vaccination programmes target prepubertal girls and boys prior to sexual debut as efficacy is highest in HPV naïve individuals. School-based programmes achieve higher coverage, although implementation is country specific. Vaccination of older women may offer some protection and acceleration of impact, although this may not be cost-effective. HPV-based screening will continue for vaccinated cohorts, although intervals may increase.
Paraskevaidis E, Athanasiou A, Paraskevaidi M, et al., 2020, Cervical pathology following HPV vaccination in Greece: A 10-year HeCPA observational cohort study, In Vivo: international journal of experimental and clinical pathophysiology and drug research, Vol: 34, Pages: 1445-1449, ISSN: 0258-851X
Background: In Greece the population-level impact of HPV vaccination is unknown due to lacking official registries. This study presents in a pragmatic frame the comparison of cervical pathology data between HPV-vaccinated and unvaccinated women referred for colposcopy.Materials and Methods: This is an observational prospective cohort study performed in 7 academic Obstetrics & Gynaecology departments across Greece between 2009-2019. Cases were women that had completed HPV vaccination before coitarche and were referred for colposcopy due to abnormal cytology. For each vaccinated woman an unvaccinated matched control was selected. Results: A total of 849 women who had been vaccinated before coitarche and 849 unvaccinated controls were recruited. The combination of cytological, colposcopic and molecular findings necessitated treatment in only a single case among vaccinated (0.1%) and in 8.4% among unvaccinated. Conclusion: Despite potential bias, this study’s message is clear: HPV vaccination at a proper age can markedly reduce development of severe cervical precancer and consequently, the need for treatments with their long-term related obstetrical morbidity.
Tzafetas M, Mitra A, Paraskevaidi M, et al., 2020, The intelligent-Knife (i-Knife) and its intraoperative diagnostic advantage for the treatment of cervical disease, Proceedings of the National Academy of Sciences of USA, Vol: 117, Pages: 7338-7346, ISSN: 0027-8424
Clearance of surgical margins in cervical cancer prevents the need for adjuvant chemoradiation and allows fertility preservation. In this study, we determined the capacity of the rapid evaporative ionization mass spectrometry (REIMS), also known as intelligent knife (iKnife), to discriminate between healthy, preinvasive, and invasive cervical tissue. Cervical tissue samples were collected from women with healthy, human papilloma virus (HPV) ± cervical intraepithelial neoplasia (CIN), or cervical cancer. A handheld diathermy device generated surgical aerosol, which was transferred into a mass spectrometer for subsequent chemical analysis. Combination of principal component and linear discriminant analysis and least absolute shrinkage and selection operator was employed to study the spectral differences between groups. Significance of discriminatory m/z features was tested using univariate statistics and tandem MS performed to elucidate the structure of the significant peaks allowing separation of the two classes. We analyzed 87 samples (normal = 16, HPV ± CIN = 50, cancer = 21 patients). The iKnife discriminated with 100% accuracy normal (100%) vs. HPV ± CIN (100%) vs. cancer (100%) when compared to histology as the gold standard. When comparing normal vs. cancer samples, the accuracy was 100% with a sensitivity of 100% (95% CI 83.9 to 100) and specificity 100% (79.4 to 100). Univariate analysis revealed significant MS peaks in the cancer-to-normal separation belonging to various classes of complex lipids. The iKnife discriminates healthy from premalignant and invasive cervical lesions with high accuracy and can improve oncological outcomes and fertility preservation of women treated surgically for cervical cancer. Larger in vivo research cohorts are required to validate these findings.
Kalliala I, Athanasiou A, Veroniki AA, et al., 2020, Incidence and mortality from cervical cancer and other malignancies after treatment of cervical intraepithelial neoplasia: a systematic review and meta-analysis of the literature., Annals of Oncology, Vol: 31, Pages: 213-227, ISSN: 0923-7534
Background: While local treatments for cervical intraepithelial neoplasia (CIN) are highly effective, it has been reported that treated women remain at increased risk of cervical and other cancers. Our aim is to explore the risk of developing or dying from cervical cancer and other HPV- and non-HPV-related malignancies after CIN treatment and infer about its magnitude compared to general population.Materials and methods:Design: Systematic review and meta-analysis.Eligibility criteria: Studies with registry-based follow-up reporting cancer incidence or mortality after CIN treatment. Data synthesis: Summary effects were estimated using random-effects models.Outcomes: Incidence rate of cervical cancer among women treated for CIN (per 100,000 woman-years). Relative risk (RR) of cervical cancer, other HPV-related anogenital tract cancer (vagina, vulva, anus), any cancer, and mortality, for women treated with CIN versus the general population.Results: Twenty-seven studies were eligible. The incidence rate for cervical cancer after CIN treatment was 39 per 100,000 woman-years (95% CI 22 to 69). RR of cervical cancer was elevated compared to the general population (3·30, 2·57 to 4·24; P<0·001). RR was higher for women over 50 years old and remained elevated for at least 20 years after treatment. RR of vaginal (10·84, 5·58 to 21·10; P<0·001), vulvar (3·34, 2·39 to 4·67; P<0·001), and anal cancer (5·11, 2·73 to 9·55; P<0·001) was also higher. Mortality from cervical/vaginal cancer was elevated, but our estimate was more uncertain (RR 5·04, 0·69 to 36·94; P=0·073).Conclusions: Women treated for CIN have considerably higher risk to be later diagnosed with cervical and other HPV-related cancers compared to general population. The higher risk of cervical cancer lasts for at least 20 years after treatment and is higher for women
Paraskevaidi M, Hook PD, Morais CLM, et al., 2020, Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy to diagnose osteoarthritis in equine serum, EQUINE VETERINARY JOURNAL, Vol: 52, Pages: 46-51, ISSN: 0425-1644
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