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Whelan E, Kalliala I, Semertzidou A, et al., 2022, Risk Factors for Ovarian Cancer: An Umbrella Review of the Literature, Cancers, Vol: 14, Pages: 2708-2708
<jats:p>Several non-genetic factors have been associated with ovarian cancer incidence or mortality. To evaluate the strength and validity of the evidence we conducted an umbrella review of the literature that included systematic reviews/meta-analyses that evaluated the link between non-genetic risk factors and ovarian cancer incidence and mortality. We searched PubMed, EMBASE, Cochrane Database of Systematic Reviews and performed a manual screening of references. Evidence was graded into strong, highly suggestive, suggestive or weak based on statistical significance of the random effects summary estimate and the largest study in a meta-analysis, the number of cases, between-study heterogeneity, 95% prediction intervals, small study effects, and presence of excess significance bias. We identified 212 meta-analyses, investigating 55 non-genetic risk factors for ovarian cancer. Risk factors were grouped in eight broad categories: anthropometric indices, dietary intake, physical activity, pre-existing medical conditions, past drug history, biochemical markers, past gynaecological history and smoking. Of the 174 meta-analyses of cohort studies assessing 44 factors, six associations were graded with strong evidence. Greater height (RR per 10 cm 1.16, 95% confidence interval (CI) 1.11–1.20), body mass index (BMI) (RR ≥ 30 kg/m2 versus normal 1.27, 95% CI 1.17–1.38) and three exposures of varying preparations and usage related to hormone replacement therapy (HRT) use increased the risk of developing ovarian cancer. Use of oral contraceptive pill reduced the risk (RR 0.74, 95% CI 0.69–0.80). Refining the significance of genuine risk factors for the development of ovarian cancer may potentially increase awareness in women at risk, aid prevention and early detection.</jats:p>
Doulgeraki T, Bowden S, Athanasiou A, et al., 2022, Environmental and modifiable risk factors for cervical cancer: An umbrella review, Publisher: ELSEVIER, Pages: E83-E83, ISSN: 0301-2115
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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.
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
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.
Rockall A, Barwick T, Wilson W, et al., 2021, Diagnostic accuracy of FEC-PET/CT, FDG-PET/CT and diffusion-weighted MRI in detection of nodal metastases in surgically treated endometrial and cervical carcinoma, Clinical Cancer Research, Vol: 27, Pages: 6457-6466, ISSN: 1078-0432
Purpose:Pre-operative nodal staging is important for planning treatment in cervical cancer (CC) and endometrial cancer (EC) but remains challenging. We compare nodal staging accuracy of 18F-ethyl-choline-(FEC)-PET/CT, 18F-Fluoro-deoxy-glucose-(FDG)-PET/CT and diffusion-weighted-MRI (DW-MRI) with conventional morphological MRI.Experimetal Design:A prospective, multicentre observational study of diagnostic accuracy for nodal metastases was undertaken in 5 gyne-oncology centres. FEC-PET/CT, FDG-PET/CT and DW-MRI were compared to nodal size and morphology on MRI. Reference standard was strictly correlated nodal histology. Eligibility included operable CC stage=>1B1 or EC (grade 3 any stage with myometrial invasion or grade 1-2 stage=>II). Results:Among 162 consenting participants, 136 underwent study DW-MRI and FDG-PET/CT, and 60 underwent FEC-PET/CT. 267 nodal regions in 118 women were strictly correlated at histology (nodal positivity rate 25%). Sensitivity per-patient (n=118) for nodal size, morphology, DW-MRI, FDG- and FEC-PET/CT were 40%*, 53%, 53%, 63%* and 67% for all cases (*p=0.016); 10%, 10%, 20%, 30% and 25% in CC (n=40); 65%, 75%, 70%, 80% and 88% in EC (n=78). FDG-PET/CT outperformed nodal size (p=0.006) and size ratio (p=0.04) for per-region sensitivity. False positive rates were all <10%. Conclusions:All imaging techniques had low sensitivity for detection of nodal metastases and cannot replace surgical nodal staging. The performance of FEC-PET/CT was not statistically different to other techniques that are more widely available. FDG-PET/CT had higher sensitivity than size in detecting nodal metastases. False positive rates were low across all methods. The low false positive rate demonstrated by FDG-PET/CT may be helpful in arbitration of challenging surgical planning decisions.
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.
Lythgoe M, Adriani M, Stebbing J, et al., 2021, 543P Neoadjuvant MRx0518 treatment is associated with significant gene and metagene signature changes in solid tumours, Annals of Oncology, Vol: 32, Pages: S607-S607, ISSN: 0923-7534
BackgroundMRx0518 is an oral live biotherapeutic with potent immunostimulatory activity and anti-tumorigenic efficacy in murine models of lung (LLC1), kidney (Renca) and breast (EMT6) cancer. Previous reports have demonstrated a favourable safety profile in neoadjuvant and metastatic clinical settings, with emerging evidence of immune modulation. We performed a comprehensive analysis of the gene and metagene signature in cancer patients treated with MRx0518 monotherapy.MethodsTreatment-naïve patients with a histologically confirmed diagnosis of cancer scheduled for surgical resection were recruited from April 2019 to February 2020. Patients received 1 capsule of MRx0518 (1x1010 to 1x1011CFU) twice daily from inclusion until the day preceding surgery. Safety and tolerability (CTCAE v4.03) were the primary endpoints of this study. Comprehensive biomarker analysis was also performed in paired pre-treatment (diagnostic biopsy) and post-treatment (surgical specimen) samples using the NanoString IO 360 panel to explore gene and metagene signatures.Results31 samples were collected across tumour groups including breast (n=13) prostate (n=8), uterine (n=6), melanoma (n=2) and bladder (n=2). Differential expression analysis showed significant (p<0.05) increases in genes and metagenes associated with anti-tumour activity, including antigen presentation (AXL & CXCL12), innate immune processes (CHUK, RELA, PPARG & HRAS), interferon response (IFNGR1 & IFNGR2), Th1 cells and CD8+ cells following MRx0518 therapy, echoing preclinical findings. Novel changes, not previously detected in murine models, involving endothelial, mast cells, inflammatory myeloid and inflammatory chemokines were also observed, suggesting MRx0518 may have additional in vivo anti-tumorigenic effects. These changes were more pronounced in the breast cancer cohort.ConclusionsThis analysis, mirrors previous immunostimulatory activity and anti-tumorigenic efficacy observations seen in pre-clini
Tsilidis K, 2021, An umbrella review of the evidence associating diet and cancer risk at 11 anatomical sites, Nature Communications, Vol: 12, Pages: 1-10, ISSN: 2041-1723
There is evidence that diet and nutrition are modifiable risk factors for several cancers, but associations may be flawed due to inherent biases. Nutritional epidemiology studies have largely relied on a single assessment of diet using food frequency questionnaires. We conduct an umbrella review of meta-analyses of observational studies to evaluate the strength and validity of the evidence for the association between food/nutrient intake and risk of developing or dying from 11 primary cancers. It is estimated that only few single food/nutrient and cancer associations are supported by strong or highly suggestive meta-analytic evidence, and future similar research is unlikely to change this evidence. Alcohol consumption is positively associated with risk of postmenopausal breast, colorectal, esophageal, head & neck and liver cancer. Consumption of dairy products, milk, calcium and wholegrains are inversely associated with colorectal cancer risk. Coffee consumption is inversely associated with risk of liver cancer and skin basal cell carcinoma.
Athanasiou A, Bowden SJ, Paraskevaidis E, et al., 2021, Neoadjuvant chemotherapy and surgery versus chemoradiotherapy for locally advanced cervical cancer, Cochrane Database of Systematic Reviews, Vol: 2021, ISSN: 1465-1858
Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. The aim of this review is to compare neoadjuvant chemotherapy (NACT) followed by radical surgery (RS) versus chemoradiotherapy (CRT) for locally advanced cervical cancer.
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.
Pearson-Stuttard J, Papadimitriou N, Markozannes G, et al., 2021, Type 2 diabetes and cancer: an umbrella review of observational and Mendelian randomisation studies, Cancer Epidemiology, Biomarkers and Prevention, Vol: 30, Pages: 1218-1228, ISSN: 1055-9965
Background Type 2 diabetes(T2DM) has been associated with an increased risk of developing several common cancers, but it is unclear whether this association is causal. We aimed to summarise the evidence on T2DM and cancer and evaluate the validity of associations from both observational and Mendelian randomisation(MR) studies. Methods We performed an umbrella review of the evidence across meta-analyses of observational studies that examined associations of T2DM with risk of developing or dying from site-specific cancers, and MR studies that explored the potential causal association of T2DM and associated biomarkers with cancer risk. Results We identified eligible observational meta-analyses that assessed associations between T2DM and cancer incidence for 18 cancer sites, cancer mortality for seven sites, and cancer incidence or mortality for four sites. Positive associations between T2DM and six cancers reached strong or highly suggestive evidence. We found eight MR studies assessing the association of genetically predicted T2DM and seven and eight studies assessing the association of genetically predicted fasting insulin or fasting glucose concentrations, respectively, upon site-specific cancers. Positive associations were found between genetically predicted T2DM and fasting insulin and risk of six cancers. There was no association between genetically predicted fasting plasma glucose and cancer except for squamous cell lung carcinoma. Conclusions We found robust observational evidence for the association between T2DM and colorectal, hepatocellular, gallbladder, breast, endometrial and pancreatic cancer. Impact Potential causal associations were identified for genetically predicted T2DM and fasting insulin concentrations and risk of endometrial, pancreas, kidney, breast, lung and cervical cancer.
Semertzidou A, MacIntyre D, Marchesi J, et al., 2021, The role of genital tract microbiota continuum in endometrial malignancy, Publisher: WILEY, Pages: 115-116, ISSN: 1470-0328
Semertzidou A, Grout-Smith H, Kalliala I, et al., 2021, Diabetes and the risk of gynaecological and obstetric outcomes: an umbrella review, Publisher: WILEY, Pages: 36-37, ISSN: 1470-0328
Raglan O, MacIntyre D, Mitra A, et al., 2021, The association between obesity and weight loss after bariatric surgery on the vaginal microbiota, Microbiome, Vol: 9, Pages: 1-17, ISSN: 2049-2618
Background: Obesity and vaginal microbiome (VMB) dysbiosis are each risk factors for adverse reproductive and oncological health outcomes in women. Here we investigated the relationship between obesity, vaginal bacterial composition, local inflammation and bariatric surgery.Methods: Vaginal bacterial composition assessed by high-throughput sequencing of bacterial 16S rRNA genes and local cytokine levels measured using a multiplexed Magnetic Luminex Screening Assay were compared between 67 obese and 42 non-obese women. We further assessed temporal changes in the microbiota and cytokines in a subset of 27 women who underwent bariatric surgery. Results: The bacterial component of the vaginal microbiota in obese women was characterised by a lower prevalence of a Lactobacillus-dominant VMB and higher prevalence of a high diversity (Lactobacillus spp., and Gardnerella- spp. depleted) VMB, compared with non-obese subjects (p<0.001). Obese women had higher relative abundance of Dialister species (p<0.001), Anaerococcus vaginalis (p=0.021) and Prevotella timonensis (p=0.020) and decreased relative abundance of Lactobacillus crispatus (p=0.014). Local vaginal IL-1β, IL-4, IL-6, IL-8, IFNγ, MIP-1α, and TNFα levels were all higher among obese women, however only IL-1β and IL-8 correlated with VMB species diversity. In a subset of obese women undergoing bariatric surgery, there were no significant overall differences in VMB following surgery, however 75% of these women remained obese at six months. Prior to surgery there was no relationship between body mass index (BMI) and VMB structure, however post-surgery women with a Lactobacillus-dominant VMB had a significantly lower BMI than those with a high diversity VMB.Conclusions: Obese women have a significantly different vaginal microbiota composition with increased levels of local inflammation compared to non-obese women. Bariatric surgery does not change the VMB, however, those with the greatest
Raglan O, MacIntyre D, Mitra A, et al., 2021, The association between obesity and weight loss after bariatric surgery on the vaginal microbiota, Microbiome, ISSN: 2049-2618
<h4>Background: </h4> Obesity and vaginal microbiome (VMB) dysbiosis are each risk factors for adverse reproductive and oncological health outcomes in women. Here we investigated the relationship between obesity, vaginal bacterial composition, local inflammation and bariatric surgery. <h4>Methods: </h4>: Vaginal bacterial composition assessed by high-throughput sequencing of bacterial 16S rRNA genes and local cytokine levels measured using a multiplexed Magnetic Luminex Screening Assay were compared between 67 obese and 42 non-obese women. We further assessed temporal changes in the microbiota and cytokines in a subset of 27 women who underwent bariatric surgery. <h4>Results: </h4>: The bacterial component of the vaginal microbiota in obese women was characterised by a lower prevalence of a Lactobacillus -dominant VMB and higher prevalence of a high diversity ( Lactobacillus spp., and Gardnerella - spp. depleted) VMB, compared with non-obese subjects (p<0.001). Obese women had higher relative abundance of Dialister species (p<0.001), Anaerococcus vaginalis (p=0.021) and Prevotella timonensis (p=0.020) and decreased relative abundance of Lactobacillus crispatus (p=0.014). Local vaginal IL-1β, IL-4, IL-6, IL-8, IFNγ, MIP-1α, and TNFα levels were all higher among obese women, however only IL-1β and IL-8 correlated with VMB species diversity. In a subset of obese women undergoing bariatric surgery, there were no significant overall differences in VMB following surgery, however 75% of these women remained obese at six months. Prior to surgery there was no relationship between body mass index (BMI) and VMB structure, however post-surgery women with a Lactobacillus -dominant VMB had a significantly lower BMI than those with a high diversity VMB. <h4>Conclusions: </h4>: Obese women have a significantly different vaginal microbiota composition with increased levels of local inflammation compare
Bowden S, Bodinier B, Kalliala I, et al., 2021, Genetic variation in cervical preinvasive and invasive disease: a genome-wide association study, The Lancet Oncology, Vol: 22, Pages: 548-557, ISSN: 1213-9432
Background: Most uterine cervical high-risk HPV infections (hrHPV) are transient, with only a small 3fraction developing into cervical cancer. Family aggregation studies and heritability estimates suggest 4a significant inherited genetic component. Candidate gene studies and previous genome-wide 5association studies (GWAS) report associations between the human leukocyte antigen (HLA) region 6and cervical cancer. 78Methods: Adopting a genome-wide approach, we compared the genetic variation in women with 9invasive cervical cancer (ICC) and cervical intra-epithelial neoplasia (CIN) grade 3, to that in healthy 10controls using the largest reported cohort of unrelated European individuals (N=150,314)to date. We 11sought for replication in a second large independent dataset (N=128,123). We further performed a two-12sample Mendelian Randomisation approach to explore the role of risk factors in the genetic risk of 13cervical cancer.1415Findings: In our analysis (N=4,769 CIN3 and ICC cases; N=145,545 controls), of the (N=9,600,464) 16assayed and imputed SNPs, six independent variants were found associated with CIN3and ICC. These 17included novel loci rs10175462(PAX8; OR=0.87(95%CI=0.84-0.91); P=1.07x10-9) and rs27069 18(CLPTM1L;OR=0.88(95%CI=0.84-0.92); P=2.51x10-9), and previously reported signals at rs9272050 19(HLA-DQA1;OR=1.27(95%CI=1.21-1.32); P=2.51x10-28), rs6938453 (MICA;OR=0.7920(95%CI=0.75-0.83); P=1.97x10-17), rs55986091 (HLA-DQB1;OR=0.66(95%CI=0.60-0.72); 21P=6.42x10-22) and rs9266183 (HLA-B;OR=0.73(95%CI=0.64-0.83); P=1.53x10-6). Mendelian 22randomisation further supported the complementary role of smoking, age at first pregnancy, and number 23of sexual partners in the risk of developing cervical cancer.2425Interpretation: Our results provide substantial new evidence for genetic susceptibility to cervical cancer, 26including PAX8, CLPTM1LandHLA genes, suggesting disruption in apoptotic and immun
Weyers S, Garland SM, Cruickshank M, et al., 2021, Cervical cancer prevention in transgender men: a review, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 128, Pages: 822-826, ISSN: 1470-0328
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Tsonis O, Diakaki K, Gkrozou F, et al., 2021, Psychological burden of covid-19 health crisis on health professionals and interventions to minimize the effect: what has history already taught us?, RIVISTA DI PSICHIATRIA, Vol: 56, Pages: 57-63, ISSN: 0035-6484
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Semertzidou A, Macintyre D, Marchesi J, et al., 2021, THE ROLE OF GENITAL TRACT MICROBIOTA CONTINUUM IN ENDOMETRIAL MALIGNANCY, Publisher: BMJ PUBLISHING GROUP, Pages: A135-A135, ISSN: 1048-891X
Bowden SJ, Lathouras K, Kyrgiou M, 2021, Can DNA methylation tests improve the accuracy of cervical screening?, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 128, Pages: 515-515, ISSN: 1470-0328
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Arbyn M, Gultekin M, Morice P, et al., 2021, The European response to theWHOcall to eliminate cervical cancer as a public health problem, INTERNATIONAL JOURNAL OF CANCER, Vol: 148, Pages: 277-284, ISSN: 0020-7136
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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.
Semertzidou A, Brosens JJ, McNeish I, et al., 2020, Organoid models in gynaecological oncology research, CANCER TREATMENT REVIEWS, Vol: 90, ISSN: 0305-7372
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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.
Kyrgiou M, Arbyn M, Bergeron C, et al., 2020, Cervical screening: ESGO-EFC position paper of the European Society of Gynaecologic Oncology (ESGO) and the European Federation of Colposcopy (EFC), BRITISH JOURNAL OF CANCER, Vol: 123, Pages: 510-517, ISSN: 0007-0920
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- Citations: 58
Mnimatidis P, Pouliakis A, Valasoulis G, et al., 2020, Multicentric assessment of cervical HPV infection co-factors in a large cohort of Greek women, EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY, Vol: 41, Pages: 545-555, ISSN: 0392-2936
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- Citations: 2
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
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