Imperial College London

Dr Maria Kyrgiou

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Clinical Professor of Gynaecological Oncology
 
 
 
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Contact

 

+44 (0)20 7594 2177m.kyrgiou Website

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

201 results found

Kyrgiou M, Bowden SJ, Athanasiou A, Paraskevaidi M, Kechagias K, Zikopoulos A, Terzidou V, Martin-Hirsch P, Arbyn M, Bennett P, Paraskevaidis Eet 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.

Journal article

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.

Journal article

Athanasiou A, Bowden SJ, Paraskevaidis E, Shylasree TS, Lathouras K, Kyrgiou Met 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.

Journal article

Paraskevaidis E, Athanasiou A, Kalliala I, Batistatou A, Paraskevaidi M, Bilirakis E, Nasioutziki M, Paschopoulos M, Lyons D, Arbyn M, Cruickshank M, Martin-Hirsch P, Kyrgiou Met 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.

Journal article

Pearson-Stuttard J, Papadimitriou N, Markozannes G, Cividini S, Kakourou A, Gill D, Rizos EC, Monori G, Ward HA, Kyrgiou M, Gunter MJ, Tsilidis KKet 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.

Journal article

Semertzidou A, Grout-Smith H, Kalliala I, Kyrgiou Met al., 2021, Diabetes and the risk of gynaecological and obstetric outcomes: an umbrella review, Publisher: WILEY, Pages: 36-37, ISSN: 1470-0328

Conference paper

Semertzidou A, MacIntyre D, Marchesi J, Bennett P, Kyrgiou Met al., 2021, The role of genital tract microbiota continuum in endometrial malignancy, Publisher: WILEY, Pages: 115-116, ISSN: 1470-0328

Conference paper

Whelan E, Kalliala I, Semertzidou A, Raglan O, Bowden S, Markozannes G, Cividini S, Kechagias K, McNeish I, Marchesi J, MacIntyre D, Bennett P, Tsilidis K, Kyrgiou Met al., 2021, Risk factors for ovarian cancer: an umbrella review of the literature, Publisher: WILEY, Pages: 71-71, ISSN: 1470-0328

Conference paper

Raglan O, MacIntyre D, Mitra A, Lee YS, Smith A, Assi N, Nautiyal J, Purkayastha S, Gunter MJ, Gabra H, Marchesi JR, Bennett P, Kyrgiou Met 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

Journal article

Bowden S, Bodinier B, Kalliala I, Zuber V, Vuckovic D, Doulgeraki T, Whitaker M, Wielscher M, Cartwright R, Tsilidis K, Bennett P, Jarvelin M-R, Flanagan J, Chadeau M, Kyrgiou M, FinnGen consortiumet 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

Journal article

Tsonis O, Diakaki K, Gkrozou F, Papadaki A, Dimitriou E, Paraskevaidis M, Kyrgiou M, Paraskevaidis E, Paschopoulos M, Tsapakis EM, Siafaka Vet 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

Journal article

Kechagias KS, Semertzidou A, Athanasiou A, Paraskevaidi M, Kyrgiou Met 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.

Journal article

Semertzidou A, Brosens JJ, McNeish I, Kyrgiou Met al., 2020, Organoid models in gynaecological oncology research, CANCER TREATMENT REVIEWS, Vol: 90, ISSN: 0305-7372

Journal article

Weyers S, Garland SM, Cruickshank M, Kyrgiou M, Arbyn Met al., 2020, Cervical cancer prevention in transgender men: a review, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 128, Pages: 822-826, ISSN: 1470-0328

Journal article

Paraskevaidi M, Cameron SJS, Whelan E, Bowden S, Tzafetas M, Mitra A, Semertzidou A, Athanasiou A, Bennett P, MacIntyre D, Takats Z, Kyrgiou Met 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.

Journal article

Bowden SJ, Lathouras K, Kyrgiou M, 2020, 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

Journal article

Mnimatidis P, Pouliakis A, Valasoulis G, Michail G, Spathis A, Cottaridi C, Margari N, Kyrgiou M, Nasioutziki M, Daponte A, Dinas K, Paraskevaidis E, Panayiotides I, Koutsouris D-Det 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

Journal article

Tzafetas M, Mitra A, Paraskevaidi M, Bodai Z, Kalliala I, Bowden S, Lathouras K, Rosini F, Szasz M, Savage A, Manoli E, Balog J, McKenzie J, Lyons D, Bennett P, MacIntyre D, Ghaem-Maghami S, Takats Z, Kyrgiou Met 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

Journal article

Arbyn M, Gultekin M, Morice P, Nieminen P, Cruickshank M, Poortmans P, Kelly D, Poljak M, Bergeron C, Ritchie D, Schmidt D, Kyrgiou M, Van den Bruel A, Bruni L, Basu P, Bray F, Weiderpass Eet al., 2020, 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

Journal article

Ciavattini A, Carpini GD, Giannella L, Arbyn M, Kyrgiou M, Joura EA, Sehouli J, Carcopino X, Redman CW, Nieminen P, Cruickshank M, Gultekin Met al., 2020, European Federation for Colposcopy (EFC) and European Society of Gynaecological Oncology (ESGO) joint considerations about human papillomavirus (HPV) vaccination, screening programs, colposcopy, and surgery during and after the COVID-19 pandemic, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 30, Pages: 1097-1100, ISSN: 1048-891X

Journal article

Kyrgiou M, Arbyn M, Bergeron C, Bosch FX, Dillner J, Jit M, Kim J, Poljak M, Nieminen P, Sasieni P, Kesic V, Cuzick J, Gultekin Met 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

Journal article

Heinonen A, Jakobsson M, Kiviharju M, Virtanen S, Aro K, Kyrgiou M, Nieminen P, Kalliala Iet al., 2020, Role of Colposcopy after Treatment for Cervical Intraepithelial Neoplasia, CANCERS, Vol: 12

Journal article

Paraskevaidi M, Morais CLM, Ashton KM, Stringfellow HF, McVey RJ, Ryan NAJ, O'Flynn H, Sivalingam VN, Kitson SJ, MacKintosh ML, Derbyshire AE, Pow C, Raglan O, Lima KMG, Kyrgiou M, Martin-Hirsch PL, Martin FL, Crosbie EJet 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.

Journal article

Athanasiou A, Bowden S, Paraskevaidi M, Fotopoulou C, Martin-Hirsch P, Paraskevaidis E, Kyrgiou Met 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.

Journal article

Valasoulis G, Pouliakis A, Michail G, Kottaridi C, Spathis A, Kyrgiou M, Paraskevaidis E, Daponte Aet al., 2020, Alterations of HPV-Related Biomarkers after Prophylactic HPV Vaccination. A Prospective Pilot Observational Study in Greek Women, CANCERS, Vol: 12

Journal article

Paraskevaidis E, Athanasiou A, Paraskevaidi M, Bilirakis E, Galazios G, Kontomanolis E, Dinas K, Loufopoulos A, Nasioutziki M, Kalogiannidis I, Athanasiadis A, Papanikolaou A, Vatopoulou A, Grimbizis G, Tsolakidis D, Daponte A, Valasoulis G, Gritzeli S, Michail G, Adonakis G, Paschopoulos M, Tsonis O, Anaforidou M-E, Batistatou A, Kyrgiou Met 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.

Journal article

Mitra A, MacIntyre D, Ntritsos G, Smith A, Tsilidis K, Marchesi J, Bennett P, moscicki A-B, Kyrgiou Met al., 2020, The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions, Nature Communications, Vol: 11, Pages: 1-13, ISSN: 2041-1723

Emerging evidence suggests associations between the vaginal microbiota (VMB) composition, human papillomavirus (HPV) infection, and cervical intraepithelial neoplasia (CIN); however, causal inference remains uncertain. Here, we use bacterial DNA sequencing from serially collected vaginal samples from a cohort of 87 adolescent and young women aged 16–26 years with histologically confirmed, untreated CIN2 lesions to determine whether VMB composition affects rates of regression over 24 months. We show that women with a Lactobacillus-dominant microbiome at baseline are more likely to have regressive disease at 12 months. Lactobacillus spp. depletion and presence of specific anaerobic taxa including Megasphaera, Prevotella timonensis and Gardnerella vaginalis are associated with CIN2 persistence and slower regression. These findings suggest that VMB composition may be a future useful biomarker in predicting disease outcome and tailoring surveillance, whilst it may offer rational targets for the development of new prevention and treatment strategies.

Journal article

Raglan O, Assi N, Nautiyal J, Lu H, Gabra H, Gunter MJ, Kyrgiou Met al., 2020, Proteomic analysis of malignant and benign endometrium according to obesity and insulin-resistance status using Reverse Phase Protein Array, Publisher: ELSEVIER SCIENCE INC, Pages: 57-72, ISSN: 1931-5244

Conference paper

J Bowden S, Kyrgiou M, 2020, Human papillomavirus, Obstetrics, Gynaecology & Reproductive Medicine, Vol: 30, Pages: 109-118, ISSN: 1751-7214

Human papillomaviruses are ancient small DNA viruses and represent the most common sexually transmitted infection in the world. In the majority, HPV infection is cleared by an incompletely understood immune response. HPV is a necessary but not sufficient cause of cervical cancer, and responsible for a proportion of other anogenital cancers including vulval, vaginal, anal and oropharyngeal. Oncogenesis is likely mediated through viral proteins which hijack host-cell machinery in epithelial keratinocytes and disrupt host tumour-suppressor proteins. Much work has been undertaken to further characterise the natural history of HPV infection and cervical disease. Such efforts have been translated to important public health interventions like the introduction of HPV tests in cervical screening. HPV vaccination programmes are expected to further reduce the incidence of high-risk HPV infections and resultantly HPV-related disease.

Journal article

Tzafetas M, Mitra A, Paraskevaidi M, Bodai Z, Kalliala I, Bowden S, Lathouras K, Rosini F, Szasz M, Savage A, Balog J, McKenzie J, Lyons D, Bennett P, MacIntyre D, Ghaem-Maghami S, Takats Z, Kyrgiou Met 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.

Journal article

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