Imperial College London

Professor Maria Kyrgiou

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Chair in Gynaecologic 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

242 results found

Mitra A, Gultekin M, Bizzarri N, Ellis L, Bowden S, Taumberger N, Bracic T, Vieira-Baptista P, Sehouli J, Kyrgiou Met al., 2023, Genital tract microbiota composition profiles and use of prebiotics and probiotics in gynaecological cancer prevention: review of the current evidence, the European Society of Gynaecological Oncology prevention committee statement, The Lancet Microbe, ISSN: 2666-5247

There is emerging interest in the female genital tract (FGT) microbiota’s role in health and disease. It has been suggested that the FGT microbiota may play a role in the development of gynaecological cancers, which raises the question of whether microbiota manipulation could be a tool for prevention. There is a wealth of data associating HPV infection and subsequent cervical dysplasia with a high-diversity microbiome deplete of Lactobacillus species. Studies of microbiota alterations in endometrial, ovarian, vulval and vaginal malignancies are now emerging and point towards the involvement of similar pathogenic anaerobes. Whilst there are plausible mechanisms through which the microbiota can promote neoplastic transformation, it remains unclear whether the microbiota or the disease are the drivers of those changes. A number of pre-, probiotics and other non-clinician prescribed agents have claimed a therapeutic role in cervical disease. Although some document some benefit, the studies are small, of varying design and high-quality evidence to support their use is lacking. Currently no studies have examined these therapeutics in other gynaecological malignancies. Microbiome manipulation for gynaecological cancer prevention remains a welcome prospect, and warrants larger, well-designed studies. However, at present, there is insufficient evidence to support clinical recommendations that promote their use.

Journal article

McGee AE, Alibegashvili T, Elfgren K, Frey B, Grigore M, Heinonen A, Jach R, Jariene K, Kesic V, Küppers V, Kyrgiou M, Leeson S, Louwers J, Mazurec M, Mergui J, Pedro A, Šavrova A, Siegler E, Tabuica U, Trojnarska D, Trzeszcz M, Turyna R, Volodko N, Cruickshank ME, European Federation for Colposcopy and Pathology of the Lower Genital Tract EFC and the European Society of Gynaecological Oncology ESGOet al., 2023, European consensus statement on expert colposcopy., Eur J Obstet Gynecol Reprod Biol, Vol: 290, Pages: 27-37

BACKGROUND: Following the publication of the European consensus statement on standards for essential colposcopy in 2020, the need for standards relating to more complex and challenging colposcopy practice was recognised. These standards relate to colposcopy undertaken in patients identified through cervical screening and tertiary referrals from colposcopists who undertake standard colposcopy only. This set of recommendations provides a review of the current literature and agreement on care for recognised complex cases. With good uptake of human papillomavirus (HPV) immunisation, we anticipate a marked reduction in cervical disease over the next decade. Still, the expert colposcopist will continue to be vital in managing complex cases, including previous cervical intraepithelial neoplasia (CIN)/complex screening histories and multi-zonal disease. AIMS: To provide expert guidance on complex colposcopy cases through published evidence and expert consensus. MATERIAL & METHODS: Members of the EFC and ESGO formed a working group to identify topics considered to be the remit of the expert rather than the standard colposcopy service. These were presented at the EFC satellite meeting, Helsinki 2021, for broader discussion and finalisation of the topics. RESULTS & DISCUSSION: The agreed standards included colposcopy in pregnancy and post-menopause, investigation and management of glandular abnormalities, persistent high-risk HPV+ with normal/low-grade cytology, colposcopy management of type 3 transformation zones (TZ), high-grade cytology and normal colposcopy, colposcopy adjuncts, follow-up after treatment with CIN next to TZ margins and follow-up after treatment with CIN with persistent HPV+, and more. These standards are under review to create a final paper of consensus standards for dissemination to all EFC and ESGO members.

Journal article

Garg A, Ellis L, Love R, Grewal K, Bowden S, Bennett P, Kyrgiou Met al., 2023, Vaginal microbiome in obesity and its impact on reproduction, Best Practice and Research: Clinical Obstetrics and Gynaecology, Vol: 90, Pages: 1-20, ISSN: 1521-6934

A number of reproductive outcomes have been increasingly found to be affected by thevaginal microbiota. Obesity has become a global epidemic, has been affectingincreasing numbers of reproductive-age women, and has been shown to be a riskfactor for a number of adverse female health outcomes. A healthy vaginal microbiomeis characterised by Lactobacillus-dominance, in particular Lactobacillus crispatus;obesity has been found to be associated with higher diversity and a lower likelihood ofLactobacillus-dominance. In this review, we summarise the evidence on the vaginalmicrobiome in obese women and the impact on reproductive outcomes such asconception rates, early pregnancy and preterm birth. We further explore themechanisms by which obesity may result in an altered microbial composition, andhighlight future avenues for therapeutic targeting of the vaginal microbiota.

Journal article

Bowden SJ, Doulgeraki T, Bouras E, Markozannes G, Athanasiou A, Grout-Smith H, Kechagias KS, Ellis LB, Zuber V, Chadeau-Hyam M, Flanagan JM, Tsilidis KK, Kalliala I, Kyrgiou Met al., 2023, Risk factors for human papillomavirus infection, cervical intraepithelial neoplasia and cervical cancer: an umbrella review and follow-up Mendelian randomisation studies, BMC Medicine, Vol: 21, Pages: 1-15, ISSN: 1741-7015

Background: Persistent infection by oncogenic human papillomavirus (HPV) is necessary although not sufficient for development of cervical cancer. Behavioural, environmental, or comorbid exposures may promote or protect against malignant transformation. Randomised evidence is limited and the validity of observational studies describing these associations remains unclear.Methods: In this umbrella review we searched electronic databases to identify meta-analyses of observational studies that evaluated risk or protective factors and the incidence of HPV infection, cervical intra-epithelial neoplasia (CIN), cervical cancer incidence and mortality. Following re-analysis, evidence was classified and graded based on a pre-defined set of statistical criteria. Quality was assessed with AMSTAR-2. For all associations graded as weak evidence or above, with available genetic instruments, we also performed Mendelian randomisation to examine the potential causal effect of modifiable exposures with risk of cervical cancer. The protocol for this study was registered on PROSPERO (CRD42020189995).Results: We included 171 meta-analyses of different exposure contrasts from 50 studies. Systemic immunosuppression including HIV infection (RR=2.20(95%CI=1.89-2.54)) and immunosuppressive medications for inflammatory bowel disease (RR=1.33(95%CI=1.27-1.39)), as well as an altered vaginal microbiome (RR=1.59(95%CI=1.40-1.81)) were supported by strong and highly suggestive evidence for an association with HPV persistence, CIN or cervical cancer. Smoking, number of sexual partners and young age at first pregnancy were supported by highly suggestive evidence and confirmed by Mendelian randomisation.Conclusions: Our main analysis supported the association of systemic (HIV infection, immunosuppressive medications) and local immunosuppression (altered vaginal microbiota) with increased risk for worse HPV and cervical disease outcomes. Mendelian randomisation confirmed the link for genetically predic

Journal article

Ellis L, Jones B, Yagel I, Walker-Jacobs A, Galani A, Hamlyn L, Kyrgiou Met al., 2023, Uterine sarcoma: Almost more tumor than patient, Archives of Gynecology and Obstetrics, ISSN: 0932-0067

Journal article

Bowden SJ, Ellis L, Kalliala I, Paraskevaidi M, Tighe J, Kechagias K, Doulgeraki T, Paraskevaidis E, Arbyn M, Flanagan J, Veroniki AA, Kyrgiou Met 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, Vol: 13, Pages: 1-8, ISSN: 2044-6055

Introduction Human papillomavirus (HPV) is necessary but not sufficient for cervical cancer development. During cervical carcinogenesis, methylation levels increase across host and HPV DNA. DNA methylation has been proposed as a test to diagnose cervical intraepithelial neoplasia (CIN); we present a protocol to evaluate the accuracy of methylation markers to detect high-grade CIN and cervical cancer.Methods and analysis We will search electronic databases (Medline, Embase and Cochrane Library), from inception, to identify studies examining DNA methylation as a diagnostic marker for CIN or cervical cancer, in a cervical screening population. The primary outcome will be to assess the diagnostic test accuracy of host and HPV DNA methylation for high-grade CIN; the secondary outcomes will be to examine the accuracy of different methylation cut-off thresholds, and accuracy in high-risk HPV positive women. Our reference standard will be histology. We will perform meta-analyses using Cochrane guidelines for diagnostic test accuracy. We will use the number of true positives, false negatives, true negatives and false positives from individual studies. We will use the bivariate mixed effect model to estimate sensitivity and specificity with 95% CIs; we will employ different bivariate models to estimate sensitivity and specificity at different thresholds if sufficient data per threshold. For insufficient data, the hierarchical summary receiver operating curve model will be used to calculate a summary curve across thresholds. If there is interstudy and intrastudy variation in thresholds, we will use a linear mixed effects model to calculate the optimum threshold. If few studies are available, we will simplify models by assuming no correlation between sensitivity and specificity and perform univariate, random-effects meta-analysis. We will assess the quality of studies using QUADAS-2 and QUADAS-C.Ethics and dissemination Ethical approval is not required. Results will be dissemin

Journal article

Semertzidou A, Grout-Smith H, Kalliala I, Garg A, Terzidou V, Marchesi J, MacIntyre D, Bennett P, Tsilidis K, Kyrgiou Met al., 2023, Diabetes and anti-diabetic interventions and the risk of gynaecological and obstetric morbidity: an umbrella review of the literature, BMC Medicine, Vol: 21, Pages: 1-15, ISSN: 1741-7015

BackgroundDiabetes has reached epidemic proportions in recent years with serious health ramifications. The aim of this study was to evaluate the strength and validity of associations between diabetes and anti-diabetic interventions and the risk of any type of gynaecological or obstetric conditions.MethodsDesign: Umbrella review of systematic reviews and meta-analyses.Data sources: PubMed, Medline, Embase, Cochrane Database of Systematic Reviews, manual screening of references.Eligibility criteria: Systematic reviews and meta-analyses of observational and interventional studies investigating the relationship between diabetes and anti-diabetic interventions with gynaecological or obstetric outcomes. Meta-analyses that did not include complete data from individual studies, such as relative risk, 95% confidence intervals, number of cases/controls, or total population were excluded.Data analysis: The evidence from meta-analyses of observational studies was graded as strong, highly suggestive, suggestive or weak according to criteria comprising the random effects estimate of meta-analyses and their largest study, the number of cases, 95% prediction intervals, I2 heterogeneity index between studies, excess significance bias, small study effect and sensitivity analysis using credibility ceilings. Interventional meta-analyses of randomised controlled trials were assessed separately based on the statistical significance of reported associations, the risk of bias and quality of evidence (GRADE) of included meta-analyses.ResultsA total of 117 meta-analyses of observational cohort studies and 200 meta-analyses of randomised clinical trials that evaluated 317 outcomes were included. Strong or highly suggestive evidence only supported a positive association between gestational diabetes and caesarean section, large for gestational age babies, major congenital malformations and heart defects and an inverse relationship between metformin use and ovarian cancer incidence. Only a fifth

Journal article

Kesic V, Carcopino X, Preti M, Vieira-Baptista P, Bevilacqua F, Bornstein J, Chargari C, Cruickshank M, Erzeneoglu E, Gallio N, Gultekin M, Heller D, Joura E, Kyrgiou M, Madic T, Planchamp F, Regauer S, Reich O, Esat Temiz B, Woelber L, Zodzika J, Stockdale Cet al., 2023, The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) Consensus Statement on the Management of Vaginal Intraepithelial Neoplasia, JOURNAL OF LOWER GENITAL TRACT DISEASE, Vol: 27, Pages: 131-145, ISSN: 1089-2591

Journal article

Kamani MO, Kyrgiou M, Joura E, Zapardiel I, Grigore M, Arbyn M, Preti M, Planchamp F, Gultekin Met al., 2023, ESGO Prevention Committee opinion: is a single dose of HPV vaccine good enough?, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 33, Pages: 462-464, ISSN: 1048-891X

Journal article

Hughes KC, Herring TA, Song JN, Gately RV, Przybyl LM, Ogilvie RP, Simon K, Bhuyan PK, Kyrgiou M, Seeger JDet al., 2023, Cervical High-Grade Squamous Intraepithelial Lesion Burden and Standard of Care Treatment Effectiveness and Safety in the United States, 2008-2018: The EACH-WOMAN Project, JOURNAL OF LOWER GENITAL TRACT DISEASE, Vol: 27, Pages: 105-112, ISSN: 1089-2591

Journal article

Kesic V, Carcopino X, Preti M, Vieira-Baptista P, Bevilacqua F, Bornstein J, Chargari C, Cruickshank M, Erzeneoglu E, Gallio N, Gultekin M, Heller D, Joura E, Kyrgiou M, Madic T, Planchamp F, Regauer S, Reich O, Esat Temiz B, Woelber L, Zodzika J, Stockdale Cet al., 2023, The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) consensus statement on the management of vaginal intraepithelial neoplasia, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 33, Pages: 446-461, ISSN: 1048-891X

Journal article

Kechagias KS, Zafeiri M, Triantafyllidis KK, Kyrtsonis G, Geropoulos G, Lyons D, Burney Ellis L, Bowden S, Galani A, Paraskevaidi M, Kyrgiou Met al., 2023, Primary Melanoma of the Cervix Uteri: A Systematic Review and Meta-Analysis of the Reported Cases, BIOLOGY-BASEL, Vol: 12

Journal article

Giannos P, Kechagias K, Paraskevaidi M, Kyrgiou Met 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

Journal article

Dinoi G, Ghoniem K, Murad MH, Segarra-Vidal B, Zanfagnin V, Coronado PJ, Kyrgiou M, Perrone AM, Zola P, Weaver A, McGree M, Fanfani F, Scambia G, Ramirez PT, Mariani Aet al., 2023, Minimally invasive compared with open surgery in high-risk endometrial cancer a systematic review and meta-analysis, Obstetrics and Gynecology, Vol: 141, Pages: 59-68, ISSN: 0029-7844

OBJECTIVE: To compare outcomes between minimally invasive surgery and open surgery in patients with high-risk endometrial cancer.DATA SOURCES: A cohort study of all patients who underwent surgery for high-risk endometrial cancer between 1999 and 2016 at Mayo Clinic (Rochester, Minnesota) and a literature search of MEDLINE, EMBASE, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, and Scopus of all published studies until December 2020.METHODS OF STUDY SELECTION: The systematic review identified 2,332 patients (14 studies, all retrospective except a subanalysis of a randomized comparison) and the cohort study identified 542 additional patients. Articles were included if reporting original data on overall survival and disease-free survival among patients with high-risk endometrial cancer, defined as International Federation of Gynecology and Obstetrics grade 3 endometrioid, serous, clear cell, mixed histology, or uterine carcinosarcoma. Studies that did not report at least one of the main outcomes, those in which one surgical technique (robotic or laparoscopic surgery) was missing in the comparison analysis with open surgery, and case reports were excluded. Additional data were extracted from a retrospective cohort of patients from Mayo. A random-effect model was used for meta-analysis.TABULATION, INTEGRATION, AND RESULTS: This systematic review and meta-analysis was registered in PROSPERO. Literature search and data extraction were performed independently by two reviewers, as well as quality assessment using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology, and the Newcastle-Ottawa Scale. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. Meta-analysis showed that disease-free survival and overall survival in patients with high-risk endometrial cancer who underwent minimally invasive surgery were not statistically different from those of patients who underwent op

Journal article

Mitra A, Verbakel JY, Kasaven LS, Tzafetas M, Grewal K, Jones B, Bennett PR, Kyrgiou M, Saso Set al., 2023, The menstrual cycle and the COVID-19 pandemic., PLoS One, Vol: 18

BACKGROUND: The impact of COVID-19 virus on menstrual cycles in unvaccinated women is limited. OBJECTIVE: To investigate the prevalence of changes to menstrual cycle characteristics, hormonal symptoms and lifestyle changes prior to and during the COVID-19 pandemic. METHODS: A retrospective online cross-sectional survey completed by social media users between July 2020 to October 2020. Participants were living in the United Kingdom (UK), premenopausal status and, or over 18 years of age. MAIN OUTCOME(S) AND MEASURES(S): The primary outcome was to assess changes to menstrual cycle characteristics during the pandemic following the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). Secondary outcomes included assessment of hormonal and lifestyle changes. RESULTS: 15,611 social media users completed the survey. Of which, 75% of participants experienced a change in their menstrual cycle, with significantly greater proportions reporting irregular menstrual cycles (P<0·001), bleeding duration more than seven days (P<0·001), longer mean cycle length (P<0·001) and overall bleeding duration (P<0·001). Over half the participants reported worsening of premenstrual symptoms including low mood/depression, anxiety and irritability. When stratified according to COVID-19 infection, there was no significant difference in menstrual cycle changes. CONCLUSION: The COVID-19 pandemic resulted in considerable variation in menstrual cycle characteristics and hormonal symptoms. This appears to be related to societal and lifestyle changes resulting from the pandemic, rather than to the virus itself. We believe this may have an impact on the individual, as well as national economy, healthcare, and population levels, and therefore suggest this should be taken into consideration by governments, healthcare providers and employers when developing pandemic recovery plans.

Journal article

Kechagias K, Katsikas-Triantafyllidis K, Geropoulos G, Giannos P, Zafeiri M, Tariq-Mian I, Paraskevaidi M, Mitra A, Kyrgiou Met 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

Journal article

Kyrgiou M, Moscicki A-B, 2022, Vaginal microbiome and cervical cancer, SEMINARS IN CANCER BIOLOGY, Vol: 86, Pages: 189-198, ISSN: 1044-579X

Journal article

Kiviharju M, Heinonen A, Jakobsson M, Virtanen S, Auvinen E, Kotaniemi-Talonen L, Dillner J, Kyrgiou M, Nieminen P, Aro K, Kalliala Iet al., 2022, Overtreatment rate after immediate local excision of suspected cervical intraepithelial neoplasia: A prospective cohort study, GYNECOLOGIC ONCOLOGY, Vol: 167, Pages: 167-173, ISSN: 0090-8258

Journal article

Semertzidou A, Whelan E, Smith A, Ng S, Brosens J, Marchesi J, Bennett P, MacIntyre D, Kyrgiou Met al., 2022, Microbial signatures and continuum in endometrial cancer and benign patients

<jats:title>Abstract</jats:title> <jats:p>Endometrial cancer is a multifactorial disease with inflammatory, metabolic and potentially microbial cues involved in disease pathogenesis. Here we sampled different regions of the reproductive tract (vagina, cervix, endometrium, fallopian tubes and ovaries) of 61 patients and showed that the upper genital tract of a subset of women with and without endometrial cancer harbour microbiota quantitatively and compositionally distinguishable from background contaminants. A microbial continuum, defined by detection of common bacterial species along the genital tract, was noted in most women without cancer while the continuum was less cohesive in endometrial cancer patients. Vaginal microbiota were poorly correlated with rectal microbiota in the studied cohorts. Endometrial cancer was associated with reduced cervicovaginal and rectal bacterial load together with depletion of <jats:italic>Lactobacillus</jats:italic> species relative abundance, including <jats:italic>L. crispatus</jats:italic>, increased bacterial diversity and enrichment of <jats:italic>Porphyromonas</jats:italic>, <jats:italic>Prevotella, Peptoniphilus</jats:italic> and <jats:italic>Anaerococcus</jats:italic> in the lower genital tract and endometrium. Treatment of benign and malignant endometrial organoids with <jats:italic>L. crispatus</jats:italic> conditioned media had minimal impact on cytokine and chemokine profiles. Our findings provide evidence that the upper female reproductive tract of some women contains detectable levels of bacteria, the composition of which is associated with endometrial cancer. Whether this is a cause or consequence of cancer pathophysiology remains to be elucidated.</jats:p>

Journal article

Bowden S, Ellis L, Kyrgiou M, Fiander AN, Hibbitts Set al., 2022, High prevalence of HPV 51 in an unvaccinated population and implications for HPV vaccines, Vaccines, Vol: 10, ISSN: 2076-393X

Human papillomavirus (HPV) is detected in 99.7% of cervical cancers. Current vaccines target types 16 and 18. Prior to vaccination implementation, a prospective cohort study was conducted to determine baseline HPV prevalence in unvaccinated women in Wales; after HPV16 and HPV18, HPV 51 was found to be most prevalent. This study aimed to re-assess the unexpected high prevalence of HPV 51 and consider its potential for type-replacement. Two hundred HPV 51 positive samples underwent re-analysis by repeating the original methodology using HPV 51 GP5+/6+ PCR-enzyme immunoassay, and additionally a novel assay of HPV 51 E7 PCR. Data were correlated with age, social deprivation and cytology. Direct repeat of HPV 51 PCR-EIA identified 146/195 (75.0%) samples as HPV 51 positive; E7 PCR identified 166/195 (85.1%) samples as HPV 51 positive. HPV 51 prevalence increased with cytological grade. The prevalence of HPV 51 in the pre-vaccinated population was truly high. E7 DNA assays may offer increased specificity for HPV genotyping. Cross-protection of current vaccines against less-prevalent HPV types warrants further study. This study highlights the need for longitudinal investigation into the prevalence of non-vaccine HPV types, especially those phylogenetically different to vaccine types for potential type-replacement. Ongoing surveillance will inform future vaccines.

Journal article

Taumberger N, Joura EA, Arbyn M, Kyrgiou M, Sehouli J, Gultekin Met al., 2022, Myths and fake messages about human papillomavirus (HPV) vaccination: answers from the ESGO Prevention Committee, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 32, Pages: 1316-1320, ISSN: 1048-891X

Journal article

Kechagias K, Kalliala I, Bowden S, Athanasiou A, Paraskevaidi M, Veroniki A, Kyrgiou Met 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

Journal article

Kyrgiou M, Athanasiou A, Arbyn M, Lax S, Raspollini MR, Nieminen P, Carcopino X, Bornstein J, Gultekin M, Paraskevaidis Eet al., 2022, Terminology for dimensions of cone after local conservative treatment for cervical intra-epithelial neoplasia and early invasive cervical cancer: 2022 consensus recommendations from ESGO, EFC, IFCPC, and ESP, The Lancet Oncology, Vol: 23, Pages: e385-e392, ISSN: 1213-9432

Local cervical treatment for squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN) removes or ablates a cone-shaped or dome-shaped part of the cervix that contains abnormal cells. This Series paper introduces the 2022 terminology for cone dimensions after local conservative treatment for SIL, CIN, or early invasive cervical cancer. The terminology was prepared by the Nomenclature Committee of the European Society of Gynaecologic Oncology, the European Federation for Colposcopy, the International Federation of Cervical Pathology and Colposcopy, and the European Society of Pathology. Cone length should be tailored to the type of transformation zone. Treatment of SIL or CIN is associated with an increased risk of preterm birth, which escalates with increasing cone length. There is a lack of agreement regarding terms used to report excised specimen dimensions both intraoperatively and in the pathology laboratory. Consensus is needed to make studies addressing effectiveness and safety of SIL or CIN treatment comparable, and to facilitate their use to improve accuracy of antenatal surveillance and management. This Series paper summarises the current terminology through a review of existing literature, describes new terminology as agreed by a group of experts from international societies in the field of cervical cancer prevention and treatment, and recommends use of the new terminology that will facilitate communication between clinicians and foster more specific treatment guidelines that balance obstetrical harm against therapeutic effectiveness.

Journal article

Kyrgiou M, Athanasiou A, Arbyn M, Lax SF, Raspollini MR, Nieminen P, Carcopino X, Bornstein J, Gultekin M, Paraskevaidis Eet al., 2022, Terminology for cone dimensions after local conservative treatment for cervical intraepithelial neoplasia and early invasive cervical cancer: 2022 consensus recommendations from ESGO, EFC, IFCPC, and ESP, The Lancet Oncology, Vol: 23, Pages: e385-e392, ISSN: 1470-2045

Local cervical treatment for squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN) removes or ablates a cone-shaped or dome-shaped part of the cervix that contains abnormal cells. This Series paper introduces the 2022 terminology for cone dimensions after local conservative treatment for SIL, CIN, or early invasive cervical cancer. The terminology was prepared by the Nomenclature Committee of the European Society of Gynaecologic Oncology, the European Federation for Colposcopy, the International Federation of Cervical Pathology and Colposcopy, and the European Society of Pathology. Cone length should be tailored to the type of transformation zone. Treatment of SIL or CIN is associated with an increased risk of preterm birth, which escalates with increasing cone length. There is a lack of agreement regarding terms used to report excised specimen dimensions both intraoperatively and in the pathology laboratory. Consensus is needed to make studies addressing effectiveness and safety of SIL or CIN treatment comparable, and to facilitate their use to improve accuracy of antenatal surveillance and management. This Series paper summarises the current terminology through a review of existing literature, describes new terminology as agreed by a group of experts from international societies in the field of cervical cancer prevention and treatment, and recommends use of the new terminology that will facilitate communication between clinicians and foster more specific treatment guidelines that balance obstetrical harm against therapeutic effectiveness.

Journal article

Athanasiou A, Veroniki AA, Efthimiou O, Kalliala I, Naci H, Bowden S, Paraskevaidi M, Arbyn M, Lyons D, Martin-Hirsch P, Bennett P, Paraskevaidis E, Salanti G, Kyrgiou Met 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

Journal article

Salamalekis E, Pouliakis A, Margari N, Kottaridi C, Spathis A, Karakitsou E, Gouloumi AR, Leventakou D, Chrelias G, Valasoulis G, Nasioutziki M, Kyrgiou M, Dinas K, Panayiotides IG, Paraskevaidis E, Chrelias Cet al., 2022, An artificial intelligence approach for the detection of cervical abnormalities: Application of the self organizing map, Research Anthology on Medical Informatics in Breast and Cervical Cancer, Pages: 267-288, ISBN: 9781668471364

Numerous ancillary techniques detecting HPV DNA or mRNA are viewed as competitors or ancillary techniques to test Papanicolaou. However, no technique is perfect because sensitivity increases at the cost of specificity. Various methods have been applied to resolve this issue by using many examination results, such as classification and regression trees and supervised artificial neural networks. In this article, 1258 cases with results from test Pap, HPV DNA, HPV mRNA, and p16 were used to evaluate the performance of the self-organizing map (SOM). An artificial neural network has three advantages: it is unsupervised, can tolerate missing data, and produces topographical maps. The results of the SOM application were encouraging and produced maps depicting the important tests.

Book chapter

Valasoulis G, Michail G, Pouliakis A, Androutsopoulos G, Panayiotides IG, Kyrgiou M, Daponte A, Paraskevaidis Eet al., 2022, Effect of Condom Use after CIN Treatment on Cervical HPV Biomarkers Positivity: Prolonged Follow Up Study, CANCERS, Vol: 14

Journal article

Henschke N, Bergman H, Villanueva G, Loke YK, Golder SP, Crosbie EJ, Kyrgiou M, Dwan K, Morrison Jet al., 2022, Effects of human papillomavirus (HPV) vaccination programmes on community rates of HPV-related disease and harms from vaccination, Cochrane Database of Systematic Reviews, Vol: 2022, ISSN: 1465-1858

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. We aim to assess population-level effects of human papillomavirus (HPV) vaccination programmes on HPV-related disease and harms from vaccination.

Journal article

Bergman H, Henschke N, Villanueva G, Loke YK, Golder SP, Dwan K, Crosbie EJ, Kyrgiou M, Platt J, Morrison Jet al., 2022, Human papillomavirus (HPV) vaccination for the prevention of cervical cancer and other HPV-related diseases: a network meta-analysis, Cochrane Database of Systematic Reviews, Vol: 2022, ISSN: 1465-1858

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. We aim to evaluate the safety and efficacy of WHO pre-qualified human papillomavirus (HPV) vaccines given in different dose schedules, in females and males, to prevent cervical cancer and other HPV-related diseases by undertaking a network meta-analysis (NMA). We will rank the different vaccines and dose schedules according to the critical outcomes.

Journal article

Whelan E, Kalliala I, Semertzidou A, Raglan O, Bowden S, Kechagias K, Markozannes G, Cividini S, McNeish I, Marchesi J, MacIntyre D, Bennett P, Tsilidis K, Kyrgiou Met 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>

Journal article

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