Imperial College London

DrAnitaMitra

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Clinical Lecturer
 
 
 
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a.mitra

 
 
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Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

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58 results found

Mitra A, Gultekin M, Bizzarri N, Ellis L, Bowden S, Taumberger N, Bracic T, Vieira-Baptista P, Sehouli J, Kyrgiou Met al., 2024, 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, Vol: 5, Pages: E291-E300, 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

Kasaven LS, Mitra A, Ostrysz P, Theodorou E, Murugesu S, Yazbek J, Bracewell-Milnes T, Ben Nagi J, Jones BP, Saso Set al., 2023, Exploring the knowledge, attitudes, and perceptions of women of reproductive age towards fertility and elective oocyte cryopreservation for age-related fertility decline in the UK: a cross-sectional survey., Hum Reprod, Vol: 38, Pages: 2478-2488

STUDY QUESTION: What are the knowledge, perceptions and attitudes towards fertility and elective oocyte cryopreservation (OC) for age-related fertility decline (ARFD) in women in the UK? SUMMARY ANSWER: Awareness of OC for ARFD has reportedly improved compared to studies carried out almost a decade ago, but inconsistencies in knowledge remain regarding the rate of miscarriage amongst specific age groups, the financial costs and optimal age to undergo OC for ARFD. WHAT IS KNOWN ALREADY: The age of first-time motherhood has increased amongst western societies, with many women of reproductive age underestimating the impact of age on fertility. Further understanding of women's awareness of their fertility, the options available to preserve it and the barriers for seeking treatment earlier are required in order to prevent the risk of involuntary childlessness. STUDY DESIGN, SIZE, DURATION: A hyperlink to a cross-sectional survey was posted on social media (Instagram) between 25 February 2021 and 11 March 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women from the general population aged 18-50 years were invited to complete the survey. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 5482 women fulfilled the inclusion criteria and completed the survey. The mean age of participants was 35.0 years (SD 10.25; range 16-52). Three quarters (74.1%; n = 4055) disagreed or strongly disagreed they felt well informed regarding the options available to preserve their fertility, in case of a health-related problem or ARFD. The majority overestimated the risk of miscarriage in women aged ≥30 years old, with 14.5% correctly answering 20%, but underestimated the risks in women ≥40, as 20.1% correctly answered 40-50%. Three quarters (73.2%; n = 4007) reported an awareness of OC for ARFD and 65.8% (n = 3605) reported that they would consider undergoing the procedure. The number of women who considered OC for ARFD across

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

L'Heveder A, Chan M, Mitra A, Kasaven L, Saso S, Prior T, Pollock N, Dooley M, Joash K, Jones BPet al., 2022, Sports Obstetrics: Implications of Pregnancy in Elite Sportswomen, a Narrative Review, JOURNAL OF CLINICAL MEDICINE, Vol: 11

Journal article

Kasaven L, Jones B, L'Heveder A, Chan M, Mitra A, Saso S, Joash K, Dooley M, Tomas P, Pollock Net al., 2022, Implications of pregnancy in elite sportswomen, Journal of Clinical Medicine, ISSN: 2077-0383

Increasing numbers of females are participating in elite sport, with a record number having competed at the Tokyo Olympic Games. Importantly, the ages of peak performance and fertility are very likely to coincide, as such, it is inevitable that pregnancy will occur during training andcompetition. Whilst there is considerable evidence to promote regular exercise in pregnancy, withbenefits including a reduction in hypertensive disorders, gestational diabetes and reduced rates ofpost-natal depression, few studies have been conducted which include elite athletes. Indeed, thereare concerns that high-intensity exercise may lead to increased rates of miscarriage and pretermlabour amongst other pregnancy-related complications. There is minimal guidance on the obstetricmanagement of athletes and consequently healthcare professionals frequently adopt a very conservative approach to managing such people. This narrative review summarises the evidence onthe antenatal, intrapartum and postpartum outcomes in elite athletes and provides recommendations for healthcare providers demonstrating that generally, pregnant athletes can continue theirtraining, with a few notable exceptions. It also summarises the physiological changes that occur inpregnancy and reviews the literature base regarding how these changes may impact performance,with benefits arising from pregnancy-associated cardiovascular adaptations at earlier gestations,but later changes causing increased risk of injury and fatigue.

Journal article

Mitra A, MacIntyre DA, Paraskevaidi M, Moscicki A-B, Mahajan V, Smith A, Lee YS, Lyons D, Paraskevaidis E, Marchesi JR, Bennett PR, Kyrgiou Met 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

Journal article

Bowden S, Bodinier B, Paraskevaidi M, Kalliala I, Chaitrakulthong N, Mitra A, Tzafetas M, Lathouras K, Nasioutziki M, Flanagan J, Chadeau-Hyam M, Kyrgiou Met 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

Conference paper

Mitra A, 2021, Blood clots, covid vaccines & the contraceptive pill: are we heading for a repeat of the 1995 pill scare?, BMJ Sexual & Reproductive Health, Vol: 47, Pages: 303-304, ISSN: 2515-1991

Journal article

Mitra A, MacIntyre D, Paraskevaidi M, Moscicki A-B, Mahajan V, Smith A, Lyons D, Paraskevaidis E, Marchesi J, Bennett P, Kyrgiou Met 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

Working 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

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

Tahmasebi F, Stewart S, Mitra A, Morje M, Sayasneh Aet al., 2020, Transvaginal saline contrast sonohystography to investigate postmenopausal bleeding: a systematic review, Cureus, Vol: 12, Pages: 1-14, ISSN: 2168-8184

Transvaginal ultrasound (TVUS) is the initial investigation of choice for postmenopausal bleeding (PMB), followed by diagnostic hysteroscopy and endometrial sampling if abnormalities are detected. Saline contrast sonohysterography (SCSH) - injection of saline through the cervix into the uterine cavity prior to TVUS - allowed increased diagnostic accuracy in women with PMB in several small, heterogeneous studies.The objectives of the current study were to evaluate the diagnostic accuracy of SCSH in women with PMB, comparing findings with surgical and pathological reports, highlight the necessity of SCSH in guiding clinical decision-making, and establish if there is an increase/decrease in the number of hysteroscopies performed for PMB and, hence, the adherence of clinicians to imaging referral guidelines.The search strategy included formulating search terms identifying all synonyms of SCSH and postmenopause. The databases searched were MEDLINE, Embase, and the Cochrane Library.Only studies comparing SCSH to an alternative method were selected. The studies were screened and data analysis performed using content analysis. Data reduction was performed through systematic coding and the generation of themesWe identified 18 studies, comprising 974 women, using SCSH to evaluate the endometrial cavity in women with PMB; most support SCSH improving diagnostic accuracy through delineating intracavitary structures.In effect, SCSH could be a first-line investigative modality to assess the uterine cavity once a larger, well-designed study has been conducted to clarify its specificity, sensitivity, and positive predictive value (PPV). Owing to its relatively non-invasive nature and potentially high diagnostic accuracy, SCSH could allow for more accurate decisions regarding the need for further investigation and subsequent management.

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

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

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

Bowden SJ, Kalliala I, Veroniki AA, Arbyn M, Mitra A, Lathouras K, Mirabello L, Chadeau-Hyam M, Paraskevaidis E, Flanagan JM, Kyrgiou Met al., 2019, The use of Human Papillomavirus DNA Methylation in cervical intraepithelial neoplasia: a systematic review and meta-analysis, EBioMedicine, Vol: 50, Pages: 246-259, ISSN: 2352-3964

BackgroundMethylation of viral DNA has been proposed as a novel biomarker for triage of human papillomavirus(HPV) positive women at screening. This systematic review and meta-analysis aims to assess how methylation levels change with disease severity and to determine diagnostic test accuracy (DTA) in detectinghigh-grade cervical intra-epithelial neoplasia (CIN).MethodsWe performed searches in MEDLINE, EMBASE and CENTRAL from inception to October 2019. Studies were eligible if they explored HPV methylation levels in HPV positive women. Data were extracted induplicate and requested from authors where necessary. Random-effects models and a bivariate mixed-effectsbinary regression model were applied to determine pooled effect estimates.Findings44 studies with 8819 high-risk HPV positive women were eligible. The pooled estimates for positive methylation rate in HPV16 L1 gene were higher for high-grade CIN (≥CIN2/high-grade squamousintra-epithelial lesion (HSIL) (95% confidence interval (95%CI:72·7% (47·8–92·2))) vs. low-grade CIN(≤CIN1/low-grade squamous intra-epithelial lesion (LSIL) (44·4% (95%CI:16·0–74·1))). Pooled differencein mean methylation level was significantly higher in ≥CIN2/HSIL vs. ≤CIN1/LSIL for HPV16 L1 (11·3%(95%CI:6·5–16·1)). Pooled odds ratio of HPV16 L1 methylation was 5·5 (95%CI:3·5–8·5) for ≥CIN2/HSIL vs. ≤CIN1/LSIL (p < 0·0001). HPV16 L1/L2 genes performed best in predicting CIN2 or worse(pooled sensitivity 77% (95%CI:63–87), specificity 64% (95%CI:55–71), area under the curve (0·73(95%CI:0·69–0·77)).InterpretationHigher HPV methylation is associated with increased disease severity, whilst HPV16 L1/L2 genes demonstrated high diagnostic accuracy to detect high-grade CIN in HPV16 positive women. Direct clinical use islimited by the need for a multi-genotype and standardised ass

Journal article

Tzafetas M, Mitra A, Kalliala I, Lever S, Bodai Z, Rosini F, Savage A, McKenzie J, MacIntyre D, Ghaem-Maghami S, Takats Z, Kyrgiou Met al., 2019, THE IKNIFE AND ITS APPLICATION FOR THE TREATMENT OF CERVICAL ABNORMALITIES, Publisher: BMJ PUBLISHING GROUP, Pages: A589-A589, ISSN: 1048-891X

Conference paper

Bowden S, Kalliala I, Veroniki A, Arbyn M, Mitra A, Lathouras K, Mirabello L, Chadeau-Hyam M, Paraskevaidis E, Flanagan J, Kyrgiou Met al., 2019, THE USE OF HUMAN PAPILLOMAVIRUS DNA METHYLATION IN CERVICAL INTRAEPITHELIAL NEOPLASIA: A SYSTEMATIC REVIEW AND META-ANALYSIS, Publisher: BMJ PUBLISHING GROUP, Pages: A84-A86, ISSN: 1048-891X

Conference paper

Tzafetas M, Mitra A, Lever S, Kalliala I, MacIntyre D, Ghaem-Maghami S, Kyrgiou Met al., 2019, ONCOLOGICAL AND REPRODUCTIVE OUTCOMES AFTER FERTILITY-SPARING SURGERY IN WOMEN WITH CERVICAL CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS, Publisher: BMJ PUBLISHING GROUP, Pages: A76-A77, ISSN: 1048-891X

Conference paper

Mitra A, Macintyre D, Lee Y, Smith A, Marchesi J, Lyons D, Stock S, Bennett P, Kyrgiou Met al., 2019, CERVICAL INTRAEPITHELIAL NEOPLASIA IS ASSOCIATED WITH AN ALTERED VAGINAL MICROBIOME AND INNATE IMMUNE DISRUPTION, Publisher: BMJ PUBLISHING GROUP, Pages: A71-A71, ISSN: 1048-891X

Conference paper

Mitra A, Macintyre D, Ntritsos G, Smith A, Tsilidis K, Marchesi J, Bennett P, Moscicki A-B, Kyrgiou Met al., 2019, THE ROLE OF THE VAGINAL MICROBIOTA IN THE REGRESSION OF UNTREATED CIN2 LESIONS, Publisher: BMJ PUBLISHING GROUP, Pages: A37-A37, ISSN: 1048-891X

Conference paper

Wiik J, Sengpiel V, Kyrgiou M, Nilsson S, Mitra A, Tanbo T, Jonassen CM, Tannæs TM, Sjøborg Ket al., 2019, Cervical microbiota in women with cervical intra-epithelial neoplasia, prior to and after local excisional treatment, a Norwegian cohort study, BMC Women's Health, Vol: 19, ISSN: 1472-6874

BackgroundLocal treatment for cervical intraepithelial neoplasia (CIN) by Loop Electrosurgical Excision Procedure (LEEP) has been correlated with reproductive morbidity, while the cervicovaginal microbiota is also known to affect the risk of preterm delivery. CIN and treatment by LEEP might change the cervical microbiota. The main aim of this study was to describe the cervical microbiota before and after LEEP and assess its associaton with cone depth and HPV persistence. Further, we aimed to compare the microbiota to references with normal cervical cytology.MethodsBetween 2005 and 2007, we prospectively identified 89 women planned for LEEP in a Norwegian hospital and recruited 100 references with a normal cervical cytology. Endocervical swabs were collected prior to treatment and at six (n = 77) and 12 months (n = 72) post LEEP for bacterial culture and PCR, and post LEEP for DNA testing for human papillomavirus (HPV). We compared the cervical microbiota composition before and after treatment and between women planned for LEEP vs references.ResultsThere was a reduction in the number of non-Lactobacillus bacterial species six and 12 months after LEEP compared to before treatment and a tendency towards a concomitant increase in Lactobacillus. No association between the detection of cervical bacteria, HPV persistence or cone depth was found.Women planned for LEEP carried significantly more Bacteroides spp., Gardnerella vaginalis, Mycoplasma hominis and Ureaplasma parvum as well as a greater number of bacterial species than the references.ConclusionsLocal excisional treatment appears to alter the cervical microbiota towards a less diverse microbiota. Women with CIN have a more diverse cervical microbiota compared to women with normal cervical cytology.

Journal article

Tzafetas M, Mitra A, Kalliala I, Lever S, Fotopoulou C, Farthing A, Smith JR, Martin-Hirsch P, Paraskevaidis E, Kyrgiou Met al., 2018, Fertility-sparing surgery for presumed early-stage invasive cervical cancer: a survey of practice in the United Kingdom., Anticancer Research, Vol: 38, Pages: 3641-3646, ISSN: 0250-7005

AIM: To explore current practice in fertility-sparing surgery for cervical cancer in the UK. MATERIALS AND METHODS: A web-based structured questionnaire was designed and circulated to all members of the British Gynaecological Cancer Society. RESULTS: From 111 recipients, a total of 49 responses were collected. The majority of centres treated between 20-29 cases of invasive cervical cancer surgically (21/49, 42.9%) and performed between 0-5 cases of radical trachelectomy annually (29/49, 59.2%). The vaginal approach was the one most commonly used and was offered by almost half of the centres (21/49, 42.9%); laparoscopic techniques were offered in 13 (13/49, 26.6%). The responses were divided as to whether these cases should have been referred to supra-regional centres (25/49, 51.0%). CONCLUSION: With the use of Human Papillomavirus vaccination leading to a projected decrease in the number of cervical cancer incidence, patients may need to be referred to supraregional centres in the future.

Journal article

Tzafetas M, Mitra A, Kalliala I, Bodai Z, Rosini F, Phelps D, Savage A, Lyons D, Ghaem-Maghami S, Takats Z, Kyrgiou Met al., 2018, iKnife - improving surgical outcomes in pre-invasive and invasive cervical disease, RCOG World Congress 2018, Publisher: Wiley, Pages: 17-17, ISSN: 1470-0328

Conference paper

Kyrgiou M, Athanasiou A, Kalliala IEJ, Paraskevaidi M, Mitra A, Martin-Hirsch PP, Arbyn M, Bennett P, Paraskevaidis Eet al., 2017, Obstetric outcomes after conservative treatment for cervical intraepithelial lesions and early invasive disease., Cochrane Database of Systematic Reviews, Vol: 11, ISSN: 1469-493X

BACKGROUND: The mean age of women undergoing local treatment for pre-invasive cervical disease (cervical intra-epithelial neoplasia; CIN) or early cervical cancer (stage IA1) is around their 30s and similar to the age of women having their first child. Local cervical treatment has been correlated to adverse reproductive morbidity in a subsequent pregnancy, however, published studies and meta-analyses have reached contradictory conclusions. OBJECTIVES: To assess the effect of local cervical treatment for CIN and early cervical cancer on obstetric outcomes (after 24 weeks of gestation) and to correlate these to the cone depth and comparison group used. SEARCH METHODS: We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library, 2017, Issue 5), MEDLINE (up to June week 4, 2017) and Embase (up to week 26, 2017). In an attempt to identify articles missed by the search or unpublished data, we contacted experts in the field and we handsearched the references of the retrieved articles and conference proceedings. SELECTION CRITERIA: We included all studies reporting on obstetric outcomes (more than 24 weeks of gestation) in women with or without a previous local cervical treatment for any grade of CIN or early cervical cancer (stage IA1). Treatment included both excisional and ablative methods. We excluded studies that had no untreated reference population, reported outcomes in women who had undergone treatment during pregnancy or had a high-risk treated or comparison group, or both DATA COLLECTION AND ANALYSIS: We classified studies according to the type of treatment and the obstetric endpoint. Studies were classified according to method and obstetric endpoint. Pooled risk ratios (RR) and 95% confidence intervals (CIs) were calculated using a random-effects model and inverse variance. Inter-study heterogeneity was assessed with I2 statistics. We assessed maternal outcomes that included preterm birth (PTB) (spontaneous a

Journal article

Mitra A, MacIntyre D, Lee Y, Smith A, Marchesi J, Lyons D, Bennett P, Kyrgiou Met al., 2017, THE VAGINAL MICROBIOTA AFTER EXCISIONAL TREATMENT FOR CERVICAL INTRAEPITHELIAL NEOPLASIA, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 979-979, ISSN: 1048-891X

Conference paper

kalliala I, Markozannes G, Gunter M, Paraskevaidis E, Gabra H, Mitra A, terzidou V, Martin-Hirsch P, Tsilidis K, Kyrgiou Met al., 2017, Obesity and gynaecological and obstetrical conditions: an umbrella review of the literature, British Medical Journal, Vol: 7, ISSN: 0959-8138

Objective To study the strength and validity of associations between adiposity and risk of any type of obstetric or gynaecological conditions.Design An umbrella review of meta-analyses.Data sources PubMed, Cochrane database of systematic reviews, manual screening of references for systematic reviews or meta-analyses of observational and interventional studies evaluating the association between adiposity and risk of any obstetrical or gynaecological outcome.Main outcomes Meta-analyses of cohort studies on associations between indices of adiposity and obstetric and gynaecological outcomes.Data synthesis Evidence from observational studies was graded into strong, highly suggestive, suggestive, or weak based on the significance of the random effects summary estimate and the largest study in the included meta-analysis, the number of cases, heterogeneity between studies, 95% prediction intervals, small study effects, excess significance bias, and sensitivity analysis with credibility ceilings. Interventional meta-analyses were assessed separately.Results 156 meta-analyses of observational studies were included, investigating associations between adiposity and risk of 84 obstetric or gynaecological outcomes. Of the 144 meta-analyses that included cohort studies, only 11 (8%) had strong evidence for eight outcomes: adiposity was associated with a higher risk of endometrial cancer, ovarian cancer, antenatal depression, total and emergency caesarean section, pre-eclampsia, fetal macrosomia, and low Apgar score. The summary effect estimates ranged from 1.21 (95% confidence interval 1.13 to 1.29) for an association between a 0.1 unit increase in waist to hip ratio and risk endometrial cancer up to 4.14 (3.61 to 4.75) for risk of pre-eclampsia for BMI >35 compared with <25. Only three out of these eight outcomes were also assessed in meta-analyses of trials evaluating weight loss interventions. These interventions significantly reduced the risk of caesarean section and pre

Journal article

Mitra A, Mahajan V, Macintyre D, Lee Y, Smith A, Marchesi J, Lyons D, Bennett P, Kyrgiou Met al., 2017, Comparison of vaginal microbiota sampling techniques: cytobrush versus swab, Scientific Reports, Vol: 7, ISSN: 2045-2322

Evidence suggests the vaginal microbiota (VM) may influence risk of persistent Human Papillomavirus (HPV) infection and cervical carcinogenesis. Established cytology biobanks, typically collected with a cytobrush, constitute a unique resource to study such associations longitudinally. It is plausible that compared to rayon swabs; the most commonly used sampling devices, cytobrushes may disrupt biofilms leading to variation in VM composition. Cervico-vaginal samples were collected with cytobrush and rayon swabs from 30 women with high-grade cervical precancer. Quantitative PCR was used to compare bacterial load and Illumina MiSeq sequencing of the V1-V3 regions of the 16S rRNA gene used to compare VM composition. Cytobrushes collected a higher total bacterial load. Relative abundance of bacterial species was highly comparable between sampling devices (R2 = 0.993). However, in women with a Lactobacillus-depleted, high-diversity VM, significantly less correlation in relative species abundance was observed between devices when compared to those with a Lactobacillus species-dominant VM (p = 0.0049). Cytobrush and swab sampling provide a comparable VM composition. In a small proportion of cases the cytobrush was able to detect underlying high-diversity community structure, not realized with swab sampling. This study highlights the need to consider sampling devices as potential confounders when comparing multiple studies and datasets.

Journal article

Halliwell DE, Morais CLM, Lima KMG, Trevisan J, Siggel-King MRF, Craig T, Ingham J, Martin DS, Heys K, Kyrgiou M, Mitra A, Paraskevaidis E, Theophilou G, Martin-Hirsch PL, Cricenti A, Luce M, Weightman P, Martin FLet al., 2017, An imaging dataset of cervical cells using scanning near-field optical microscopy coupled to an infrared free electron laser, SCIENTIFIC DATA, Vol: 4, ISSN: 2052-4463

Using a scanning near-field optical microscope coupled to an infrared free electron laser (SNOM-IR-FEL) in low-resolution transmission mode, we collected chemical data from whole cervical cells obtained from 5 pre-menopausal, non-pregnant women of reproductive age, and cytologically classified as normal or with different grades of cervical cell dyskaryosis. Imaging data are complemented by demography. All samples were collected before any treatment. Spectra were also collected using attenuated total reflection, Fourier-transform (ATR-FTIR) spectroscopy, to investigate the differences between the two techniques. Results of this pilot study suggests SNOM-IR-FEL may be able to distinguish cervical abnormalities based upon changes in the chemical profiles for each grade of dyskaryosis at designated wavelengths associated with DNA, Amide I/II, and lipids. The novel data sets are the first collected using SNOM-IR-FEL in transmission mode at the ALICE facility (UK), and obtained using whole cells as opposed to tissue sections, thus providing an ‘intact’ chemical profile. These data sets are suited to complementing future work on image analysis, and/or applying the newly developed algorithm to other datasets collected using the SNOM-IR-FEL approach.

Journal article

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