Publications by authors named "Maria Kyrgiou"

86 Publications

The association between obesity and weight loss after bariatric surgery on the vaginal microbiota.

Microbiome 2021 May 28;9(1):124. Epub 2021 May 28.

IRDB, Department of Metabolism, Digestion and Reproduction - Surgery and Cancer, Hammersmith Campus, Imperial College London, W12 0NN, London, UK.

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 6 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 weight loss 6-month post-surgery are most likely to have a Lactobacillus-dominant VMB. Video abstract.
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http://dx.doi.org/10.1186/s40168-021-01011-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164250PMC
May 2021

Psychological burden of covid-19 health crisis on health professionals and interventions to minimize the effect: what has history already taught us?

Riv Psichiatr 2021 Jan-Feb;56(2):57-63

Department of Speech and Language Therapy, School of Health Sciences, University of Ioannina, Greece.

Health professionals have been at the frontline of the health service since the outbreak of covid-19, responding promptly to diagnose, support and treat infected patients. World Health Organization (WHO) has already praised their contribution and their essential role in controlling this disease. Some of the main concerns of covid-19's impact to health service staff include work overload, exhaustion, and high risk of self-infection or transmission to family members. Moreover, during the pandemic, caregivers' mental health inevitably becomes vulnerable, with salient stress and anxiety-related symptoms. Uncertainty, fear of contagion, guilt, hopelessness, stigmatization and, in some cases, long-term post-traumatic stress disorder (PTSD) are few of the potential effects posed by this outbreak on health workers. In this review, lessons learnt from previous global crises or pandemics on the psychological impact of health workers are presented. History could potentially provide essential information on how to best manage, support and optimize our approach to this highly appreciated and much needed group of professionals. Targeted and prompt interventions could reduce the psychological strain of health professionals, thus, further improving provided patient care. Covid-19 is an on-going health crisis and this work, even though generated by limited existing data, could be used to inform governments and/or institutions and lead on decisions and changes in current guidelines.
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http://dx.doi.org/10.1708/3594.35763DOI Listing
June 2021

Genetic variation in cervical preinvasive and invasive disease: a genome-wide association study.

Lancet Oncol 2021 04;22(4):548-557

Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK; Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK; West London Gynaecological Cancer Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK. Electronic address:

Background: Most uterine cervical high-risk human papillomavirus (HPV) infections are transient, with only a small fraction developing into cervical cancer. Family aggregation studies and heritability estimates suggest a significant inherited genetic component. Candidate gene studies and previous genome-wide association studies (GWASs) report associations between the HLA region and cervical cancer. Adopting a genome-wide approach, we aimed to compare genetic variation in women with invasive cervical cancer and cervical intraepithelial neoplasia (CIN) grade 3 with that in healthy controls.

Methods: We did a GWAS in a cohort of unrelated European individuals using data from UK Biobank, a population-based cohort including 273 377 women aged 40-69 years at recruitment between March 13, 2006, and Oct 1, 2010. We used an additive univariate logistic regression model to analyse genetic variants associated with invasive cervical cancer or CIN3. We sought replication of candidate associations in FinnGen, a large independent dataset of 128 123 individuals. We also did a two-sample mendelian randomisation approach to explore the role of risk factors in the genetic risk of cervical cancer.

Findings: We included 4769 CIN3 and invasive cervical cancer case samples and 145 545 control samples in the GWAS. Of 9 600 464 assayed and imputed single-nucleotide polymorphisms (SNPs), six independent variants were associated with CIN3 and invasive cervical cancer. These included novel loci rs10175462 (PAX8; odds ratio [OR] 0·87, 95% CI 0·84-0·91; p=1·07 × 10) and rs27069 (CLPTM1L; 0·88, 0·84-0·92; p=2·51 × 10), and previously reported signals at rs9272050 (HLA-DQA1; 1·27, 1·21-1·32; p=2·51 × 10), rs6938453 (MICA; 0·79, 0·75-0·83; p=1·97 × 10), rs55986091 (HLA-DQB1; 0·66, 0·60-0·72; p=6·42 × 10), and rs9266183 (HLA-B; 0·73, 0·64-0·83; p=1·53 × 10). Three SNPs were replicated in the independent Finnish dataset of 1648 invasive cervical cancer cases: PAX8 (rs10175462; p=0·015), CLPTM1L (rs27069; p=2·54 × 10), and HLA-DQA1 (rs9272050; p=7·90 × 10). Mendelian randomisation further supported the complementary role of smoking (OR 2·46, 95% CI 1·64-3·69), older age at first pregnancy (0·80, 0·68-0·95), and number of sexual partners (1·95, 1·44-2·63) in the risk of developing cervical cancer.

Interpretation: Our results provide new evidence for the genetic susceptibility to cervical cancer, specifically the PAX8, CLPTM1L, and HLA genes, suggesting disruption in apoptotic and immune function pathways. Future studies integrating host and viral, genetic, and epigenetic variation, could further elucidate complex host-viral interactions.

Funding: NIHR Imperial BRC Wellcome 4i Clinician Scientist Training Programme.
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http://dx.doi.org/10.1016/S1470-2045(21)00028-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008734PMC
April 2021

Type 2 Diabetes and Cancer: An Umbrella Review of Observational and Mendelian Randomization Studies.

Cancer Epidemiol Biomarkers Prev 2021 Jun 18;30(6):1218-1228. Epub 2021 Mar 18.

Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.

Background: Type 2 diabetes mellitus (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 summarize the evidence on T2DM and cancer and evaluate the validity of associations from both observational and Mendelian randomization (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 cancers.

Impact: Potential causal associations were identified for genetically predicted T2DM and fasting insulin concentrations and risk of endometrial, pancreas, kidney, breast, lung, and cervical cancers.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1245DOI Listing
June 2021

Fostering Prevention of Cervical Cancer by a Correct Diagnosis of Precursors: A Structured Case-Based Colposcopy Course in Finland, Norway and UK.

Cancers (Basel) 2020 Oct 30;12(11). Epub 2020 Oct 30.

Department of Obstetrics and Gynaecology, Helsinki University Hospital and Helsinki University, 00290 Helsinki, Finland.

High-quality colposcopy is essential in cervical cancer prevention. We performed a multicentre prospective interventional pilot-study, evaluating the effect of a six-hour case-based colposcopy course on short- and long-term learning of colposcopy-related knowledge, diagnostic accuracy levels and confidence. We recruited 213 colposcopists participating in three European Federation of Colposcopy (EFC) basic colposcopy courses (Finland, Norway, UK). The study consisted of three tests with identical content performed before, after and 2 months after the course, including ten colposcopic images, ten patient cases and scales for marking confidence in the answers. Outcome measures where mean scores in correct case-management, diagnosis (including high-grade lesion recognition), transformation-zone recognition and confidence in answers. Results were compared between the three tests and stratified according to experience. Mean test scores improved after the course for all participants. The increase was highest for beginners. Confidence in answers improved and the number of colposcopists showing high confidence with low scores decreased. A structured case-based course improves skills and confidence especially for inexperienced colposcopists; however, trainers should be aware of the risk of overconfidence. To complement theoretical training, further hands-on training including high-quality feedback is recommended. Conclusions drawn from long-term learning are limited due to the low participation in the follow-up test.
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http://dx.doi.org/10.3390/cancers12113201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692698PMC
October 2020

Laser-assisted rapid evaporative ionisation mass spectrometry (LA-REIMS) as a metabolomics platform in cervical cancer screening.

EBioMedicine 2020 Oct 25;60:103017. Epub 2020 Sep 25.

Department of Metabolism, Digestion and Reproduction & Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, 665 Sir Alexander Fleming Building, South Kensington Campus, London W12 0NN, United Kingdom; Imperial College Healthcare NHS Trust, London, United Kingdom. Electronic address:

Background: The 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.

Methods: In 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.

Findings: In 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.

Interpretation: This 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.

Funding: Work was funded by the MRC Imperial Confidence in Concept Scheme, Imperial College Healthcare Charity, British Society for Colposcopy and Cervical Pathology, National Research Development and Innovation Office of Hungary, Waters corporation and NIHR BRC.
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http://dx.doi.org/10.1016/j.ebiom.2020.103017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522750PMC
October 2020

Organoid models in gynaecological oncology research.

Cancer Treat Rev 2020 Nov 1;90:102103. Epub 2020 Sep 1.

Department of Surgery and Cancer & Department of Digestion, Metabolism and Reproduction, Faculty of Medicine, Imperial College London, London W12 0NN, UK; Queen Charlotte's and Chelsea - Hammersmith Hospital, Imperial College Healthcare NHS Trust, London W12 0HS, UK. Electronic address:

Cell culture and animal models represent experimental cornerstones for the investigation of tissue, organ and body physiology in the context of gynaecological research. However, their ability to accurately reflect human mechanisms in vivo is limited. The development of organoid technologies has begun to address this limitation by providing platforms ex vivo that resemble the phenotype and genotype of the multi-cellular tissue from which they were derived more accurately. In this review, we discuss advances in organoid derivation from endometrial, ovarian, fallopian tube and cervical tissue, both benign and malignant, the manipulation of organoid microenvironment to preserve stem cell populations and achieve long-term expansion and we explore the morphological and molecular kinship of organoids to parent tissue. Apart from providing new insight into mechanisms of carcinogenesis, gynaecological cancer-derived organoids can be utilised as tools for drug screening of chemotherapeutic and hormonal compounds where they exhibit interpatient variability consistent with states in vivo and xenografted tumours allowing for patient-tailored treatment strategies. Bridging organoid with bioengineering accomplishments is clearly the way forward to the generation of organoid-on-a-chip technologies enhancing the robustness of the model and its translational potential. Undeniably, organoids are expected to stand their ground in the years to come and revolutionize development and disease modelling studies.
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http://dx.doi.org/10.1016/j.ctrv.2020.102103DOI Listing
November 2020

Bisphenol-A and polycystic ovary syndrome: a review of the literature.

Rev Environ Health 2020 Nov 14;35(4):323-331. Epub 2020 Jul 14.

Department of Metabolism, Digestion and Reproduction and Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.

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.
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http://dx.doi.org/10.1515/reveh-2020-0032DOI Listing
November 2020

The European response to the WHO call to eliminate cervical cancer as a public health problem.

Int J Cancer 2021 01 4;148(2):277-284. Epub 2020 Aug 4.

International Agency for Research on Cancer, Lyon, France.

The age-standardised incidence of cervical cancer in Europe varies widely by country (between 3 and 25/100000 women-years) in 2018. Human papillomavirus (HPV) vaccine coverage is low in countries with the highest incidence and screening performance is heterogeneous among European countries. A broad group of delegates of scientific professional societies and cancer organisations endorse the principles of the WHO call to eliminate cervical cancer as a public health problem, also in Europe. All European nations should, by 2030, reach at least 90% HPV vaccine coverage among girls by the age of 15 years and also boys, if cost-effective; they should introduce organised population-based HPV-based screening and achieve 70% of screening coverage in the target age group, providing also HPV testing on self-samples for nonscreened or underscreened women; and to manage 90% of screen-positive women. To guide member states, a group of scientific professional societies and cancer organisations engage to assist in the rollout of a series of concerted evidence-based actions. European health authorities are requested to mandate a group of experts to develop the third edition of European Guidelines for Quality Assurance of Cervical Cancer prevention based on integrated HPV vaccination and screening and to monitor the progress towards the elimination goal. The occurrence of the COVID-19 pandemic, having interrupted prevention activities temporarily, should not deviate stakeholders from this ambition. In the immediate postepidemic phase, health professionals should focus on high-risk women and adhere to cost-effective policies including self-sampling.
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http://dx.doi.org/10.1002/ijc.33189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754400PMC
January 2021

Role of Colposcopy after Treatment for Cervical Intraepithelial Neoplasia.

Cancers (Basel) 2020 Jun 24;12(6). Epub 2020 Jun 24.

Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland.

Colposcopy is often used in follow-up after treatment for cervical intraepithelial neoplasia (CIN) despite its marked inter-observer variability and low sensitivity. Our objective was to assess the role of colposcopy in post-treatment follow-up in comparison to hrHPV (high-risk human papillomavirus) testing, cytology, and cone margin status. Altogether, 419 women treated for histological high-grade lesion (HSIL) with large loop excision of the transformation zone (LLETZ) attended colposcopy with cytology and hrHPV test at six months. Follow-up for recurrence of HSIL continued for 24 months. Colposcopy was considered positive if colposcopic impression was recorded as high grade and cytology if HSIL, ASC-H (atypical squamous cells, cannot exclude HSIL), or AGC-FN (atypical glandular cells, favor neoplasia) were present. Overall, 10 (10/419, 2.4%) recurrent HSIL cases were detected, 5 at 6 months and 5 at 12 months. Colposcopic impression was recorded at 407/419 6-month visits and was positive for 11/407 (2.7%). None of them had recurrent lesions, resulting in 0% sensitivity and 97% specificity for colposcopy. Sensitivity for the hrHPV test at 6 months was 100% and specificity 85%, for cytology 40% and 99%, and for margin status at treatment 60% and 82%, respectively. While the hrHPV test is highly sensitive in predicting recurrence after local treatment for CIN, colposcopy in an unselected population is not useful in follow-up after treatment of CIN.
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http://dx.doi.org/10.3390/cancers12061683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352967PMC
June 2020

Cervical screening: ESGO-EFC position paper of the European Society of Gynaecologic Oncology (ESGO) and the European Federation of Colposcopy (EFC).

Br J Cancer 2020 08 8;123(4):510-517. Epub 2020 Jun 8.

Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

This paper summarises the position of ESGO and EFC on cervical screening based on existing guidelines and opinions of a team of lead experts. HPV test is replacing cytology as this offers greater protection against cervical cancer and allows longer screening intervals. Only a dozen of HPV tests are considered as clinically validated for screening. The lower specificity of HPV test dictates the use of triage tests that can select women for colposcopy. Reflex cytology is currently the only well validated triage test; HPV genotyping and p16 immunostaining may be used in the future, although methylation assays and viral load also look promising. A summary of quality assurance benchmarks is provided, and the importance to audit the screening histories of women who developed cancer is noted as a key objective. HPV-based screening is more cost-effective than cytology or cotesting. HPV-based screening should continue in the post-vaccination era. Only a fraction of the female population is vaccinated, and this varies across countries. A major challenge will be to personalise screening frequency according to vaccination status. Still the most important factor for successful prevention by screening is high population coverage and organised screening. Screening with self-sampling to reach under-screened women is promising.
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http://dx.doi.org/10.1038/s41416-020-0920-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434873PMC
August 2020

Detecting Endometrial Cancer by Blood Spectroscopy: A Diagnostic Cross-Sectional Study.

Cancers (Basel) 2020 May 16;12(5). Epub 2020 May 16.

Division of Cancer Sciences, University of Manchester, Manchester M13 9WL, UK.

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 ( = 342), its precursor lesion atypical hyperplasia ( = 68) and healthy controls ( = 242, total = 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.
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http://dx.doi.org/10.3390/cancers12051256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281323PMC
May 2020

Alterations of HPV-Related Biomarkers after Prophylactic HPV Vaccination. A Prospective Pilot Observational Study in Greek Women.

Cancers (Basel) 2020 May 5;12(5). Epub 2020 May 5.

Department of Obstetrics & Gynaecology, University Hospital of Larisa, Mezourlo, 41334 Larisa, Greece.

The objective of this study was to investigate the hypothesis that HPV vaccination administered in patients with low-grade (LG) cytology shortly after an initial colposcopic assessment could prospectively alter HPV-related biomarkers. This was a prospective pilot observational study involving women attending a colposcopy clinic for evaluation of abnormal LG cytology that were advised to undergo HPV vaccination and proceeded accordingly. These women were compared with a matched unvaccinated group. Women requiring cervical biopsies or CIN treatment were excluded.

Intervention: A full three-dose HPV vaccination was undertaken with either the 2-valent or the 4-valent anti-HPV VLP vaccine. LBC samples were obtained prior and after the completion of the vaccination regimen and tested for HPV DNA genotyping (CLART-2 HPV test) and E6 and E7 mRNA (NASBA technique).

Results: Alterations of HPV-related biomarkers at a colposcopy reassessment appointment 12 months later.

Analysis: The -values, relative risk (RR), absolute relative risk (ARR), number needed to treat (NNT) and 95% confidence intervals for each biomarker in each group were assessed.

Results: A total of 309 women were included in the analysis. One hundred fifty-two women received the vaccine. HPV vaccination reduced in a statistically significant manner ( < 0.05) HPV DNA positivity rates for genotypes 16, 18, and 31, RR = 1.6 (95% CI: 1.1 to 2.3), RR = 1.7 (95% CI: 1.1 to 2.8), and RR = 1.8 (95% CI: 1.0 to 2.9), in women who only tested DNA-positive for HPV16, 18, and 31 genotypes, respectively, prior to vaccination. A less pronounced, statistically insignificant reduction was shown for women who tested positive for both HPV DNA and mRNA E6 and E7 expression for HPV16, 18, and 33 subtypes. Statistically significant reduction in HPV mRNA positivity was solely documented for genotype 31 ( = 0.0411).

Conclusions: HPV vaccination appears to significantly affect the rates of HPV16, 18, and 31 DNA-positive infections in the population testing HPV DNA-positive for the aforementioned genotypes. The above findings deserve verification in larger cohorts.
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http://dx.doi.org/10.3390/cancers12051164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281708PMC
May 2020

Cervical Pathology Following HPV Vaccination in Greece: A 10-year HeCPA Observational Cohort Study.

In Vivo 2020 May-Jun;34(3):1445-1449

Institute of Reproductive and Developmental Biology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, U.K.

Background: In Greece the population-level impact of HPV vaccination is unknown due to lack of official registries. This study presents in a pragmatic frame the comparison of cervical pathology data between HPV-vaccinated and unvaccinated women referred for colposcopy.

Patients And Methods: This is an observational prospective cohort study performed in 7 academic Obstetrics and 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: HPV vaccination at a proper age can markedly reduce development of severe cervical precancers and consequently the need for treatment, as well as their long-term related obstetrical morbidity.
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http://dx.doi.org/10.21873/invivo.11927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279786PMC
February 2021

The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions.

Nat Commun 2020 04 24;11(1):1999. Epub 2020 Apr 24.

Institute for Reproductive and Developmental Biology, Imperial College, Hammersmith Hospital Campus, London, W12 0NN, UK.

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.
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http://dx.doi.org/10.1038/s41467-020-15856-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181700PMC
April 2020

The intelligent knife (iKnife) and its intraoperative diagnostic advantage for the treatment of cervical disease.

Proc Natl Acad Sci U S A 2020 03 16;117(13):7338-7346. Epub 2020 Mar 16.

Department of Gut, Metabolism and Reproduction, Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, London SW7 2DD, United Kingdom;

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 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.
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http://dx.doi.org/10.1073/pnas.1916960117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132269PMC
March 2020

Pathways Involved in Premature Ovarian Failure: A Systematic Review of Experimental Studies.

Curr Pharm Des 2020 ;26(18):2087-2095

Department of Obstetrics and Gynecology, Ioannina State General Hospital G. Chatzikosta, Ioannina, Greece.

Premature ovarian failure (POF), which may be undetectable for a long time, is associated with impaired fertility. The mechanisms involved in the pathogenesis of POF as well as the concomitant treatments are still unclear. Although many data exist, mainly produced by the study of transgenic animals under various experimental conditions, they remain fragmented. A systematic review of the pathways involved in premature ovarian failure was conducted. Data extraction was performed from experimental studies until 2019. The molecular processes and their correlation with the follicular developmental stage have been described. Furthermore, the effects in other cells, such as oocytes, granulosa and theca cells have been reported. An overall estimation was conducted.
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http://dx.doi.org/10.2174/1381612826666200316160145DOI Listing
December 2020

Use of the Aptima mRNA high-risk human papillomavirus (HR-HPV) assay compared to a DNA HR-HPV assay in the English cervical screening programme: a decision tree model based economic evaluation.

BMJ Open 2020 03 8;10(3):e031303. Epub 2020 Mar 8.

Aquarius Population Health, London, UK

Objective: To estimate the impact of using the Aptima messenger RNA (mRNA) high-risk human papilloma virus (HR-HPV) assay versus a DNA HR-HPV assay in a primary HPV cervical screening programme.

Design: One hypothetical cohort followed for 3 years through HPV primary cervical screening.

Setting: England.

Participants: A hypothetical cohort of women aged 25-65 years tested in the National Health Service (NHS) Cervical Screening Programme (CSP) for first call or routine recall testing.

Methods: A decision tree parameterised with data from the CSP (2017/18) and the HORIZON study. Uncertainty analyses were conducted using data from the FOCAL and GAST studies, other DNA HPV tests in addition to one-way and probabilistic sensitivity and scenarios analyses, to test the robustness of results.

Interventions: Aptima mRNA HR-HPV assay and a DNA HR-HPV assay (cobas 4800 HPV assay).

Main Outcome Measures: Primary: total colposcopies and total costs for the cohort. Secondary: total HPV and cytology tests, number lost to follow-up.

Results: At baseline for a population of 2.25 million women, an estimated £15.4 million (95% credibility intervals (CI) £6.5 to 24.1 million) could be saved and 28 009 (95% CI 27 499 to 28 527) unnecessary colposcopies averted if Aptima mRNA assays are used instead of a DNA assay, with 90 605 fewer unnecessary HR-HPV and 253 477 cytology tests performed. These savings are due to a lower number of HPV positive samples in the mRNA arm. When data from other primary HPV screening trials were compared, results indicated that using the Aptima mRNA assay generated cost savings and reduced testing in every scenario.

Conclusion: Using the Aptima mRNA assay versus a DNA assay would almost certainly yield cost savings and reduce unnecessary testing and procedures, benefiting the NHS and women in the CSP.
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http://dx.doi.org/10.1136/bmjopen-2019-031303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064071PMC
March 2020

Proteomic analysis of malignant and benign endometrium according to obesity and insulin-resistance status using Reverse Phase Protein Array.

Transl Res 2020 04 27;218:57-72. Epub 2019 Dec 27.

Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, London, UK; Queen Charlotte's and Chelsea - Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK. Electronic address:

Obesity and hyperinsulinemia are known risk factors for endometrial cancer, yet the biological pathways underlying this relationship are incompletely understood. This study investigated protein expression in endometrial cancer and benign tissue and its correlation with obesity and insulin resistance. One hundred and seven women undergoing hysterectomy for endometrial cancer or benign conditions provided a fasting blood sample and endometrial tissue. We performed proteomic expression according to body mass index, insulin resistance, and serum marker levels. We used linear regression and independent t test for statistical analysis. Proteomic data from 560 endometrial cancer cases from The Cancer Genome Atlas (TCGA) databank were used to assess reproducibility of results. One hundred and twenty seven proteins were significantly differentially expressed between 66 cancer and 26 benign patients. Protein expression involved in cell cycle progression, impacting cytoskeletal dynamics (PAK1) and cell survival (Rab 25), were most significantly altered. Obese women with cancer had increased PRAS40_pT246; a downstream marker of increased PI3K-AKT signaling. Obese women without cancer had increased mitogenic and antiapoptotic signaling by way of upregulation of Mcl-1, DUSP4, and Insulin Receptor-b. This exploratory study identified a number of candidate proteins specific to endometrioid endometrial cancer and benign endometrial tissues. Obesity and insulin resistance in women with benign endometrium leads to specific upregulation of proteins involved in insulin and driver oncogenic signaling pathways such as the PI3K-AKT-mTOR and growth factor signaling pathways which are mitogenic and also disruptive to metabolism.
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http://dx.doi.org/10.1016/j.trsl.2019.12.003DOI Listing
April 2020

Transvaginal laparoscopic salpingo-oophorectomy: an oncological risk-reducing procedure.

Future Sci OA 2019 Nov 5;6(1):FSO429. Epub 2019 Nov 5.

Frimley Health NHS Foundation Trust, Portsmouth Road, Frimley, Camberley GU16 7UJ, United Kingdom.

Aim: Since the first natural orifice transluminal endoscopic surgery procedure, renewed interest has arisen in further developing and advancing minimal access surgery. We introduce a natural orifice endoscopic approach for a bilateral salpingo-oophorectomy.

Patients & Methods: Using the vagina as a natural orifice, we performed a transvaginal laparoscopic salpingo-oophorectomy to remove bilateral adnexa in patients with a strong family history of ovarian and/or breast cancer and those positive for mutation.

Results: Total 36 women underwent transvaginal laparoscopic salpingo-oophorectomy. Conversion to routine laparoscopy was required in eight patients to complete the operation. No peri-operative complications were noted.

Conclusion: We describe a novel approach in gynecological surgery. Our technique proved to be safe and efficient with the advantage of avoiding any abdominal scars.
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http://dx.doi.org/10.2144/fsoa-2019-0089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920739PMC
November 2019

Exploring the acceptability and feasibility of patient-initiated follow-up for women treated for stage I endometrial cancer.

Eur J Oncol Nurs 2020 Feb 28;44:101704. Epub 2019 Nov 28.

Department of Surgery and Cancer, Institute of Reproductive and Development Biology, Faculty of Medicine, Imperial College London, W12 0NN, United Kingdom; Queen Charlotte's and Chelsea-Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, W12 0HS, United Kingdom. Electronic address:

Purpose: There is a strong shift away from hospital-based approaches to follow-up after active treatment for cancer with supported self-management being promoted as an approach to long term recovery. We aimed to determine the acceptability and feasibility of patient-initiated follow-up (PIFU), supported by a self-management approach, for patients treated for Stage I endometrial cancer.

Methods: A mixed methods study was undertaken. Participants were asked to forego hospital outpatient follow-up appointments, supported by a self-management approach. Outcome measures included satisfaction with information and service, psychological morbidity, quality of life and preferences for follow-up. Qualitative interviews were carried out with study participants to determine their views on follow-up in general and PIFU in particular.

Results: We recruited 17 patients. High levels of satisfaction were evident with no physical or psychological detriment. Self-management was a favoured option. Participants questioned the value of hospital follow-up and were willing to engage in self-management if they knew who to contact if they had a problem and were aware of the signs and symptoms of recurrence. However, uptake to the study was low and further work is needed to explore if recruitment to a randomised controlled trial (RCT) is a viable option.

Conclusions: Alternative approaches to hospital-based follow-up need to demonstrate that patients feel supported, knowing what symptoms to report and to whom. This study shows acceptability of a supported self-management approach but raises some concerns about the feasibility of recruitment to a future RCT.
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http://dx.doi.org/10.1016/j.ejon.2019.101704DOI Listing
February 2020

The use of human papillomavirus DNA methylation in cervical intraepithelial neoplasia: A systematic review and meta-analysis.

EBioMedicine 2019 Dec 12;50:246-259. Epub 2019 Nov 12.

Department of Surgery and Cancer, 3rd Floor IRDB, Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 ONN, London, UK; West London Gynaecology Cancer Centre, Hammersmith Hospital, Imperial Healthcare NHS Trust, UK. Electronic address:

Background: Methylation 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 detecting high-grade cervical intra-epithelial neoplasia (CIN).

Methods: We 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 in duplicate and requested from authors where necessary. Random-effects models and a bivariate mixed-effects binary regression model were applied to determine pooled effect estimates.

Findings: 44 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 squamous intra-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 difference in 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)).

Interpretation: Higher 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 is limited by the need for a multi-genotype and standardised assays. Next-generation multiplex HPV sequencing assays are under development and allow potential for rapid, automated and low-cost methylation testing.

Funding: NIHR, Genesis Research Trust, Imperial Healthcare Charity, Wellcome Trust NIHR Imperial BRC, European Union's Horizon 2020.
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http://dx.doi.org/10.1016/j.ebiom.2019.10.053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921230PMC
December 2019

Prophylactic vaccination against human papillomaviruses to prevent vulval and vaginal cancer and their precursors.

Expert Rev Vaccines 2019 11 2;18(11):1157-1166. Epub 2019 Dec 2.

Unit of Cancer Epidemiology, Belgian Cancer Centre, Scientific Institute of Public Health, Brussels, Belgium.

: Safety and efficacy of prophylactic HPV vaccines against HPV infection and associated cervical cancers and precursors is well documented in the literature; however, their efficacy against vulval and vaginal endpoints has not been previously assessed.: Published results of trials involving licensed HPV vaccines were included. Main efficacy outcomes were histologically confirmed high-grade vulval and vaginal precancer distinguishing those associated with vaccine HPV types and any vulval and vaginal precancerous lesions. Exposure groups included women aged 15-26 or 24-45 years being initially negative for high-risk HPV (hrHPV), negative for the HPV vaccine types, and women unselected by HPV status.: Our results show that the HPV vaccines are equally highly efficacious against vulval/vaginal disease as previously noted for cervical disease. The vaccines demonstrated excellent protection against high-grade vulval and vaginal lesions caused by vaccine-related HPV types among young women who were not initially infected with hrHPV types or types included in the vaccines (vaccine efficacies more than 90%). No protection against high-grade vulval and vaginal lesions associated with HPV16/18 was observed for mid-adult women. Trials were not powered to address protection against invasive cancers.
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http://dx.doi.org/10.1080/14760584.2019.1692658DOI Listing
November 2019

Comparative fertility and pregnancy outcomes after local treatment for cervical intraepithelial neoplasia and stage 1a1 cervical cancer: protocol for a systematic review and network meta-analysis from the CIRCLE group.

BMJ Open 2019 10 21;9(10):e028009. Epub 2019 Oct 21.

Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Institute of Reproductive and Developmental Biology, London, UK

Introduction: There are several local treatment methods for cervical intraepithelial neoplasia that remove or ablate a cone-shaped part of the uterine cervix. There is evidence to suggest that these increase the risk of preterm birth (PTB) and that this is higher for techniques that remove larger parts of the cervix, although the data are conflicting. We present a protocol for a systematic review and network meta-analysis (NMA) that will update the evidence and compare all treatments in terms of fertility and pregnancy complications.

Methods And Analysis: We will search electronic databases (CENTRAL, MEDLINE, EMBASE) from inception till October 2019, in order to identify randomised controlled trials (RCTs) and cohort studies comparing the fertility and pregnancy outcomes among different excisional and ablative treatment techniques and/or to untreated controls. The primary outcome will be PTB (<37 weeks). Secondary outcomes will include severe or extreme PTB, prelabour rupture of membranes, low birth weight (<2500 g), neonatal intensive care unit admission, perinatal mortality, total pregnancy rates, first and second trimester miscarriage. We will search for published and unpublished studies in electronic databases, trial registries and we will hand-search references of published papers. We will assess the risk of bias in RCTs and cohort studies using tools developed by the Cochrane collaboration. Two investigators will independently assess the eligibility, abstract the data and assess the risk of bias of the identified studies. For each outcome, we will perform a meta-analysis for each treatment comparison and an NMA once the transitivity assumption holds, using the OR for dichotomous data. We will use CINeMA (Confidence in Network meta-analysis) to assess the quality of the evidence for the primary outcome.

Ethics And Dissemination: Ethical approval is not required. Results will be disseminated to academic beneficiaries, medical practitioners, patients and the public.

Prospero Registration Number: CRD42018115495.
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http://dx.doi.org/10.1136/bmjopen-2018-028009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803140PMC
October 2019

Erratum to "Proportion of cervical excision for cervical intraepithelial neoplasia as a predictor of pregnancy outcomes"[Int J Gynecol Obstet 128(2015) 141-147].

Int J Gynaecol Obstet 2019 Sep 19;146(3):392. Epub 2019 Jul 19.

Department of Obstetrics and Gynecology-Gynecological Oncology, University Hospital of Ioannina, Ioannina, Greece.

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http://dx.doi.org/10.1002/ijgo.12905DOI Listing
September 2019

Comparative efficacy and complication rates after local treatment for cervical intraepithelial neoplasia and stage 1a1 cervical cancer: protocol for a systematic review and network meta-analysis from the CIRCLE Group.

BMJ Open 2019 08 2;9(8):e028008. Epub 2019 Aug 2.

Department of Surgery and Cancer, Faculty of Medicine, Institute of Reproductive and Developmental Biology, Imperial College London, London, UK

Introduction: Local treatments for cervical intraepithelial neoplasia (CIN) and microinvasive disease remove or ablate a cone-shaped part of the uterine cervix containing the abnormal cells. A trend toward less radical techniques has raised concerns that this may adversely impact the rates of precancerous and cancerous recurrence. However, there has been no strong evidence to support such claims. We hereby describe a protocol of a systematic review and network meta-analysis that will update the evidence and compare all relevant treatments in terms of efficacy and complications.

Methods And Analysis: Literature searches in electronic databases (CENTRAL, MEDLINE, EMBASE) or trial registries will identify published and unpublished randomised controlled trials (RCTs) and cohort studies comparing the efficacy and complications among different excisional and ablative techniques. The excisional techniques include cold knife, laser or Fischer cone, large loop or needle excision of the transformation zone and the ablative radical point diathermy, cryotherapy, cold coagulation or laser ablation. The primary outcome will be residual/recurrent disease defined as abnormal histology or cytology of any grade, while secondary outcomes will include treatment failure rates defined as high-grade histology or cytology, histologically confirmed CIN1+ or histologically confirmed CIN2+, human papillomavirus positivity rates, involved margins rates, bleeding and cervical stenosis rates. We will assess the risk of bias in RCTs and observational studies using tools developed by the Cochrane Collaboration. Two authors will independently assess study eligibility, abstract the data and assess the risk of bias. Random-effects meta-analyses and network meta-analyses will be conducted using the OR for dichotomous outcomes and the mean difference for continuous outcomes. The quality of the evidence for the primary outcome will be assessed using the CINeMA (Confidence In Network Meta-Analysis) tool.

Ethics And Dissemination: Ethical approval is not required. We will disseminate findings to clinicians, policy-makers, patients and the public.

Prospero Registration Number: CRD42018115508.
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http://dx.doi.org/10.1136/bmjopen-2018-028008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687014PMC
August 2019

Maximal-Effort Cytoreductive Surgery for Ovarian Cancer Patients with a High Tumor Burden: Variations in Practice and Impact on Outcome.

Ann Surg Oncol 2019 Sep 26;26(9):2943-2951. Epub 2019 Jun 26.

Department of Surgery and Cancer, Imperial College London and West London Gynecological Cancer Centre, Imperial College NHS Trust, London, UK.

Background: This study aimed to compare the outcomes of two distinct patient populations treated within two neighboring UK cancer centers (A and B) for advanced epithelial ovarian cancer (EOC).

Methods: A retrospective analysis of all new stages 3 and 4 EOC patients treated between January 2013 and December 2014 was performed. The Mayo Clinic surgical complexity score (SCS) was applied. Cox regression analysis identified the impact of treatment methods on survival.

Results: The study identified 249 patients (127 at center A and 122 in centre B) without significant differences in International Federation of Gynecology and Obstetrics (FIGO) stage (FIGO 4, 29.7% at centers A and B), Eastern Cooperative Oncology Group (ECOG) performance status (ECOG < 2, 89.9% at centers A and B), or histology (serous type in 84.1% at centers A and B). The patients at center A were more likely to undergo surgery (87% vs 59.8%; p < 0.001). The types of chemotherapy and the patients receiving palliative treatment alone were equivalent between the two centers (3.6%). The median SCS was significantly higher at center A (9 vs 2; p < 0.001) with greater tumor burden (9 vs 6 abdominal fields involved; p < 0.001), longer median operation times (285 vs 155 min; p < 0.001), and longer hospital stays (9 vs 6 days; p < 0.001), but surgical morbidity and mortality were equivalent. The independent predictors of reduced overall survival (OS) were non-serous histology (hazard ratio [HR], 1.6; 95% confidence interval [CI] 1.04-2.61), ECOG higher than 2 (HR, 1.9; 95% CI 1.15-3.13), and palliation alone (HR, 3.43; 95% CI 1.51-7.81). Cytoreduction, of any timing, had an independent protective impact on OS compared with chemotherapy alone (HR, 0.31 for interval surgery and 0.39 for primary surgery), even after adjustment for other prognostic factors.

Conclusions: Incorporating surgery into the initial EOC management, even for those patients with a greater tumor burden and more disseminated disease, may require more complex procedures and more resources in terms of theater time and hospital stay, but seems to be associated with a significant prolongation of the patients overall survival compared with chemotherapy alone.
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http://dx.doi.org/10.1245/s10434-019-07516-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682567PMC
September 2019

Human papillomavirus vaccination: The ESGO-EFC position paper of the European society of Gynaecologic Oncology and the European Federation for colposcopy.

Eur J Cancer 2019 07 1;116:21-26. Epub 2019 Jun 1.

Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Vaccines against human papillomavirus (HPV) are available in Europe since 2006. They have been highly effective in preventing infection and disease caused by the vaccine types. Clinical efficacy data are available for cervical, vulvovaginal and anal precancer and invasive cervical cancer. Disease reduction is best with early vaccination and a coverage of more than 70%. Gender-neutral vaccination provides direct protection for all men and improves the coverage. A good coverage is followed by herd protection of the unvaccinated men and women. School-based programs appear to be most effective; under the age of 15 years, two doses with an interval of 6-12 months are sufficient. From the age of 15 years, the standard regimen with three doses is recommended. A broad catch-up program for young adult women and men improves the effectiveness. The vaccines are also effective in sexually active women and men with previous but cleared infections. Vaccination in addition to local treatment of HPV-related disease appears to reduce recurrent or subsequent HPV-related disease. Combination of HPV vaccination and screening with HPV testing is the most effective approach to prevention of cervical cancer. The screening intervals may increase in the vaccinated cohorts. The upper age limit for vaccination remains to be evaluated, is country specific and depends on cost-effectiveness. The European Society of Gynaecologic Oncology and the European Federation for Colposcopy strongly support gender-neutral vaccination programs for children and young adolescents, with a catch-up program for young adults.
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http://dx.doi.org/10.1016/j.ejca.2019.04.032DOI Listing
July 2019

Cervical microbiota in women with cervical intra-epithelial neoplasia, prior to and after local excisional treatment, a Norwegian cohort study.

BMC Womens Health 2019 02 6;19(1):30. Epub 2019 Feb 6.

Department of Gynecology and Obstetrics, Østfold Hospital Trust, Kalnes, Norway.

Background: Local 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.

Methods: Between 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.

Results: There 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.

Conclusions: Local 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.
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http://dx.doi.org/10.1186/s12905-019-0727-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364458PMC
February 2019