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

Introduction Human papillomavirus (HPV) is necessary but not sufficient for cervical cancer development. During cervical carcinogenesis, methylation levels increase across host and HPV DNA. DNA methylation has been proposed as a test to diagnose cervical intraepithelial neoplasia (CIN); we present a protocol to evaluate the accuracy of methylation markers to detect high-grade CIN and cervical cancer. Methods and analysis We will search electronic databases (Medline, Embase and Cochrane Library), from inception, to identify studies examining DNA methylation as a diagnostic marker for CIN or cervical cancer, in a cervical screening population. The primary outcome will be to assess the diagnostic test accuracy of host and HPV DNA methylation for high-grade CIN; the secondary outcomes will be to examine the accuracy of different methylation cut-off thresholds, and accuracy in high-risk HPV positive women. Our reference standard will be histology. We will perform meta-analyses using Cochrane guidelines for diagnostic test accuracy. We will use the number of true positives, false negatives, true negatives and false positives from individual studies. We will use the bivariate mixed effect model to estimate sensitivity and specificity with 95% CIs; we will employ different bivariate models to estimate sensitivity and specificity at different thresholds if sufficient data per threshold. For insufficient data, the hierarchical summary receiver operating curve model will be used to calculate a summary curve across thresholds. If there is interstudy and intrastudy variation in thresholds, we will use a linear mixed effects model to calculate the optimum threshold. If few studies are available, we will simplify models by assuming no correlation between sensitivity and specificity and perform univariate, random-effects meta-analysis. We will assess the quality of studies using QUADAS-2 and QUADAS-C. Ethics and dissemination Ethical approval is not required. Results will be disseminated to academic beneficiaries, medical practitioners, patients and the public. PROSPERO registration number CRD42022299760.

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 disorder, using diagnostic modalities such as ultrasound and MRI, and rapid therapeutic approach with antibiotics, may improve maternal and neonatal outcomes.

Objective: The efficacy of prophylactic human papillomavirus (HPV) vaccines after surgical treatment for pre-invasive genital disease remains unclear. Our aim was to explore the efficacy of HPV vaccination on HPV infection risk and risk of recurrent HPV-related disease in individuals undergoing local surgical treatment for cervical or other HPV-related disease. Methods: Design: Systematic review and meta-analysis Data sources: PubMed/Medline, Scopus, Cochrane, Web of Science and ClinicalTrials.gov were screened from inception until March 2021. Inclusion criteria: Studies reporting on HPV infection risk and recurrence of HPV-related disease after local surgical treatment of pre-invasive genital disease in vaccinated individuals. Outcome measures: Primary: Recurrence risk for cervical intraepithelial neoplasia grade 2 or higher (CIN2+)(follow-up as reported by individual studies); Secondary: risk of HPV infection, other HPV-related lesions. Data extraction and risk of bias assessment: Independent and in duplicate data extraction and quality assessment using ROBINS-I and RoB-2 tools was performed for observational studies and randomised controlled trials (RCTs). Grading of Recommendations Assessment, Development and Evaluation (GRADE) was implemented for the primary outcome. Data synthesis: Observational studies and RCTs were analysed separately from post-hoc analyses of RCTs. Pooled risk ratios (RR) and 95% confidence intervals (95% CI) were calculated using a random-effects (RE) meta-analysis model. The restricted maximum likelihood was used as an estimator for heterogeneity, and the Hartung-Knapp-Sidik-Jonkman method was used to derive confidence intervals. Results: Twenty-two articles met the inclusion criteria of the review; eighteen studies also reported data from a non-vaccinated group and were included in the meta-analyses (12 observational; 2 RCTs and 4 post-hoc analyses of RCTs). The risk of CIN2+ recurrence was reduced in vaccinated when compared to non-vaccinated individuals (11 studies; 19,909 participants; RR 0.43, 95%CI 0.30 to0.60; I2=58%, τ2=0.14)(median follow-up 36 months, interquartile range 24-43.5). The effect estimate was even stronger when CIN2+ recurrence risk was assessed for HPV16/18-related disease (6 studies; 1879 participants; RR 0.26, 95%CI 0.16 to 0.43; I2=0%, τ2=0). However, the confidence in the meta-analysis for CIN2+ overall and HPV16/18-related CIN2+ as assessed by GRADE ranged from very low to moderate due to the potential presence of publication bias as well as bias and inconsistency in the included studies. The recurrence risk for CIN3 was also reduced among vaccinated patients but there was large uncertainty (3 studies; 17,757 participants; RR 0.28, 95%CI 0.01 to6.37; I2=71%, τ2=1.23). There was no strong evidence to support benefit for VIN/VaIN/AIN /genital warts recurrence, persistent and incident HPV infections, although the number of studies and participants in each outcome was low. Conclusion: HPV vaccination may reduce risk of CIN recurrence and in particular HPV16/18-related CIN in women treated with local excision. However, the GRADE assessment for quality of evidence ranged from very low to moderate; as such, the data remains inconclusive. Large-scale high-quality RCTs are required to establish level of effectiveness and cost of risk-reducing HPV vaccination in women undergoing treatment for HPV-related disease. Systematic review registration: PROSPERO (CRD42021237350).

Background: In this network meta-analysis, we compared the effectiveness and reproductive morbidity associated with various treatment methods for cervical intraepithelial neoplasia (CIN). Methods: We searched electronic databases (MEDLINE, Embase, CENTRAL) from inception until 9 March 2022 for randomised and non-randomised studies reporting on oncological and reproductive outcomes after excisional or ablative CIN treatments. The primary outcomes were any treatment failure (defined as any abnormal histology or cytology) and preterm birth (

This paper introduces the 2022 terminology for the cone dimensions after local conservative treatment for squamous intra-epithelial lesion/cervical intra-epithelial neoplasia (SIL/CIN) and early invasive cervical cancer. This is prepared by the Nomenclature Committee of the European Society of Gynaecologic Oncology (ESGO), the European Federation for Colposcopy (EFC), the International Federation of Cervical Pathology and Colposcopy (IFCPC) and the European Society of Pathology (ESP). It is recommended that the cone length is tailored to the type of transformation zone. Treatment of SIL/CIN is associated with preterm birth and this risk increases with increasing cone length. There is lack of agreement on the reporting definitions of the excised specimen dimensions intra-operatively and/or in the pathology laboratory. There is a need for a consensus terminology of the cone dimensions to make studies addressing effectiveness and safety of SIL/CIN treatment comparable and facilitate their use to tailor surveillance and antenatal management. This document summarises existing terminologies through a review of the literature. We further describe the new 2022 terminology as agreed by a group of experts from international societies in the field of cervical cancer prevention and treatment. We recommend the use of the 2022 terminology that will facilitate communication between clinicians and foster tailored treatment guidelines that balance obstetrical harm against therapeutic effectiveness.

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

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 p-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 (p < 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 (p = 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. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Purpose of Investigation: Despite the general principle that persistent high risk human papillomavirus (hr-HPV) infection may progressively cause cervical cancer (CxCa), demographic aspects may still identify groups at high risk for HPV infection and consequently for precancerous lesions. The role of demographic parameters on cervical status, the diagnostic accuracy of cytology, HPV genotyping, and their possible combinations, were investigated in this study. Materials and Methods: 11,072 women from diverse locations across Greece participated in the study. Liquid Based Cytologic (LBC) assessment was followed, when necessary, by HPV-genotyping and histologic confirmation. Demographic characteristics were also assessed. Results: Life style parameters such as age, number of sexual partners, condom use, parity and marital status, education level, and combination of smoking/condom use, were significant factors for CIN2+ lesions (p < 0.05). For LSIL+ detection, cytology had maximum sensitivity: 96.90%, HPV-typing: 72.55% and co-testing: 98.97%, for HSIL+ detection: 98.49%, 92.22%, and 99.55% respectively. Conclusions: There are notable relationships between lifestyle, demographic details, and cervical status. Despite the differences in sensitivity and specificity levels, co-testing might offer some marginal improvement in the detection of particular pre-cancerous conditions. ©2020 Mnimatidis et al.

Background: Infection by HPV oncogenic subtypes is the causative agent of half a million cancer cases in developed countries every year. The objective of the present study was to assess: the knowledge and beliefs of young Greeks about HPV infection and potential factors that discourage them from HPV vaccination. Materials and Methods: The present group consisted of 825 individuals, 18-35-years-old, who voluntarily completed some questionnaires. Results: The attitude and consequent decision of women, considering HPV vaccination is associated with general vaccination attitude, mothers' beliefs, parents' educational level, family income, knowledge about HPV, the doctor's attitude, and individual's health beliefs. Conclusion: In Greece, as well as in other countries where HPV vaccination is neither a mandatory nor a school-based program, increased education of physicians and parents would substantially enhance HPV vaccination acceptance. Intervention strategies should focus more on providing adequate and reliable information to eliminate any doubts on HPV vaccine's safety and efficacy.