Microbial signatures and continuum in endometrial cancer and benign patients.

BACKGROUND: Endometrial cancer is a multifactorial disease with inflammatory, metabolic and potentially microbial cues involved in disease pathogenesis. The endometrial cancer microbiome has been poorly characterised so far and studies have often overestimated bacterial biomass due to lack of integration of appropriate contamination controls. There is also a scarcity of evidence on the functionality of microbial microenvironments in endometrial cancer. This work addresses that knowledge gap by interrogating the genuine, contamination-free microbial signatures in the female genital tract and rectum of women with endometrial cancer and the mechanistic role of microbiome on carcinogenic processes. RESULTS: Here we sampled different regions of the reproductive tract (vagina, cervix, endometrium, fallopian tubes and ovaries) and rectum of 61 patients (37 endometrial cancer; 24 benign controls). We performed 16S rRNA gene sequencing of the V1-V2 hypervariable regions and qPCR of the 16S rRNA gene to qualitatively and quantitatively assess microbial communities and used 3D benign and endometrial cancer organoids to evaluate the effect of microbial products of L. crispatus, which was found depleted in endometrial cancer patients following primary analysis, on endometrial cell proliferation and inflammation. We found that the upper genital tract of a subset of women with and without endometrial cancer harbour microbiota quantitatively and compositionally distinguishable from background contaminants. Endometrial cancer was associated with reduced cervicovaginal and rectal bacterial load together with depletion of Lactobacillus species relative abundance, including L. crispatus, increased bacterial diversity and enrichment of Porphyromonas, Prevotella, Peptoniphilus and Anaerococcus in the lower genital tract and endometrium. Treatment of benign and malignant endometrial organoids with L. crispatus conditioned media exerted an anti-proliferative effect at high concentrations but had minimal impact on cytokine and chemokine profiles. CONCLUSIONS: Our findings provide evidence that the upper female reproductive tract of some women contains detectable levels of bacteria, the composition of which is associated with endometrial cancer. Whether this is a cause or consequence of cancer pathophysiology and what is the functional significance of this finding remain to be elucidated to guide future screening tools and microbiome-based therapeutics. Video Abstract.

Cytokines in Bladder Pain Syndrome: A Review of the Literature.

INTRODUCTION AND HYPOTHESIS: Bladder pain syndrome (BPS) is poorly understood with both the aetiology and pathophysiology being unknown. Symptoms overlap with other disorders, such as overactive bladder (OAB) and chronic pelvic pain disorders such as endometriosis, making a consensus on how to diagnosis and manage patients challenging. The development of biomarkers for BPS may be the key to understanding more about its pathophysiology, as well as aiding diagnosis, subclassification, and discovering new drug targets for its management. As inflammation is widely understood to hold a central role in BPS, the evaluation of cytokines has gained interest. This article summarises the current literature and understanding of urinary, serum, and bladder tissue cytokines found elevated in patients with bladder pain syndrome. METHODS: literature search using Pub Med with the keywords "bladder pain syndrome", "painful bladder syndrome", "bladder pain", "Interstitial cystitis" AND "cytokines" or "inflammation". This study was except from institutional approval. RESULTS: Thirty-six cytokines have been identified as being statistically significantly elevated in either the serum, urine, or bladder tissue of patients with bladder pain syndrome in the 22 studies identified in this review of the literature. These cytokines include those from the interleukin group (n = 14), the CXC chemokine group (n = 5), and the C-C chemokine group (n = 7). CONCLUSIONS: CXCL-1, CXCL-8, CXCL-9, CXCL-10, CXCL-11 from the CXC chemokine group, and CCL2, CCL4, CCL5, CCL7, and CCL11 from the C-C chemokine group have been found to be significantly elevated in patients with bladder pain in the literature. Many of these analytes also have supporting evidence for their roles in bladder pain from animal models and studies in other chronic inflammatory conditions. It is likely that a single cytokine will not serve as an adequate biomarker of disease in bladder pain syndrome for either diagnosis or disease severity. Instead, panels of inflammatory mediators may reveal more about the different pathways of inflammation leading to similar presentations of bladder pain in patients.

Treatment methods for cervical intraepithelial neoplasia in England: A cost-effectiveness analysis.

OBJECTIVE: To compare the cost-effectiveness of different treatments for cervical intraepithelial neoplasia (CIN). DESIGN: A cost-effectiveness analysis based on data available in the literature and expert opinion. SETTING: England. POPULATION: Women treated for CIN. METHODS: We developed a decision-analytic model to simulate the clinical course of 1000 women who received local treatment for CIN and were followed up for 10 years after treatment. In the model we considered surgical complications as well as oncological and reproductive outcomes over the 10-year period. The costs calculated were those incurred by the National Health Service (NHS) of England. MAIN OUTCOME MEASURES: Cost per one CIN2+ recurrence averted (oncological outcome); cost per one preterm birth averted (reproductive outcome); overall cost per one adverse oncological or reproductive outcome averted. RESULTS: For young women of reproductive age, large loop excision of the transformation zone (LLETZ) was the most cost-effective treatment overall at all willingness-to-pay thresholds. For postmenopausal women, LLETZ remained the most cost-effective treatment up to a threshold of £31,500, but laser conisation became the most cost-effective treatment above that threshold. CONCLUSIONS: LLETZ is the most cost-effective treatment for both younger and older women. However, for older women, more radical excision with laser conisation could also be considered if the NHS is willing to spend more than £31,500 to avert one CIN2+ recurrence.

Digital consent in gynecology: an evaluation of patient experience.

INTRODUCTION: The surgical consent process is a crucial discussion between patient and surgeon, which is predominantly documented utilizing hand-written forms. The exchange of individualized information allows the patient to make a truly informed decision. Digital consent (also known as electronic consent or e-consent) has been shown to improve accuracy of information provided without increasing the time taken to consent patients. We aimed to evaluate patient experience and effectiveness of digital consent in a gynecology department in a tertiary London Teaching Hospital. METHODS: A questionnaire was designed and completed by 100 patients undergoing gynecological surgery: 50 consented using paper and 50 consented digitally. The questionnaire included 8 statements, with five possible answers to select, ranging from strongly agree to strongly disagree, on a standard five-point Likert Scale. Patients were all female and categorized into age groups (deciles) and asked whether consent was taken digitally or on paper. Data were collected between January and July 2021. RESULTS: Most responses were positive with 87% (694/800) of responses to the questions being either strongly agree or agree. Patients who were consented using paper selected 'strongly agree' 43.5% (174/400) of the time in comparison to 64.8% (259/400) of the time when they were consented digitally. The majority, 86% (43/50), of digitally consented patients received a copy of the consent form in comparison to 18% (9/50) of those consented using paper. On average, the patients consented digitally were older than their paper-consented counterparts (49-58 and 59-68 respectively). The mean scores for the questions relating to the ease of reading the form, ease of understanding the form, understanding of the potential complications, and overall satisfaction were higher in those digitally consented (p < 0.05). DISCUSSION: Overall, patients were satisfied with both methods of consent. However, individuals who were consented digitally reported higher levels of satisfaction throughout the consent process, compared to paper consent. These data suggest that digital consent is an acceptable alternative to paper consent for patients and facilitates adherence to national consent guidance, which stipulates patients should be given the information they request.

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.

Female genital tract (FGT) microbiota has been associated with the development of gynaecological cancers. Thus, the possibility of whether manipulation of the FGT microbiota can help in the prevention of disease should be investigated. Various prebiotics, probiotics, and other non-clinician prescribed agents have been reported to have therapeutic effects in cervical disease. Numerous studies have reported an association between human papillomavirus infection and subsequent cervical dysplasia and a decrease in the abundance of Lactobacillus species. A continuum of microbiota composition is observed from the vagina to the upper parts of the FGT, but no evidence suggests that manipulation of the vaginal microbiota can help to modify the composition of other FGT compartments. Although prebiotics and probiotics have been reported to be beneficial, the studies are small and of varying design, and high-quality evidence to support their use is lacking. Currently, no studies have examined these therapeutics in other gynaecological malignancies. Thus, recommendation of probiotics, prebiotics, or other over-the-counter supplements for the prevention of gynaecological cancers warrants larger, well designed studies.

Preventing cervical cancer: what are the risks and benefits of different treatments?

The studyKyrgiou M, Athanasiou A, Cieslak-Jones D. Comparative effectiveness and risk of preterm birth of local treatments for cervical intraepithelial neoplasia and stage IA1 cervical cancer: a systematic review and network meta-analysis. Lancet Oncol 2022;23:1097-108.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/prevention-of-cervical-cancer-what-are-the-risks-and-benefits-of-different-treatments/.

Risk factors for human papillomavirus infection, cervical intraepithelial neoplasia and cervical cancer: an umbrella review and follow-up Mendelian randomisation studies.

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

Protocol for a systematic review and meta-analysis of the diagnostic test accuracy of host and HPV DNA methylation in cervical cancer screening and management.

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.

Diabetes and anti-diabetic interventions and the risk of gynaecological and obstetric morbidity: an umbrella review of the literature.

BACKGROUND: Diabetes has reached epidemic proportions in recent years with serious health ramifications. The aim of this study was to evaluate the strength and validity of associations between diabetes and anti-diabetic interventions and the risk of any type of gynaecological or obstetric conditions. METHODS: Design: Umbrella review of systematic reviews and meta-analyses. DATA SOURCES: PubMed, Medline, Embase, Cochrane Database of Systematic Reviews, manual screening of references. ELIGIBILITY CRITERIA: Systematic reviews and meta-analyses of observational and interventional studies investigating the relationship between diabetes and anti-diabetic interventions with gynaecological or obstetric outcomes. Meta-analyses that did not include complete data from individual studies, such as relative risk, 95% confidence intervals, number of cases/controls, or total population were excluded. DATA ANALYSIS: The evidence from meta-analyses of observational studies was graded as strong, highly suggestive, suggestive or weak according to criteria comprising the random effects estimate of meta-analyses and their largest study, the number of cases, 95% prediction intervals, I2 heterogeneity index between studies, excess significance bias, small study effect and sensitivity analysis using credibility ceilings. Interventional meta-analyses of randomised controlled trials were assessed separately based on the statistical significance of reported associations, the risk of bias and quality of evidence (GRADE) of included meta-analyses. RESULTS: A total of 117 meta-analyses of observational cohort studies and 200 meta-analyses of randomised clinical trials that evaluated 317 outcomes were included. Strong or highly suggestive evidence only supported a positive association between gestational diabetes and caesarean section, large for gestational age babies, major congenital malformations and heart defects and an inverse relationship between metformin use and ovarian cancer incidence. Only a fifth of the randomised controlled trials investigating the effect of anti-diabetic interventions on women's health reached statistical significance and highlighted metformin as a more effective agent than insulin on risk reduction of adverse obstetric outcomes in both gestational and pre-gestational diabetes. CONCLUSIONS: Gestational diabetes appears to be strongly associated with a high risk of caesarean section and large for gestational age babies. Weaker associations were demonstrated between diabetes and anti-diabetic interventions with other obstetric and gynaecological outcomes. TRIAL REGISTRATION: Open Science Framework (OSF) (Registration https://doi.org/10.17605/OSF.IO/9G6AB ).

Primary Melanoma of the Cervix Uteri: A Systematic Review and Meta-Analysis of the Reported Cases.

Primary malignant melanoma (MM) of the cervix uteri is a rare and aggressive malignancy of the female reproductive tract. Considering that clinical data on this cancer are scarce, we aimed to comprehensively examine the currently available literature and provide an overview of the reported cases of cervical MM focusing on the clinical characteristics, diagnosis and therapeutic management. We conducted a systematic review of the literature by screening three electronic databases until June 2022. The critical appraisal checklist provided by the Joanna Briggs Institute was employed to evaluate the overall quality of the studies. We included 96 reports, which comprised 137 patients diagnosed with MM of the cervix. The mean age of the patients was 56.5 (median: 58, age range: 33-88). Data regarding menopausal status were provided for 98 patients with 15 being premenopausal and 83 being postmenopausal. The most common presenting symptom was vaginal bleeding (83%, 100/121). Biopsy (either excisional or punch biopsy) was used as the first diagnostic modality in most of the patients (67%, 64/95), followed by cytology (18%, 17/95). In 74 cases, the FIGO staging system for cervical cancer was used with the most common stage being FIGO stage I (38%, 28/74), followed by FIGO stage II (36%, 27/74), FIGO stage III (19%, 14/74) and FIGO stage IV (7%, 5/74). Most of the patients were managed surgically (90%, 119/131) with a hysterectomy (either radical or total), and a salpingo-oophorectomy with/without lymphadenectomy was the most common approach utilized (40%, 48/119). The data of clinical outcomes were provided for 105 patients, of whom 61 died (58%, 61/105) and 44 survived (42%, 44/105). Knowledge regarding the rare occurrence of MM in the cervix and the increased awareness of clinicians can prevent clinical misdiagnosis and ultimately improve further the clinical outcomes of patients developing this rare malignancy.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) Consensus Statement on the Management of Vaginal Intraepithelial Neoplasia.

ABSTRACT: The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vaginal intraepithelial neoplasia (VaIN). The management of VaIN varies according to the grade of the lesion: VaIN 1 (low grade vaginal squamous intraepithelial lesions (SIL)) can be subjected to follow-up, while VaIN 2-3 (high-grade vaginal SIL) should be treated. Treatment needs individualization according to the patient's characteristics, disease extension and previous therapeutic procedures. Surgical excision is the mainstay of treatment and should be performed if invasion cannot be excluded. Total vaginectomy is used only in highly selected cases of extensive and persistent disease. Carbon dioxide (CO2) laser may be used as both an ablation method and an excisional one. Reported cure rates after laser excision and laser ablation are similar. Topical agents are useful for persistent, multifocal lesions or for patients who cannot undergo surgical treatment. Imiquimod was associated with the lowest recurrence rate, highest human papillomavirus (HPV) clearance, and can be considered the best topical approach. Trichloroacetic acid and 5-fluorouracil are historical options and should be discouraged. For VaIN after hysterectomy for cervical intraepithelial neoplasia (CIN) 3, laser vaporization and topical agents are not the best options, since they cannot reach epithelium buried in the vaginal scar. In these cases surgical options are preferable. Brachytherapy has a high overall success rate but due to late side effects should be reserved for poor surgical candidates, having multifocal disease, and with failed prior treatments. VaIN tends to recur and ensuring patient adherence to close follow-up visits is of the utmost importance. The first evaluation should be performed at 6 months with cytology and an HPV test during 2 years and annually thereafter. The implementation of vaccination against HPV infection is expected to contribute to the prevention of VaIN and thus cancer of the vagina. The effects of treatment can have an impact on quality of life and result in psychological and psychosexual issues which should be addressed. Patients with VaIN need clear and up-to-date information on a range of treatment options including risks and benefits, as well as the need for follow-up and the risk of recurrence.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) consensus statement on the management of vaginal intraepithelial neoplasia.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vaginal intraepithelial neoplasia (VaIN). The management of VaIN varies according to the grade of the lesion: VaIN 1 (low grade vaginal squamous intraepithelial lesions (SIL)) can be subjected to follow-up, while VaIN 2-3 (high-grade vaginal SIL) should be treated. Treatment needs individualization according to the patient's characteristics, disease extension and previous therapeutic procedures. Surgical excision is the mainstay of treatment and should be performed if invasion cannot be excluded. Total vaginectomy is used only in highly selected cases of extensive and persistent disease. Carbon dioxide (CO2) laser may be used as both an ablation method and an excisional one. Reported cure rates after laser excision and laser ablation are similar. Topical agents are useful for persistent, multifocal lesions or for patients who cannot undergo surgical treatment. Imiquimod was associated with the lowest recurrence rate, highest human papillomavirus (HPV) clearance, and can be considered the best topical approach. Trichloroacetic acid and 5-fluorouracil are historical options and should be discouraged. For VaIN after hysterectomy for cervical intraepithelial neoplasia (CIN) 3, laser vaporization and topical agents are not the best options, since they cannot reach epithelium buried in the vaginal scar. In these cases surgical options are preferable. Brachytherapy has a high overall success rate but due to late side effects should be reserved for poor surgical candidates, having multifocal disease, and with failed prior treatments. VaIN tends to recur and ensuring patient adherence to close follow-up visits is of the utmost importance. The first evaluation should be performed at 6 months with cytology and an HPV test during 2 years and annually thereafter. The implementation of vaccination against HPV infection is expected to contribute to the prevention of VaIN and thus cancer of the vagina. The effects of treatment can have an impact on quality of life and result in psychological and psychosexual issues which should be addressed. Patients with VaIN need clear and up-to-date information on a range of treatment options including risks and benefits, as well as the need for follow-up and the risk of recurrence.

Cervical High-Grade Squamous Intraepithelial Lesion Burden and Standard of Care Treatment Effectiveness and Safety in the United States, 2008-2018: The EACH-WOMAN Project.

OBJECTIVE: Management of cervical high-grade squamous intraepithelial lesions (HSILs), the immediate precursor of cervical cancer, consists largely of surgical treatment for women at higher risk for progression to cancer. The authors' objective was to describe the occurrence of cervical HSIL in the United States and various outcomes for women who received surgical treatment. METHODS: From a US commercial health insurer, a cohort of adult women with cervical HSIL diagnoses receiving surgical treatment within 3 months of diagnosis between January 2008 and September 2018 was identified. This cohort was followed for several outcomes, including cervical HSIL recurrence, human papillomavirus clearance, preterm birth, infection, and bleeding. RESULTS: The incidence rate of cervical HSIL declined from 2.34 (95% CI = 2.30-2.39) cases per 1,000 person-years in 2008 to 1.39 (95% CI = 1.35-1.43) cases per 1,000 person-years in 2014, remaining near that level through 2018. Among 65,527 women with cervical HSIL, 47,067 (72%) received surgical treatment within 3 months of diagnosis. Among the women receiving surgical treatment, cervical HSIL recurred in 6% of surgically treated women, whereas 45% of surgically treated women underwent subsequent virological testing that indicated human papillomavirus clearance. Preterm birth was observed in 5.9% by 5 years follow-up and bleeding and infection each at 2.2% by 7 days follow-up. CONCLUSIONS: From 2008 through 2018, the incidence of diagnosed cervical HSIL decreased for several years before stabilizing. Surgical treatment of HSIL may be beneficial in removing the precancerous lesion, but cervical HSIL may recur, and the surgery is associated with complications including preterm birth, infection, and bleeding.

Minimally Invasive Compared With Open Surgery in High-Risk Endometrial Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: To compare outcomes between minimally invasive surgery and open surgery in patients with high-risk endometrial cancer. DATA SOURCES: A cohort study of all patients who underwent surgery for high-risk endometrial cancer between 1999 and 2016 at Mayo Clinic (Rochester, Minnesota) and a literature search of MEDLINE, EMBASE, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, and Scopus of all published studies until December 2020. METHODS OF STUDY SELECTION: The systematic review identified 2,332 patients (14 studies, all retrospective except a subanalysis of a randomized comparison) and the cohort study identified 542 additional patients. Articles were included if reporting original data on overall survival and disease-free survival among patients with high-risk endometrial cancer, defined as International Federation of Gynecology and Obstetrics grade 3 endometrioid, serous, clear cell, mixed histology, or uterine carcinosarcoma. Studies that did not report at least one of the main outcomes, those in which one surgical technique (robotic or laparoscopic surgery) was missing in the comparison analysis with open surgery, and case reports were excluded. Additional data were extracted from a retrospective cohort of patients from Mayo. A random-effect model was used for meta-analysis. TABULATION, INTEGRATION, AND RESULTS: This systematic review and meta-analysis was registered in PROSPERO. Literature search and data extraction were performed independently by two reviewers, as well as quality assessment using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology, and the Newcastle-Ottawa Scale. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. Meta-analysis showed that disease-free survival and overall survival in patients with high-risk endometrial cancer who underwent minimally invasive surgery were not statistically different from those of patients who underwent open abdominal surgery (relative risk [RR] 0.93, 95% CI 0.82-1.05, I2 20%, P=.23; and RR 0.92, 95% CI 0.77-1.11, I2 31%, P=.12, respectively). Subgroup analysis by stage (early vs advanced) did not identify a difference between surgical approaches. CONCLUSION: Minimally invasive surgery and open surgery had similar disease-free survival and overall survival in patients with high-risk endometrial cancer. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021275535.

High Prevalence of HPV 51 in an Unvaccinated Population and Implications for HPV Vaccines.

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

Overtreatment rate after immediate local excision of suspected cervical intraepithelial neoplasia: A prospective cohort study.

OBJECTIVE: The gold standard of cervical intraepithelial neoplasia (CIN) treatment is large loop excision of the transformation zone (LLETZ) after histopathological diagnosis from punch biopsies. In addition, treatment may be appropriate at initial colposcopy. Our objective was to study the applicability of immediate treatment strategy according to clinical parameters. METHODS: We conducted a prospective cohort study among patients referred to colposcopy at Helsinki University Hospital, Finland, between January 2014, and September 2018 (ISRCTN10933736). Patients treated with LLETZ, either after biopsies or immediately at initial colposcopy, were included. The main outcome measure was overtreatment (OT) rate defined as normal or low-grade histopathological findings in LLETZ specimen within both treatment groups. RESULTS: A total of 572 patients treated with LLETZ were included: 360 treated after biopsies and 212 treated immediately at initial colposcopy. When LLETZ was performed immediately after high-grade referral cytology and with colposcopic impression of high-grade disease, the overtreatment (OT) rate was 10.0% (95% CI 9.10 to 17.2), whereas when LLETZ was done after biopsy-confirmed high-grade lesions, the OT rate was 18.9% (95% CI 14.7 to 23.7), resulting in risk difference (RD) -8.91% (95% CI -16.0 to -1.82). Among HPV16/18 positive patients the OT rate was 8.22% (95% CI 3.08 to 17.0) for immediate treatment, resulting in RD of -10.7% (95% CI -18.3 to -3.04) compared to LLETZ after biopsies. CONCLUSIONS: Immediate LLETZ does not result in overtreatment when applied on selected cases, especially after high-grade referral cytology and when high-grade lesion is also colposcopically suspected.