Fragmentomics features of ovarian cancer.

Ovarian cancer (OC) is a major cause of cancer mortality in women worldwide. Due to the occult onset of OC, its nonspecific clinical symptoms in the early phase, and a lack of effective early diagnostic tools, most OC patients are diagnosed at an advanced stage. In this study, shallow whole-genome sequencing was utilized to characterize fragmentomics features of circulating tumor DNA (ctDNA) in OC patients. By applying a machine learning model, multiclass fragmentomics data achieved a mean area under the curve (AUC) of 0.97 (95% CI 0.962-0.976) for diagnosing OC. OC scores derived from this model strongly correlated with the disease stage. Further comparative analysis of OC scores illustrated that the fragmentomics-based technology provided additional clinical benefits over the traditional serum biomarkers cancer antigen 125 (CA125) and the Risk of Ovarian Malignancy Algorithm (ROMA) index. In conclusion, fragmentomics features in ctDNA are potential biomarkers for the accurate diagnosis of OC.

Identifying Serum Small Extracellular Vesicle MicroRNA as a Noninvasive Diagnostic and Prognostic Biomarker for Ovarian Cancer.

There remains a lack of effective and noninvasive methods for the diagnosis and prognosis prediction of epithelial ovarian carcinoma (EOC). Here, we investigated the possibility of serum-derived small extracellular vesicle (sEV) microRNAs (miRNAs) as potential biomarkers for distinguishing between benign and malignant adnexal masses and predicting the prognosis of EOC patients. A serum sEV miRNA model for identifying the EOC (sEVmiR-EOC) was successfully established in the training cohort. Furthermore, the sEVmiR-EOC model was confirmed in the testing cohort and validation cohort, demonstrating robust diagnostic accuracy. The sEVmiR-EOC model showed better performance than carbohydrate antigen 125 (CA125) in discriminating patients with stage I EOC from benign patients. Using EOC samples and follow-up data, we identified miR-141-3p and miR-200c-3p as potential prognostic predictors. Finally, we confirmed the change of the sEVmiR-EOC RiskScore between the preoperative and postoperative samples and found that the sEVmiR-EOC model could predict the prognosis of EOC patients.

The application of risk models based on machine learning to predict endometriosis-associated ovarian cancer in patients with endometriosis.

INTRODUCTION: There is currently no satisfactory model for predicting malignant transformation of endometriosis. The aim of this study was to construct and evaluate a risk model incorporating noninvasive clinical parameters to predict endometriosis-associated ovarian cancer (EAOC) in patients with endometriosis. MATERIAL AND METHODS: We enrolled 6809 patients with endometriosis confirmed by pathology, and randomly allocated them to training (n = 4766) and testing cohorts (n = 2043). The proportion of patients with EAOC in each cohort was similar. We extracted a total of 94 demographic and clinicopathologic features from the medical records using natural language processing. We used a machine learning method - gradient-boosting decision tree - to construct a predictive model for EAOC and to evaluate the accuracy of the model. We also constructed a multivariate logistic regression model inclusive of the EAOC-associated risk factors using a back stepwise procedure. Then we compared the performance of the two risk-predicting models using DeLong's test. RESULTS: The occurrence of EAOC was 1.84% in this study. The logistic regression model comprised 10 selected features and demonstrated good discrimination in the testing cohort, with an area under the curve (AUC) of 0.891 (95% confidence interval [CI] 0.821-0.960), sensitivity of 88.9%, and specificity of 76.7%. The risk model based on machine learning had an AUC of 0.942 (95% CI 0.914-0.969), sensitivity of 86.8%, and specificity of 86.7%. The machine learning-based risk model performed better than the logistic regression model in DeLong's test (p = 0.036). Furthermore, in a prospective dataset, the machine learning-based risk model had an AUC of 0.8758, a sensitivity of 94.4%, and a specificity of 73.8%. CONCLUSIONS: The machine learning-based risk model was constructed to predict EAOC and had high sensitivity and specificity. This model could be of considerable use in helping reduce medical costs and designing follow-up schedules.

Research of the Potential Vaginal Microbiome Biomarkers for High-Grade Squamous Intraepithelial Lesion.

Vaginal microbiome may have a role in HPV infection and cervical neoplasm. To explore potential vaginal microbiome biomarkers for high-grade squamous intraepithelial lesion (HSIL), and to find the best scheme to facilitate the current cervical cancer screening strategy. This study enrolled 272 women, including 83 confirmed with HSIL, 86 with HPV infection but without cervical neoplasm, and 103 without HPV infection as controls. Vaginal microbiome composition was determined by sequencing of barcoded 16S rDNA gene fragments (V4) on Illumina HiSeq2500. The relative increasing abundance of Stenotrophomonas, Streptococcus, and Pseudomonas, and a concomitant paucity of Dialister, unidentified Prevotellaceae, Faecalibacterium, Bifidobacterium, and Bacteroides, were related with HSIL, which can be used to predict the development of HISL in high-risk HPV infected patients. The relative abundance of Stenotrophomonas being over 0.0090387%, or Faecalibacterium being under 0.01420015%, or Bifidobacterium being under 0.0116183% maybe a good predictor for HSIL for those infected with HPV 16 and/or 18. The relative abundance of Stenotrophomonas being over 0.01549105%, or Streptococcus being over 0.48409585%, or Bacteroides being under 0.0296912% maybe a good predictor for HSIL for those infected with the 12 other high-risk types of HPV with concurrent abnormal TCT results. This study revealed that potential vaginal microbiome biomarkers may relate to HSIL, and can facilitate the cervical cancer screening.

The role of the vaginal microbiome in distinguishing female chronic pelvic pain caused by endometriosis/adenomyosis.

BACKGROUND: This study aimed to investigate the specific vaginal microbiome in the differential diagnosis of endometriosis/adenomyosis (EM/AM)-associated chronic pelvic pain (CPP) from other types of CPP, and to explore the role of the vaginal microbiome in the mechanism of EM/AM-associated CPP. METHODS: We recruited 37 women with EM/AM-associated CPP, 25 women with chronic pelvic pain syndrome (CPPS) without EM/AM, and 66 women without CPPS into our study. All of the participants were free from human papillomavirus (HPV) infection. Sequencing of barcoded 16S rRNA gene fragments (V4) was used to determine the vaginal microbiome composition on the Illumina HiSeq2500 System. Taxonomic and functional bioinformatics analyses were performed using t-test, linear discriminant analysis effect size (LEfSe), MetaStat, and PICRUSt algorithms. RESULTS: At the species level, EM/AM-associated CPP was found to be associated with a predominance of Clostridium butyricum, Clostridium disporicum, Alloscardovia omnicolens, and Veillonella montpellierensis, and a concomitant paucity of Lactobacillus jensenii, Lactobacillus reuteri, and Lactobacillus iners. When the relative abundance of Clostridium disporicum was over 0.001105% and that of Lactobacillus reuteri was under 0.1911349%, the differential diagnostic sensitivity and specificity were 81.08% and 52.0%, respectively. When serum CA125 was combined, the sensitivity increased to 89.19%, but the specificity remained at 52.0%. The PICRUSt results identified 7 differentially regulated pathways within the 3 groups that may be of relevance. CONCLUSIONS: Compared to that of CPPS patients without EM/AM and women without CPPS, the vaginal microbiome of patients with EM/AM-associated CPP shows significantly higher alpha (phylogenetic) diversity, as well as higher counts of Clostridium butyricum, Clostridium disporicum, Alloscardovia omnicolens, and Veillonella montpellierensis. These differences in the vaginal microbiome may interfere with local functional pathways, which could provide a direction for innovative metabolite-specific targeted treatment. The combination of vaginal biomarkers and serum CA125 may provide an original method to differentiate EM/AM-associated CPP.

Selection of Treatment Regimens for Recurrent Cervical Cancer.

OBJECTIVE: The selection of individualized treatment for recurrent cervical cancer is challenging. This study aimed to investigate the impact of various therapies on survival outcomes after recurrence. METHODS: Eligible patients were diagnosed with recurrent cervical cancer between March 2012 and April 2018. Postrecurrence progression-free survival (PFS) and overall survival (OS) were investigated in the whole cohort and in subgroups, categorized by recurrence site and prior radiotherapy history, using a multivariate model that incorporated treatment for primary and recurrent tumors, histological pathology, and FIGO staging. RESULTS: Two hundred and sixty recurrent cervical cancer patients were included. As of March 1, 2020, the median postrecurrence PFS and OS were 7.0 (range 0-94) and 24.0 (1.8-149.1) months, respectively. In a multivariate model measured by PFS, radiotherapy was superior to other therapies for the whole cohort (p=0.029) and recurrence only within the pelvic cavity (p=0.005), but the advantages of radiotherapy disappeared in patients with a history of radiotherapy (p values >0.05). For recurrence only beyond the pelvic cavity, combination therapy resulted in improved PFS (p=0.028). For recurrence both within and beyond the pelvic cavity, no therapy regimen provided additional PFS benefits (p values >0.05). Radiotherapy and combination therapy were also associated with improved postrecurrence OS for recurrence within the pelvic cavity (p=0.034) and only beyond the pelvic cavity (p=0.017), respectively. CONCLUSIONS: In cervical cancer patients, postrecurrence radiotherapy can improve PFS and OS for patients with recurrence within the pelvic cavity and without prior radiotherapy. For recurrence beyond the pelvic cavity or cases with a history of radiotherapy, combination or individualized therapy may provide potential survival benefits.

Genomic alterations caused by HPV integration in a cohort of Chinese endocervical adenocarcinomas.

The association between human papillomavirus (HPV) integration and relevant genomic changes in uterine cervical adenocarcinoma is poorly understood. This study is to depict the genomic mutational landscape in a cohort of 20 patients. HPV+ and HPV- groups were defined as patients with and without HPV integration in the host genome. The genetic changes between these two groups were described and compared by whole-genome sequencing (WGS) and whole-exome sequencing (WES). WGS identified 2916 copy number variations and 743 structural variations. WES identified 6113 somatic mutations, with a mutational burden of 2.4 mutations/Mb. Six genes were predicted as driver genes: PIK3CA, KRAS, TRAPPC12, NDN, GOLGA6L4 and BAIAP3. PIK3CA, NDN, GOLGA6L4, and BAIAP3 were recognized as significantly mutated genes (SMGs). HPV was detected in 95% (19/20) of patients with cervical adenocarcinoma, 7 of whom (36.8%) had HPV integration (HPV+ group). In total, 1036 genes with somatic mutations were confirmed in the HPV+ group, while 289 genes with somatic mutations were confirmed in the group without HPV integration (HPV- group); only 2.1% were shared between the two groups. In the HPV+ group, GOLGA6L4 and BAIAP3 were confirmed as SMGs, while PIK3CA, NDN, KRAS, FUT1, and GOLGA6L64 were identified in the HPV- group. ZDHHC3, PKD1P1, and TGIF2 showed copy number amplifications after HPV integration. In addition, the HPV+ group had significantly more neoantigens. HPV integration rather than HPV infection results in different genomic changes in cervical adenocarcinoma.

Adjuvant therapy in conservative surgery for adenomyosis.

OBJECTIVE: To investigate the significance of perioperative levonorgestrel-releasing intrauterine system (LNG-IUS) and/or gonadotropin-releasing hormone agonists (GnRHa) as adjuvant therapy in preventing recurrences or progression of diseases. METHODS: Medical records were collected from patients diagnosed with adenomyosis who underwent uterus-sparing surgeries from March 1, 2012 to December 31, 2018. The associations of perioperative adjuvant therapy with recurrence of disease and symptoms were analyzed with the Kaplan-Meier method and proportional hazards models with hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: A total of 322 eligible patients were included, of whom 173 (58.1%) received perioperative adjuvant therapy. Perioperative adjuvant therapy (HR 0.44, 95% CI 0.22-0.91, P = 0.022) and perioperative GnRHa therapy (HR 0.48, 95% CI 0.24-0.99, P = 0.042) significantly reduced disease recurrence. No patient using perioperative LNG-IUS therapy experienced recurrence. In the multivariate analysis, increased age (>35 years at surgery) was the only risk factor for disease recurrence (HR 2.35, 95% CI 1.01-5.45, P = 0.047). CONCLUSION: Perioperative adjuvant therapy with GnRHa and/or the LNG-IUS can significantly reduce disease recurrence or progression for adenomyosis patients undergoing uterus-sparing surgery. Older patients are more likely to experience disease recurrence.

A prospective, open-label, single-arm study to evaluate the efficacy of dydrogesterone in the treatment of endometrial polyps.

OBJECT: To evaluate the efficacy of dydrogesterone for the treatment of premenopausal patients with endometrial polyps (EPs). METHODS: A single-center, open-label, prospective, single-arm clinical treatment trial was conducted in patients of reproductive age with EP(s). Patients were prescribed dydrogesterone from day 15 to day 24 of the menstrual cycle over a period of 3 months. At the 3-month follow-up, the efficacy of dydrogesterone was evaluated based on changes in self-report symptoms and ultrasonographic characteristics. The predictive factors of efficacy as well as the predictive value of the significant factors were also assessed. RESULTS: A total of 60 patients were included. Improvements in both symptoms and ultrasound findings occurred in 31 patients, achieving an efficacy rate of 51.67%. Of 41 patients with clinical presentations, 39 (95.1%) reported improvements in symptoms. In terms of ultrasound findings, 33 (55%) of patients demonstrated improvements. Significant decreases were observed in the mean endometrial thickness (1.17 ± 0.33 cm vs 0.90 ± 0.35 cm, p < .001) and polyp size (1.10 ± 0.34 cm vs 0.74 ± 0.65 cm, p = .001) after the application of dydrogesterone. Age (p = .006), polyp size (p = .006), and blood flow within polyps (p = .035) were significant predictors of dydrogesterone efficacy. These factors, when combined, demonstrated a good predictive value ([area under the curve (AUC)=0.81]). CONCLUSION: Dydrogesterone is effective in the management of EPs in premenopausal patients. Age, polyp size and blood flow should be taken into consideration when prescribing dydrogesterone for this population of women.

Diagnostic Strategies for Recurrent Cervical Cancer: A Cohort Study.

OBJECTIVE: The effectiveness of various strategies for the post-treatment monitoring of cervical cancer is unclear. This pilot study was conducted to explore recurrence patterns in and diagnostic strategies for patients with uterine cervical cancer who were meticulously followed using a customized monitoring plan. METHODS: The epidemiological and clinical data of patients with recurrent cervical cancer treated from March 2012 to April 2018 at a tertiary teaching hospital were retrospectively collected. The diagnostic methods and their reliability were compared across patients with various clinicopathological characteristics and were associated with survival outcomes. RESULTS: Two hundred sixty-four patients with recurrent cervical cancer were included in the study, among which recurrence occurred in the first three years after the last primary treatment in 214 patients (81.06%). Half of the recurrence events (50.76%) occurred only within the pelvic cavity, and most lesions (78.41%) were multiple in nature. Among all recurrent cases, approximately half were diagnosed based on clinical manifestations (n=117, 44.32%), followed by imaging examinations (n=76, 28.79%), serum tumor markers (n=34, 12.88%), physical examinations (n=33, 12.50%) and cervical cytology with or without high-risk human papillomavirus (hrHPV) testing (n=4, 1.52%). The reliability of the diagnostic methods was affected by the stage (p<0.001), primary treatment regimen (p=0.001), disease-free survival (p=0.022), recurrence site (p=0.002) and number of recurrence sites (p=0.001). Primary imaging methods (sonography and chest X-ray) were not inferior to secondary imaging methods (computed tomography, magnetic resonance imaging and positron emission tomography-computed tomography) in the detection of recurrence. The chest X-ray examination only detected three cases (1.14%) of recurrence. Patients assessed with various diagnostic strategies had similar progression-free and overall survival outcomes. CONCLUSIONS: A meticulous evaluation of clinical manifestations might allow recurrence to be discovered in a timely manner in most patients with cervical cancer. Specific diagnostic methods for revealing recurrence were not associated with the survival outcomes.

Minimally invasive versus open radical trachelectomy for early-stage cervical cancer: protocol for a multicenter randomized controlled trial in China.

BACKGROUND: There are limited data comparing the oncologic and fertility outcomes of patients with early-stage cervical cancer (CC) treated by minimally invasive radical trachelectomy (MIRT) or abdominal radical trachelectomy (ART). The purpose of this multicenter study is to compare the oncologic and fertility outcomes of patients treated by MIRT or ART in a randomized controlled manner in China. METHODS: This is a noninferiority, randomized controlled trial performed at 28 Chinese centers; the study is designed to compare the oncologic and fertility outcomes of patients treated by MIRT (robot-assisted or laparoscopic RT) or ART. Patients will be recruited if they have been diagnosed with stage IA1 (with lymphovascular space invasion), IA2, or IB1 CC (with a maximum tumor diameter ≤ 2 cm) in the FIGO 2009 staging system and histological subtypes of squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma and if they are also aged 18 to 40 years. These candidates will be randomly assigned to undergo MIRT or ART. The primary endpoint will be disease-free survival. Secondary endpoints will consist of overall and disease-free survival rates, fertility outcomes, and quality of life. A total of 414 patients are needed to accomplish the study goal, with 90.1% power at a 0.050 significance level to detect an equivalence hazard ratio of 0.75 in the ART group, considering 20% loss to follow-up. DISCUSSION: The results of the trial should provide robust evidence to surgeons regarding options for the surgical approach in patients with early-stage CC who have a strong willingness to preserve fertility. TRIAL REGISTRATION: ClinicalTrials.gov NCT03739944 . Registered on November 14, 2018.

Efficacy of different surgical approaches on survival outcomes in patients with early-stage cervical cancer: protocol for a multicentre longitudinal study in China.

INTRODUCTION: Recent studies have revealed that the oncological survival outcomes of minimally invasive radical hysterectomy (MIRH) are inferior to those of abdominal radical hysterectomy (ARH) in early-stage cervical cancer, but the potential reasons are unclear. METHODS AND ANALYSIS: Each expert from 28 study centres participating in a previously reported randomised controlled trial (NCT03739944) will provide successive eligible records of at least 100 patients who accepted radical hysterectomy for early-stage cervical cancer between 1 January 2009 and 31 December 2015. Inclusion criteria consist of a definite pathological evaluation of stages IA1 (with positive lymphovascular space invasion), IA2 and IB1 according to the International Federation of Gynecology and Obstetrics 2009 staging system and a histological subtype of squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma. The primary endpoint is 5-year disease-free survival between the MIRH and ARH groups. The secondary endpoints include the MIRH learning curves of participating surgeons, 5-year overall survival between the MIRH and ARH groups, survival outcomes according to surgical chronology, surgical outcomes and sites of recurrence and potential risk factors that affect survival outcomes. A subgroup analysis in patients with tumour diameter less than 2 cm will follow the similar flow diagram. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of Peking Union Medical College Hospital (registration no. JS-1711), and is also filed on record by all other 27 centres. The results will be disseminated through community events and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03738969.

Clinical characteristics difference between early and late recurrence of ovarian endometriosis after laparoscopic cystectomy.

BACKGROUND: Ovarian endometriosis is the most frequent type of endometriosis. Despite the use of surgery and medication, many patients suffer from recurrence within near future. Currently, there are no effective clinical characteristics available to predict the time to recurrence in ovarian endometriosis patients. PURPOSE: To identify the effective clinical indicators for early and late endometrioma recurrence, we compared the clinical characteristics of early and late recurrence after treatment. METHODS: We collected 358 patients with ovarian endometriosis who had a minimum of 5 years of postoperative follow-up after undergoing a laparoscopic excision of ovarian endometrioma performed at Peking Union Medical College Hospital from January 2009 to April 2013. RESULTS: A total of 358 patients were recruited in the validation set, with a median follow-up time of 83 months (60-120 months). Till the last follow-up, 68 patients exhibited recurrence. Three-year and 5-year recurrence rates were 9.2% and 15.4%, respectively. Univariate analysis in our study showed that patient with endometrioma surgery history had higher incidence of recurrence in 3 years after re-surgery (OR: 5.594, P = 0.029). Univariate and multivariate analyses using the logistic regression showed that the presence of tenesmus before surgery affected the incidence of early recurrence with a ratio of 57.9% (11/19) and 89.5% (17/19) in 3 years and 5 years after surgery, respectively. CONCLUSIONS: Presence of tenesmus before surgery may be linked to the early recurrence of endometrioma.

Malignant risk of pelvic mass after hysterectomy for adenomyosis or endometriosis.

Pelvic mass onset following a hysterectomy due to benign disease is not rarely seen. Appropriate diagnosis and treatment are of great importance.This study aims to analyze the clinicopathological features of patients who have received surgery for pelvic mass following hysterectomy due to gynecological benign disease, especially endometriosis or adenomyosis.This study retrospectively analyzed the patients undergone reoperation for pelvic mass subsequently to hysterectomy from January 2012 to December 2016 in a tertiary teaching hospital.A total of 247 patients were enrolled in this study. There is a significant difference between the patients with or without a history of endometriosis/adenomyosis. Multivariate analysis showed that the pelvic mass had a higher risk of being ovarian endometrioid carcinoma, ovarian clear cell carcinoma, ovarian endometriosis, and ovarian physiological cysts in patients with a history of adenomyosis/endometriosis.The pathology of the subsequent pelvic mass inclines to be benign, includes ovarian endometriosis, ovarian physiological cysts, and pelvic encapsulated effusion. Postoperative adjuvant therapy for those received hysterectomy due to endometriosis/adenomyosis, like gonadotropin releasing hormone agonists (GnRHa), may contribute to the prevention of benign pelvic mass. Patients with a history of hysterectomy due to endometrisos/adenomyosis tend to have a shorter time interval between hysterectomy and pelvic malignant tumors onset.

The clinicopathological characteristics and survival outcomes of endometrial carcinoma coexisting with or arising in adenomyosis: A pilot study.

Little is known about the epidemiological and clinicopathological characteristics of endometrial endometrioid carcinoma (EEC) coexisting with or arising in adenomyosis (EEC-A or EEC-AIA) due to their rarity. This study compared EEC-A and EEC-AIA with endometrial carcinoma without adenomyosis. Cases of endometrial cancer treated at the study center from June 1, 2010, to June 1, 2017, were reviewed. The epidemiological, clinicopathological characteristics and survival outcomes were compared among three groups of endometrioid subtypes: group A, stage IA endometrial carcinoma patients without coexisting adenomyosis; group B, patients with EEC-A; and group C, patients with EEC-AIA. Among the 2080 patients reviewed, groups A, B, and C included 1043, 230 and 28 patients, respectively. Patients in group A and group B had similar clinicopathological and survival outcomes. Patients in group C were significantly younger and had less gravidity and parity than patients in groups A and B. More tumors from group C were grade 1, and they had a smaller maximum diameter and less mismatch repair deficiency than those from groups A and B. After a median follow-up of 57.0 months, the 5-year disease-free survival (DFS) rates of groups A, B and C were 96%, 91% and 100% (p = 0.045), respectively; the 5-year overall survival (OS) rates were 98%, 93% and 100%, respectively (p = 0.001), in the Kaplan-Meier analysis. However, these difference disappeared in a subgroup of stage IA patients in univariate and multivariate analysis. Cox regression analysis in stage IA patients also revealed no significant differences in survival outcome across the three groups. In conclusion, EEC-AIA exhibited specific clinicopathological characteristics that were probably associated with favorable survival outcomes. The characteristics and survival outcomes of EEC-A were similar to those of EEC without adenomyosis in stage IA patients.

Research of the potential biomarkers in vaginal microbiome for persistent high-risk human papillomavirus infection.

BACKGROUND: Vaginal dysbiosis may paly role in increased risk of human papillomavirus (HPV) infection. This study aims to explore potential vaginal microbiome biomarkers, to predict persistent high-risk HPV (HR-HPV) infection and cervical intraepithelial neoplasia (CIN) 2+, and to find novel treatment targets for HPV infection. METHODS: A total of 329 women aged 20-69 were enrolled in this study, including 59 with cervical persistent HPV infection irrespective of cytology status (group A), 139 with incident HPV infection (group B), and 131 without HPV infection (group C). Vaginal microbiome composition was determined by sequencing of barcoded 16S rDNA gene fragments (V4) on Illumina HiSeq2500. RESULTS: In genus level, the relative abundance of Prevotella, Porphyromonas and Enterococcus were significantly the highest in group A, while Bacteroides was the lowest in group A. In species level, we found the relative abundance of Prevotella bivia, Enterococcus durans and Porphyromonas uenonis were the highest in group A while Lactobacillus iners was significantly under-represented in group A than the other two, and Prevotella disiens was over-represented in group C than the other two groups. CONCLUSIONS: A predominance of Prevotella bivia, Enterococcus durans and Porphyromonas uenonis with a concomitant paucity of Lactobacillus iners and Prevotella disiens may relate to HPV persistent infection. Furthermore, the relative abundance of Prevotella bivia being over 0.05554% with Prevotella disiens being under 0.02196% may be a good predictor for appearance CIN2+ for those diagnosed with the other 12 types of HR-HPV persistent infection but normal ThinPrep cytology test (TCT) testing. The exact molecular mechanism of the vaginal microbiome in the course of persistent HR-HPV infection and cervical neoplasia should be further explored. Future research should include intervention of vaginal microbiome composition to reverse the course of HR-HPV infection and the natural history of cervical neoplasia.

Clinical analysis of high risk factors for pelvic malignant tumors after hysterectomy for benign diseases.

To analyze the clinicopathological characteristics of pelvic masses after hysterectomy for benign diseases, and to analyze the related factors of benign and malignant pelvic masses.This study retrospectively analyzed the patients undergone reoperation for pelvic mass subsequently to hysterectomy for benign disease from January 2012 to December 2016 in Peking Union Medical College Hospital.A total of 247 patients were enrolled in this study, of which 34.01% were diagnosed with malignant tumors, and 65.99% benign tumors. Comparing the clinicopathological data of patients with benign and malignant pelvic masses, significant differences were found between the 2 groups with regard to their ages of having hysterectomy and pelvic mass resection, and the time intervals between the onset of pelvic mass and hysterectomy. In addition, patients with malignant masses tended to complain of abdominal distension and abdominal pain, while most of those with benign masses were diagnosed during physical examination. Patients with malignant pelvic masses had medical imagines of mixed masses, extraovarian derivation, as well as elevated carbohydrate antigen-125 (CA 125). Multivariate analysis showed that ages of having hysterectomy, physical examination results, abnormal defecation, cystic and solid masses, and elevated CA 125 level were independent risk factors for benign and malignant pelvic masses.For patients having pelvic masses following hysterectomy for benign diseases, if they had hysterectomy later in their lives, and their masses were not found during physical examination, and had abnormal defecation, mixed cystic solid mass as well as elevated serum CA 125, it is suggested that special attention should be paid to the possibility of malignant tumors.

Risk factors for postoperative recurrence of ovarian endometriosis: long-term follow-up of 358 women.

OBJECTIVE: To explore the risk factors for the recurrence of endometrioma and the risk factors for the recurrence of endometriosis-related pain after long-term follow-up. METHODS: This study retrospectively analyzed 358 women with endometriomas who had a minimum of 5-years follow up after laparoscopic endometrioma excision, which was performed at Peking Union Medical College Hospital from January 2009 to April 2013. All women were divided into recurrence group and nonrecurrence group. Analysis was performed with regard to preoperative history, laboratory analysis, findings during surgery, and symptoms during follow-up, including improvement and recurrence. RESULTS: The cumulative incidence rates of recurrence from 5 to 10 years after surgery were 15.4, 16.8, 19.3, 22.5, 22.5, and 22.5%, respectively. Significant differences were found between two groups in terms of age at surgery (RR: 0.764, 95% CI: 0.615-0.949, p = 0.015), duration of dysmenorrhea (RR: 1.120, 95% CI: 1.054-1.190, p < 0.001), presence of adenomyosis (RR: 1.629, 95% CI: 1.008-2.630, p = 0.046), CA125 level (RR: 1.856, 95% CI: 1.072-3.214, p = 0.021) and severity of dysmenorrhea. The severity of dysmenorrhea (RR: 1.711, 95% CI: 1.175-2.493, p = 0.005) and postoperative pregnancy (RR: 0.649, 95% CI: 0.460-0.914, p = 0.013) were significantly correlated with endometrioma recurrence in the multivariate analysis. No significant associations were found between the recurrence rate and gravida, parity, body mass index, infertility, leiomyoma presence, the size of ovarian endometrioma, the presence of deep infiltrating endometriosis, disease stage or postoperative medication. CONCLUSIONS: The severity of dysmenorrhea and postoperative pregnancy were independent risk factors for the recurrence of ovarian endometriomas after surgery during the long-time follow up.

Efficacy of different surgical approaches in the clinical and survival outcomes of patients with early-stage cervical cancer: protocol of a phase III multicentre randomised controlled trial in China.

INTRODUCTION: In the last three decades, minimally invasive surgery (MIS) for radical hysterectomy (RH) has become a popular treatment option for early-stage cervical cancer. However, a recently published randomised controlled trial (LACC trial) and an epidemiological study in the USA revealed strong evidence against the survival advantage of MIS for RH. However, the influencing factors of research centres and the learning curves of surgeons in these studies lacked sufficient evaluation. The efficacy of different surgical approaches for early-stage cervical cancer in the clinical and survival outcomes remains to be validated. METHODS AND ANALYSIS: Patients diagnosed with FIGO (2009) stage IA1 (with lymphovascular space invasion), IA2 or IB1 cervical cancer with histological subtype of squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma will be recruited in this multicentre randomised controlled study. Patients will be randomly assigned to undergo MIS (robot-assisted or laparoscopic RH) or abdominal RH. Within 2 years, 1448 patients in 28 centres in China will be recruited to meet the criteria of a non-inferiority threshold of HR of 1.6 with bilateral nominal α <0.05 and power of 0.8. All surgeries will be performed by the indicated experienced surgeons. At least 100 RH cases in the individual past one decade of practice will be analysed as proof of learning curves. The primary objective of this study is 5-year disease-free survival. The secondary objectives include the overall survival rate, progression-free survival rate, disease-free survival rate, cost-effectiveness and quality of life. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of Peking Union Medical College Hospital and is filed on record by all other centres. Written informed consent will be obtained from all eligible participants before enrolment. The results will be disseminated through community events, academic conferences, student theses and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03739944.

Comparison of screening strategies for Lynch syndrome in patients with newly diagnosed endometrial cancer: a prospective cohort study in China.

BACKGROUND: The prevalence of Lynch syndrome and screening strategies for this disorder in Chinese patients with endometrial cancer have seldom been investigated. Such data would be essential for the screening, prevention, genetic counseling, and treatment of Lynch syndrome. The purpose of this prospective study was to determine the accuracy of the mismatch repair (MMR) protein immunohistochemistry (IHC), microsatellite instability (MSI) test, and clinical diagnostic criteria in screening for Lynch syndrome-associated endometrial cancer (LS-EC) in a prospective Chinese cohort. METHODS: All patients with newly diagnosed endometrial cancer (EC) were evaluated using clinical diagnostic criteria (Amsterdam II criteria and the revised Bethesda guidelines), MSI test, and IHC of MMR proteins in tumor tissues. For all patients, the screening results were compared with results of germline sequencing for pathogenic variants of MMR genes. RESULTS: Between December 2017 and August 2018, a total of 111 unselected patients with newly diagnosed EC were enrolled. Six patients (5.4%) harbored a pathogenic germline mutation of MMR genes: 1 had a mutation in MutL homolog 1 (MLH1), 2 in MutS homolog 2 (MSH2), and 3 in MutS homolog 6 (MSH6). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying LS-EC were 33.3%, 88.6%, 14.3%, and 95.9%, for the clinical criteria, 66.7%, 75.0%, 14.3%, and 97.3% for IHC of MMR proteins, 100%, 89.9%, 33.3%, and 100% for MSI test, and 100%, 72.4%, 20.0% and 100% for combined IHC and MSI test, respectively. The combination of IHC and MSI test had higher sensitivity and PPV than the clinical criteria (p = 0.030). MSI test and IHC were highly concordant for LS-EC screening (73/77, 94.8%). CONCLUSION: The accuracy of the combination of IHC of MMR proteins and MSI test for screening LS among Chinese patients with EC was superior to that of the clinical criteria. Trial registration NCT03291106. Registered on September 25, 2017.