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Background: The aim of the study is to evaluate the risk factors of anastomotic leakage (AL) and develop a nomogram to predict the risk of AL in surgical management of primary ovarian cancer. Methods: We retrospectively reviewed 770 patients with primary ovarian cancer who underwent surgical resection of the rectosigmoid colon as part of cytoreductive surgery between January 2000 to December 2020. AL was defined based on radiologic studies or sigmoidoscopy with relevant clinical findings. Logistic regression analyses were performed to identify the risk factor of AL, and a nomogram was developed based on the multivariable analysis. The bootstrapped-concordance index was used for internal validation of the nomogram, and calibration plots were constructed. Results: The incidence of AL after resection of the rectosigmoid colon was 4.2% (32/770). Diabetes (OR 3.79; 95% CI, 1.31–12.69; p = 0.031), co-operation with distal pancreatectomy (OR, 4.8150; 95% CI, 1.35–17.10; p = 0.015), macroscopic residual tumor (OR, 7.43; 95% CI, 3.24–17.07; p = 0<001) and anastomotic level from the anal verge shorter than 10 cm (OR, 6.28; 95% CI, 2.29–21.43; p = 0.001) were significant prognostic factors for AL on multivariable analysis. Using four variables, the nomogram has been developed to predict anastomotic leakage: https://ALnomogram.github.io/. Conclusion: Four risk factors for AL after resection of the rectosigmoid colon are identified from the largest ovarian cancer study cohort. The nomogram from this information provides a numerical risk probability of AL, which could be used in preoperative counseling with patients and intraoperative decision for accompanying surgical procedures and prophylactic use of ileostomy or colostomy to minimize the risk of postoperative leakage. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

We conducted a prospective phase II study on whether extended‐field irradiation (EFI) confers survival benefits depending on hypoxic markers in locally advanced uterine cervical cancer (LAUCC). RNA‐seq was performed to identify immune and hypoxic gene signatures. A total of 288 patients were randomized to either EFI or pelvic radiotherapy (PRT). All patients completed chemoradiotherapy. Overall, significantly higher 5‐year para‐aortic recurrence free survival (PARFS) rate occurred in EFI (97.6%) than in PRT group (87.2%), with marginal tendency to improve disease‐free survival (DFS; 78% vs 70%, P =.066). Subgroup analyses were performed based on carbonic anhydrase 9 (CA9)‐only positive, CA9/hypoxia‐inducible factor (HIF) double positive and CA9 negative. In the CA9‐only positive, EFI successfully increased 5‐year PARFS (100% vs 76.4%, P =.010), resulting in significantly improved long‐term DFS (85.7% vs 54.7%, P =.023) compared to the PRT, while there was no such benefit of EFI in the CA9/HIFs double positive. RNA‐seq analysis identified distinct immunehigh subgroup with negative correlation with hypoxia gene signatures (R = −.37, P <.01), which showed a higher 5‐year DFS than the immunelow (P =.032). Hypoxia‐related genes were upregulated in the CA9/HIFs double positive compared to CA9 negative (P <.05). Only 17.4% of patients in CA9‐negative group showed immunelow signatures, while 40.0% of patients in the double‐positive group exhibited immunelow signatures. In conclusion, EFI improved PARFS significantly in all patients, but therapeutic efficacy of EFI in terms of improved DFS was solely observed in CA9‐only positive LAUCC, and not in CA9/HIFs double‐positive subgroup. RNA‐seq analysis suggested that hypoxia‐induced immunosuppression may be related to treatment resistance in LAUCC. [ABSTRACT FROM AUTHOR]

Background: Ureteral reconstruction is required after surgical resection of the tumor invading the urinary tract in ovarian cancer with low incidence. There are no currently reported surgical outcomes of ureteral reconstruction during cytoreductive surgery. The aim of the study is to investigate the clinical features and surgical outcomes of ureteral reconstruction during primary, interval and secondary cytoreductive surgery for ovarian cancer.  METHODS: A total of 3226 patients who underwent primary, interval or secondary cytoreductive surgery for ovarian cancer between January 2000 and May 2021 were reviewed. Fifty-six patients who underwent ureteral reconstruction during cytoreductive surgery were included in the analysis.  RESULTS: Ureteral reconstruction was required in 1.7% (56/3226) of ovarian cancer patients. Of the 56 patients who underwent ureteral reconstruction during cytoreductive surgery, 35 (62.5%) had primary ovarian cancer, and 21 (37.5%) had recurrent ovarian cancer. The median tumor size invading the lower urinary tract was 2.0 cm (range, 0.4-9.5 cm). Ureteroneocystostomy with direct implantation (51.8%) and psoas hitch (8.9%), transureteroureterostomy (7.1%), and ureteroureterostomy (32.1%) were required as part of cytoreductive surgery. Complete cytoreduction with ureteral reconstruction was achieved in 83.9% (47/56) and the rest of the patient population (16.1%) achieved a gross residual tumor size of less than 1 cm. All complications, including hydronephrosis (33.9%), were managed, none resulting in long-term sequelae. In primary ovarian cancer, the 5-year disease-free survival and overall survival were 50.0% and 89.5%, respectively. In patients with recurrent ovarian cancer, the 5-year disease-free survival and overall survival were 23.6% and 64.0%, respectively.Conclusions: Ureteral reconstruction as a part of cytoreductive surgery for ovarian cancer could be performed with acceptable morbidities. Complete cytoreduction by a multidisciplinary surgical team, including urologic oncologists, should be pursued for the surgical management of ovarian cancer.Trial Registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Objective: This study investigated site-specific differences in clinical factors for recurrence in patients who were newly diagnosed and treated for endometrial cancer. A model for predicting recurrence sites was generated.Methods: Electronic medical records' data were retrieved from January 2006 to December 2018 for patients who were diagnosed with endometrial cancer at the National cancer center in Korea. Recurrence sites were classified as local, regional, or distant. We used multinomial logistic regression models that modeled the log-odds for the three recurrence sites relative to non-recurrence as a linear combination of possible risk factors for the recurrence of endometrial cancer.Results: The data of 611 patients were selected for analysis; there were 20, 12, and 25 cases of local, regional, and distant recurrence, respectively, and 554 patients had no recurrence. High-grade disease was associated with local recurrence; non-endometrioid histology and parametrial invasion were risk factors for regional recurrence; additionally, parametrial invasion and no lymphadenectomy were associated with distant metastasis.Conclusion: We identified different risk factors specific for each type of recurrence site. Using these risk factors, we suggest that individually tailored adjuvant treatments be introduced for patients. [ABSTRACT FROM AUTHOR]

Backgrounds: We aimed to evaluate the prognosis in patients with synchronous endometrial and ovarian cancer (SEOC) by comparing the differences between double primary cancer (DPC) and metastatic cancer (MC).Methods: The medical records of 47 patients diagnosed synchronously with endometrial and ovarian cancer between January 2006 and December 2018 were retrospectively reviewed. Twenty-eight and 19 patients were diagnosed with DPC and MC, respectively. Demographics, recurrence-free survival (RFS), and 5-year overall survival (OS) were compared. The clinical factors affecting survival were evaluated using univariate and multivariate analyses.Results: The demographics were not different between both groups. Endometrioid histology and the International Federation of Gynecology and Obstetrics grade were higher in the MC group than in the DPC group (42.1% vs. 10.7%; P = 0.018, P = 0.002, respectively). The ratio of post-operative adjuvant therapy was not different in both groups. Recurrence occurred in five patients with DPC and seven with MC. The difference in RFS was not significantly different (P = 0.131) but the OS was different between both groups (P = 0.020). Histology and para-aortic lymph node metastasis were associated wtih RFS in univariate analysis, but no difference was found in multivariate analysis.Conclusions: Although DPC patients had longer OS, multivariate analysis did not identify any influential factors. Focus should be placed on defining the appropriate adjuvant treatment for high-risk patients, which will improve prognosis, rather than on discriminating between DPC and MC. [ABSTRACT FROM AUTHOR]

The cervical microbiome is associated with cervical cancer risk, but how microbial diversity and functional profiles change in cervical cancer remains unclear. Herein, we investigated microbial-compositional and functional differences between a control group and a high-grade cervical intraepithelial neoplasia and cervical cancer (CIN2/3-CC) group. After retrospective collection of 92 cervical swab samples, we carried out 16S rRNA amplicon sequencing on 50 and 42 samples from the control and CIN2/3-CC groups, respectively. The EzBioCloud pipeline was applied to identify the genomic features associated with the groups using 16S rRNA data. A linear discriminant analysis effect size (LEfSe) was performed to assess the enrichment in the assigned taxonomic and functional profiles. We found a lower richness in the control group relative to the CIN2/3-CC group; however, the β-diversity tended to be similar between the groups. The LEfSe analysis showed that a phylum Sacchaaribacteria_TM7, 11 genera, and 21 species were more abundant in the CIN2/3-CC group and that one uncharacterized Gardnerella species was more abundant only in the control group. Further characterization of the functional pathways using EzBioCloud showed that the 4 KEGG orthologs (Phosphotransferase system [PTS] sucrose-specific IIA, IIB, IIC components and PTS cellubiose-specific IIC component) were involved in the KEGG pathway of starch and sucrose metabolism. The two pathways of folate biosynthesis and oxidative phosphorylation were more abundant in the CIN2/3-CC group. Further confirmation of these results in larger samples can help to elucidate the potential association between the cervical microbiome and cervical cancer. [ABSTRACT FROM AUTHOR]

Tobacco smoking is established as a cofactor of human papillomavirus (HPV) for cervical cancer risk. However, the role of secondhand smoking in cervical carcinogenesis is controversial. We aimed to assess the association between secondhand smoking and high risk- (HR-) HPV persistence, a pivotal event in development of cervical cancer. In total, 9,846 women who underwent health-screening examinations from 2002 to 2011 at the National Cancer Center, Korea, were included. Secondhand smoking was defined as being exposed to secondhand smoke at home or in the workplace. Multivariate logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (CIs) for risks of HR-HPV infection at baseline (N, 9,846, negative vs. positive), 1-year persistence (n, 1,237, 1-year negative vs. 1-year persistence), and 2-year persistence (n, 481, 2-year negative vs. 2-year persistence). Active smoking, secondhand smoking, and secondhand smoking in nonactive smokers had no association with these risks. Among alcohol drinkers, secondhand smoking in nonactive smokers had higher risks of HR-HPV infection at baseline (OR = 1.25, 95% CI = 1.05–1.48, p for multiplicative interaction = 0.003), 1-year persistence (1.75, 1.14–2.68, 0.004), and 2-year persistence (2.96, 1.42–6.15, 0.006), when compared to HR-HPV negative, 1-year negative, and 2-year negative categories, respectively. However, among nonalcohol drinkers, there was no association between smoking or secondhand smoking status and these risks. These findings suggest that women exposed to secondhand smoking at home or in the workplace might be at high risk of HR-HPV persistence when it is combined with alcohol drinking, even though neither active smoking nor secondhand smoking independently affects the risk. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the incidence of colon cancer as a second primary cancer (CCSPC) and the survival outcomes of women with and without CCSPC after the diagnosis of endometrial cancer (EC).Methods: The standardized incidence ratio (SIR) of CCSPC and survival outcomes of EC survivors with and without CCSPC were analyzed using data from January 1 1993 to December 31 2011, obtained from the Korea Central Cancer Registry.Results: Of 14,797 EC survivors, 147 (0.99%) developed CCSPC after an average interval of 5.5 years. The SIR of CCSPC among EC survivors was 2.56, higher than that of colon cancer in the general population. The SIR of CCSPC was highest for the ascending (3.77), followed by the transverse (3.45), descending colon (2.06), and rectum (1.99). The risk of a proximal site of CCSPC was high, especially within 5 years after the diagnosis of EC in the ascending (SIR, 4.37) and transverse (4.91) colon, and in young survivors (< 60 years) in the ascending (5.19) and transverse (3.82) colon. The 5- and 10-year overall survival rates were 84.8 and 80.4% among survivors with EC only and 89.2 and 76.3% for survivors with CCSPC, respectively.Conclusions: The risk of CCSPC among EC survivors increases especially in the proximal colon in young survivors. These results could be used for surveillance and counseling of EC survivors. [ABSTRACT FROM AUTHOR]

Objective. The purpose of this study was to (i) determine the cervical microbial composition in different abortion samples and to (ii) investigate the correlation between spontaneous abortion and cervical microbes in Korean women. Methods. We collected cervical swabs from women who had never undergone abortion (N=36), had spontaneous abortion (N=23), and had undergone induced abortion (N=88) and subjected those samples to 16S rRNA pyrosequencing. Further, factor analysis and correlation between cervical microbiota and spontaneous abortion were evaluated by logistic regression analysis. Results. In spontaneous abortion women, 16 S rRNA gene sequences showed significant increases in Atopobium vaginae, Megasphaera spp., Gardnerella vaginalis, Leptotrichia amnionii, and Sneathia sanguinegens compared to women in nonabortion group. In multivariate logistic regression analysis, A. vaginae (OD = 11.27; 95% = 1.57–81), L. amnionii (OD = 11.47; 95% = 1.22–107.94), S. sanguinegens (OD = 6.89; 95% = 1.07–44.33), and factor 1 microbes (OD = 16.4; 95% = 1.88–42.5) were strongly associated with spontaneous abortion. Conclusions. This study showed a high prevalence of L. amnionii, A. vaginae, S. sanguinegens, and factor 1 microbes in spontaneous abortion and association with spontaneous abortion in Korean women. [ABSTRACT FROM AUTHOR]

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We explored the prevalence of smoking, alcohol consumption, physical activity, and obesity in cervical cancer survivors and examined associations between sociodemographic factors and each health behavior. We studied 448 cervical cancer survivors ≥2 years after their initial diagnosis who had completed treatment. The total sample consisted of these survivors, and 4,480 cancer-free controls who were grouped into 5-year age cohorts and matched to the survivors in terms of both education and monthly household income. The prevalence of current smoking, current alcohol consumption, physical inactivity, and obesity in cervical cancer survivors (2.68, 23.88, 62.02, and 32.81%, respectively) did not differ significantly from those of matched non-cancer controls. Age (younger), marital status (married), and education (≥college) were associated with lower probabilities of current alcohol consumption (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.88–0.95; OR = 0.42, 95% CI = 0.23–0.78; OR = 0.49, 95% CI = 0.25–0.97, respectively). A monthly household income ≥$2,000, being employed, and self–rated health status (less healthy) were associated with physical inactivity (OR = 0.61, 95% CI = 0.37–0.99; OR = 2.16, 95% CI = 1.36–3.42; OR = 1.94, 95% CI = 1.23–3.05, respectively). Both age and number of years since diagnosis were associated with obesity (OR = 1.04, 95% CI = 1.01–1.08; OR = 0.38; 95% CI = 0.20–0.72, respectively). The health behaviors of cervical cancer survivors did not differ from those of matched cancer-free controls. As health behaviors are modifiable, identification of cervical cancer survivors who are at risk of an unhealthy lifestyle would allow individual- and population-based intervention programs to more effectively use their limited resources. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine whether the preoperative diameter of cardiophrenic lymph nodes (CPLNs) along the short and long axes, determined via computed tomography (CT), predicts CPLN metastasis in patients with advanced epithelial ovarian cancer. Methods: A total of 31 patients with primary advanced ovarian cancer who had CPLN dissection underwent preoperative CT that was reviewed twice by a radiologist blinded to the final pathology. An array of CT features and clinical factors [age, cancer antigen 125 (CA 125)] were compared between metastasis-positive and metastasis-negative CPLNs using the t test and Fisher's exact test. The optimal CPLN dimensions that best predicted metastasis were calculated using a receiver operating characteristic (ROC) curve, and were applied to find the correlation with other CT findings. Results were validated in an independent test set of nine patients by using the best cutoff value to predict metastasis. Results: Pathological evaluation revealed metastasis-positive CPLNs in 19 patients and metastasis-negative CPLNs in 12 patients. Metastasis-positive CPLNs had significantly reduced short axes than those of negative CPLNs (5.6 ± 1.7 and 7.8 ± 2.2, respectively; p < 0.001). ROC curve analysis showed that a cutoff value of 7 mm for the short axis demonstrated the largest area under the curve (0.789; p < 0.0007), with 63.16 % sensitivity and 83.33 % specificity. The presence of peritoneal metastasis and abdominopelvic adenopathy strongly related with CPLN adenopathy. Accuracies were 66.7 % (six of nine patients) based on the cutoff value in the independent test set. Conclusions: The probability of detecting CPLN metastasis in patients with advanced ovarian cancer was approximately 85 % when the short axis of the CPLN was >7 mm in preoperative CT scans. Patients with CPLNs of this size may be candidates for CPLN dissection in order to confirm the pathological diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this study was to investigate clinical manifestations of lower extremity edema (LEE) after lymph node dissection in patients with primary endometrial cancer. Methods: Women with primary endometrial cancer who underwent staging surgery between November 2001 and March 2011 were included in the study. Medical records and/or responses to the Gynecologic Cancer Lymphedema Questionnaire (GCLQ) were used for LEE evaluation. Results: All 154 patients underwent pelvic lymph node dissection, and 126 patients (81.8 %) underwent paraaortic LN dissection. The median age of the patients was 52 years, the majority had stage I cancer (78.6 %), and most had endometrioid histology (90.9 %). The most frequent GCLQ responses were 'experienced swelling' (35.7 %), 'experienced numbness' (30.5 %), 'experienced heaviness' (29.9 %), and 'experienced aching' (29.9 %). Sixty-four patients (41.6 %) had previous (9/64, 14.1 %) and/or current (55/64, 85.9 %) patient-reported LEE. Most patients developed LEE within 12 months after surgery (39/56, 69.6 %), and LEE lasted for more than 12 months in most patients (45/56, 80.4 %). Three patients reported recurrent LEE after recovery. Multivariate logistic regression identified the number of dissected pelvic lymph node (≥21) as a risk factor for LEE [odds ratio (OR) 3.28; 95 % confidence interval (CI) 1.058-10.136] and postoperative radiotherapy (OR 3.81, 95 % CI 1.67-8.69). Conclusions: LEE developed in more than one-third of patients with endometrial cancer after surgery, and LEE lasted for more than 12 months in most patients. A high number of dissected pelvic lymph nodes and postoperative radiotherapy is associated with LEE. [ABSTRACT FROM AUTHOR]

Background: This study investigated the clinical manifestations of lower extremity edema (LEE) in locally advanced cervical cancer patients treated with two different strategies. Methods: In total, 79 cervical cancer survivors with International Federation of Gynecology and Obstetrics stage IB2-IIB were included. Six survivors with stage IB1 and who had been suspicious for lymph node metastasis on pretreatment image also were included. Forty-two patients received radiotherapy after pretreatment laparoscopic surgical staging (Group 1), and 43 patients received primary radiotherapy (Group 2). The patients' medical records and survey results of the Korean version of the Gynecologic Cancer Lymphedema Questionnaire (GCLQ-K) were analyzed. Results: The incidence of LEE was higher in Group 1 than in Group 2 (69.0 vs. 11.6 %; P < 0.001). The duration of LEE was longer in Group 1 (mean 77.3 vs. 9.4 months). At the time of survey, 47.6 % of the patients in Group 1 were clinically diagnosed with lymphedema compared with no patients in Group 2. In GCLQ-K, the mean symptom cluster scores for general swelling (0.74 vs. 0.09; P < 0.001), limb swelling (0.22 vs. 0.00; P = 0.006), and heaviness (0.45 vs. 0.23; P = 0.033) were significantly higher in Group 1. One patient in Group 1 developed lymphedema-related angiosarcoma that was diagnosed at 7.8 years after surgery. Conclusions: Patients with cervical cancer who underwent radiotherapy after laparoscopic surgical staging more commonly experienced LEE and related symptoms than patients who underwent primary radiotherapy. As LEE decreases patients' quality of life, it should be considered during patient consultation and surveillance. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to identify the uptake rate of risk-reducing salpingo-oophorectomy (RRSO) and the factors affecting this rate among female BRCA1 or BRCA2 mutation carriers at the National Cancer Center of Korea. Methods: Between April 2007 and December 2014, 450 women underwent BRCA gene testing, and 97 women were found to have BRCA1/2 mutations. Through the review of medical records, 42 candidates for RRSO were identified. Of these, 22 underwent RRSO. Demographic, clinical, and consultation-related factors were compared between the RRSO and non-RRSO groups. Results: The uptake rate of RRSO was 52.4 %. The mean time interval between genetic testing and surgery in the RRSO group was 7.3 months (range 0.6-33.9). The prevalence of amenorrhea was greater in the RRSO group than in the non-RRSO group (59.1 % vs. 20.0 %; P = 0.010). More women in the RRSO group were consulted with gynecologic oncologists (95.5 % vs. 60.0 %; P = 0.008). In multivariate analyses, amenorrhea at the time of genetic counseling (OR 16.44; 95 % CI 1.16-232.82; P = 0.038) and consultation with gynecologic oncologists (OR 30.78; 95 % CI 1.34-707.21; P = 0.032) were identified as factors affecting the carrier's decision to undergo RRSO. One patient in the non-RRSO group (5.0 %) developed primary peritoneal carcinoma, which was diagnosed 4.6 years after genetic testing. Conclusions: The uptake rate of RRSO among BRCA1/2 mutation carriers was affected by the presence of amenorrhea and consultation with gynecologic oncologists. Gynecologic oncologists with clinical experience with ovarian cancer should play a major role in aiding carriers' decision-making concerning RRSO. [ABSTRACT FROM AUTHOR]

Purpose: This prospective study aimed to examine the combined effect of viral load and alcohol consumption on the risk of persistent high-risk (HR) human papillomavirus (HPV) infection. Methods: Among women undergoing health screening between 2002 and 2011 at the National Cancer Center, 284 and 122 women with HR-HPV infection and cytological findings of low-grade squamous intraepithelial or lower-grade lesions were followed up for 1 and 2 years, respectively. Multivariate logistic regression analysis was performed, and the relative excess risk due to interaction (RERI) and synergy index (S) were calculated. Results: Among drinkers, the risks of 1-year (odds ratio [OR] 4.09, 95% confidence interval [CI] 2.05–8.18) and 2-year persistence (OR 8.08, CI 2.36–27.6) were significantly higher for high HPV loads than for low HPV loads; this association was not seen for non-drinkers. The risks for 1-year (OR 4.14, CI 1.89–9.05) and 2-year persistence (OR 6.61, CI 2.09–20.9) were significantly higher in subjects with a high HPV load who were also drinkers than in those who were non-drinkers. A high HPV load together with a longer drinking duration or higher alcohol consumption was associated with increased risks of 1-year (OR 3.07, CI 1.40–6.75 or OR 2.05, CI 0.87–4.83) and 2-year persistence (OR 6.40, CI 1.72–23.8 or OR 4.14, CI 1.18–14.6). The synergistic effect of alcohol consumption and HR-HPV load was stronger on the risk of 2-year persistence (RERI = 3.26, S = 2.38) than on the risk of 1-year persistence (RERI = 1.21, S = 1.63). Conclusions: The synergistic effect of HR-HPV load and alcohol consumption was associated with the risk of HR-HPV persistence and was stronger for longer-term HR-HPV infection. Limiting alcohol consumption might be an important measure to prevent the development of cervical cancer in women with a high HR-HPV load. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to describe the features of patients with brain metastasis from cervical cancer. Material and Methods: The medical records of patients with cervical cancer between February 2001 and June 2011 were reviewed retrospectively. Clinical characteristics, symptoms, treatment and survival in patients with brain metastasis were analyzed. Results: Eleven patients with brain metastasis from cervical cancer were identified, representing an incidence of brain metastasis in the study population of 0.45%. Median patient age at initial diagnosis of cervical cancer was 50 years (range 33-75 years). Non-squamous cell carcinoma was diagnosed in six (54.5%) of the 11 patients, with small cell carcinoma diagnosed in two patients. Ten of the 11 patients had lung-related metastasis at presentation; eight patients had lung metastasis, one had mediastinal lymph node metastasis, and one had pleural metastasis. The median interval from diagnosis of cervical cancer to identification of brain metastasis was 15.4 months (range 3.4-83.3 months). Nine patients presented with neurologic symptoms, such as headache, nausea, vomiting, seizure and extremity weakness. Initially, six patients received whole brain radiotherapy: three patients received chemotherapy; one underwent surgery; and one patient refused treatment. The median survival time after diagnosis of the brain metastases was 5.9 months (range 0.7-19 months). Conclusion: The prognosis after diagnosis of the brain metastasis in patients with uterine cervical cancer is poor. The small cell type and lung metastasis seem to be related with brain metastasis and may be regarded as risk factors. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and toxicity of combined paclitaxel and carboplatin treatment for persistent or recurrent uterine sarcoma. Methods: Paclitaxel was administrated at 175 mg/m intravenously over 3 h plus carboplatin at AUC 5 intravenously over 30 min every 3-week cycle in patients with recurrent or progressive uterine sarcoma, who were unsuitable candidates for curative treatment with either surgery or radiotherapy. The Simon's two-stage optimal design was chosen for defining the total number of patients required for the phase II study. A total of 13 patients were entered in the study at the first stage of trial. A median of four cycles were administrated per patient, with a range of one to nine cycles. Prior to the study, 4 (30.8 %) of the 13 patients had received radiotherapy or chemotherapy. The response was measured by evaluation of the size of the mass by CT scan. Results: The overall response rate was 15.4 % (2/13), with two patients exhibiting partial responses. There was 1 (7.7 %) case of stable disease and 9 (69.2 %) cases of progression disease. The median progression free survival was 2.23 months (95 % confidence interval 1.94-3.67). Peripheral neuropathy and hematologic toxicity, including anemia and neutropenia, were the most frequent adverse events. One patient died from treatment-related toxicities. Conclusions: Paclitaxel in combination with carboplatin demonstrated acceptable levels of toxicity, but it was not active in the treatment of recurrent or progressive uterine sarcoma. This regimen might have limited role for advanced uterine sarcomas. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: The purpose of this study was to evaluate the intra- and postoperative urologic complications and management in patients with cervical or endometrial cancer treated with laparoscopic radical hysterectomy and lymphadenectomy. Methods: We retrospectively reviewed the medical records of 146 patients with cervical or endometrial cancer who underwent total laparoscopic radical hysterectomy with lymphadenectomy between August 2002 and April 2011. The intra- and postoperative urologic complications were analyzed. Results: Double ureteral stents were inserted prophylactically in 13 patients (8.9 %), 2 of whom had postoperative urologic complications. Nine patients (6.2 %) had postoperative urologic complications. Of four patients with ureterovaginal fistulas, two were treated conservatively with cystoscopic placement of ureteral stents and two underwent ureteroneocystostomies. Vesicovaginal fistulas occurred in two patients, both of whom underwent vesicovaginal fistula repairs. One patient noted to have a bladder injury intraoperatively had a laparoscopic repair, and one patient noted to have a ureteral injury postoperatively was treated conservatively with cystoscopic placement of ureteral stents. Conclusions: Iatrogenic lower urinary tract injuries during laparoscopic radical hysterectomy are relatively common complications. Intraoperative prophylactic ureteral stent insertion and the early detection of urologic complications postoperatively is advised for patients who undergo laparoscopic radical hysterectomies. [ABSTRACT FROM AUTHOR]

Objective: The prognosis of stage IVB cervical cancer is generally poor. In the current study, treatment outcomes were evaluated in patients with International Federation of Gynecologic Oncology stage IVB cervical cancer treated with radiotherapy and chemotherapy for progression-free survival (PFS) and treated-related toxicities. Study Design: The medical records of the patients with stage IVB cervical cancer who were treated at the National Cancer Center, South Korea were reviewed retrospectively. From February 2002 to February 2010, 45 patients were diagnosed with FIGO stage IVB cervical cancer. Survival and toxicities were compared between the 13 patients with concomitant chemoradiotherapy (CCRT) with weekly cisplatin versus 20 patients with CCRT with 5-fluorouracil/cisplatin. Results: Initial treatment included weekly cisplatin-CCRT, 5-fluorouracil/cisplatin-CCRT, neoadjuvant chemotherapy, and radiotherapy with subsequent combination chemotherapy in 13, 20, 4, and 5 patients, respectively. Overall survival (OS) and PFS were 26.2 and 6.7 months, respectively. There was no statistical difference in OS ( p = 0.47) and PFS ( p = 0.64) between the weekly cisplatin-CCRT and 5-fluorouracil/cisplatin-CCRT groups; however, the incidence of anemia >grade 3 as an acute toxicity was higher in the 5-fluorouracil/cisplatin-CCRT chemotherapy regimen group than the weekly cisplatin-CCRT group ( p = 0.03). Acute toxicity >grade 2 showed a tendency to be higher in the 5-fluorouracil/cisplatin-CCRT group. Based on multivariate analysis, poor performance status was the only independent prognostic factor of OS ( p = 0.03, 9.77; 95% CI 1.3-73.3) and PFS ( p = 0.04, 9.58; 95% CI 1.14-81.26). Conclusions: CCRT using combination chemotherapeutic agents may not have survival advantage over single agent cisplatin-based CCRT. Further improvement in treatment is needed to increase survival outcomes and to decrease treatment-related toxicities in patients with stage IVB cervical cancer. [ABSTRACT FROM AUTHOR]

Background: This study was designed to determine whether serum HE4 is an independent prognostic factor in ovarian cancer patients. Methods: We measured HE4 in pretreatment serum samples from 80 women with epithelial ovarian cancer, using an enzyme-linked immunosorbent assay. The results were correlated with clinical data. Results: The median serum HE4 level in ovarian cancer patients was 98.7 (range, 80.3-222.8) pg/ml. Elevated serum HE4 levels before therapy significantly correlated with a poorer progression free survival (log-rank test, P = 0.017). Multivariate analysis revealed serum HE4 to be an independent prognostic factor for progression-free survival ( P = 0.036). In multivariate regression analysis, high serum HE4 levels significantly correlated with high tumor grade and serous histology ( P = 0.004 and 0.017). In addition, high serum HE4 levels were significantly associated with residual tumor size and operative time ( P = 0.003 and 0.033). Conclusions: Pretreatment serum HE4 seems to be an additional factor for predicting the outcome of patients with epithelial ovarian cancer. Due to its independence from established prognostic factors, serum HE4 may provide additional prognostic information. [ABSTRACT FROM AUTHOR]

During chronic injury a population of bipotent hepatic progenitor cells (HPCs) become activated to regenerate both cholangiocytes and hepatocytes. Here we show in human diseased liver and mouse models of the ductular reaction that Notch and Wnt signaling direct specification of HPCs via their interactions with activated myofibroblasts or macrophages. In particular, we found that during biliary regeneration, expression of Jagged 1 (a Notch ligand) by myofibroblasts promoted Notch signaling in HPCs and thus their biliary specification to cholangiocytes. Alternatively, during hepatocyte regeneration, macrophage engulfment of hepatocyte debris induced Wnt3a expression. This resulted in canonical Wnt signaling in nearby HPCs, thus maintaining expression of Numb (a cell fate determinant) within these cells and the promotion of their specification to hepatocytes. By these two pathways adult parenchymal regeneration during chronic liver injury is promoted. [ABSTRACT FROM AUTHOR]

Background: The goal of this study was to explore the necessity of extensive surgical procedures in patients who received neoadjuvant chemotherapy (NAC). Methods: We analyzed the surgical outcomes and frequency of extensive procedures required for maximal cytoreductive surgery after NAC and primary debulking surgery (PDS) in 256 women with advanced epithelial ovarian cancer. Results: NAC was performed in 116 of 256 women (45.3%). In NAC group, complete cytoreduction rate and optimal cytoreduction rate were 60.3 and 92.2%, respectively. Although the NAC group comprised patients with higher risk of suboptimal cytoreduction, complete cytoreduction rate was similar to that of PDS group (57.9%, P = .69). Moreover, blood loss and surgical complexity significantly reduced in NAC group ( P = .011 and .017). Extensive upper abdominal surgery (EUAS) was performed in 70 of 116 patients (60.3%) in the NAC group. The frequency of EUAS was similar between NAC and PDS group ( P = .60). Among NAC group, gross upper abdominal metastasis requiring EUAS was found in 51 patients (44%, 95% confidence interval = 35.3-53.1%). Conclusions: A significant proportion of patients who received NAC still have gross metastatic tumors requiring EUAS. Gynecologic oncologists should be familiar with EUAS and be ready to perform any required procedures together with multidisciplinary teams, even in the patients who have received NAC. [ABSTRACT FROM AUTHOR]

Objective: We aimed to determine the ideal cut-off of nadir serum CA-125 level for prediction of progression free survival. Methods: Among 267 patients who achieved complete remission after chemotherapy, the correlation between nadir CA-125 and progression free survival were compared among the subgroups classified according to the distribution of CA-125. The diagnostic odds ratio and area under the receiver operator characteristics curve were compared at various cut-off points. Results: The nadir CA-125 levels did not have prognostic value under 12 U/mL (to 75 percentile). In contrast, they were significantly correlated with progression free survival only when the CA-125 level was greater than 12, which was 75 percentile (p=0.034). In predicting progression free survival <6 and 12 months, the cut-off value of 18 (90 percentile) showed superior diagnostic performance over 10 or 12 U/mL. Compared with patients who showed nadir levels between 0 and 12 U/mL (0 to 75 percentile), those with nadir >18 U/mL showed a hazard ratio of 2.85 (95% confidence interval, 1.70 to 4.76; p<0.001); patients with nadir levels between 18 and 12 U/mL showed a the hazard ratio of 1.68 (95% confidence interval, 1.11 to 2.56; p=0.015) compared with those whose nadir levels were under 12 U/mL. Conclusion: The predictive power of the traditional cut-off of 10 U/mL to classify a risk group or to identify high risk patients was unsatisfactory. The optimal diagnostic performance was observed at the cut-off of 18 U/mL and this can be proposed to dichotomize cut-off values to predict outcomes among individual patients. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) DNA is considered as a hallmark of cervical cancer. We investigated whether persistent HPV DNA at the cervix is associated with local recurrence after radiotherapy in patients with locally advanced cervical cancer. A total of 156 patients with HPV-positive cervical cancer (International Federation of Gynecology and Obstetrics stage IB-IVB) treated with radiotherapy between July 2003 and December 2006 were analyzed. HPV DNA was measured prior to radiotherapy and after completion of radiotherapy. The results of HPV DNA test at postradiotherapy 1, 3, 6 and 12 months were analyzed individually for association with local recurrence-free survival (LRFS). In addition, the result of any last follow-up HPV test within 24 months postradiotherapy was defined as the overall status of HPV at 24 months and was also analyzed for association with LRFS. HPV DNA was cleared in 127 patients (81.4%) and persistent in 29 patients (18.6%) by 24 months. In 18 patients with local recurrences, 14 patients (78%) showed positive HPV tests at 1-3 months. Among the various time points analyzed, a positive HPV test at 3 months was the most accurate predictor of local recurrence. Multivariate analysis indicated that overall status of HPV at 24 months, low HPV viral load and histologic grade as being significantly related to poor LRFS. In HPV-positive cervical carcinoma treated primarily with radiotherapy, persistent HPV DNA within 24 months after treatment indicates a high risk of local recurrence. Diagnostic accuracy of HPV test was highest at 3 months. [ABSTRACT FROM AUTHOR]

Background: We aimed to determine whether the inclusion of additional cycles of carboplatin-paclitaxel is beneficial to patients with high posttreatment serum CA-125 levels. Methods: Among patients who achieved remission after six cycles of carboplatin-paclitaxel chemotherapy, those with CA-125 of 10-35 U/ml at the time of remission were divided into two groups (group A: six cycles of standard chemotherapy vs. group B: two or more additional cycles) and were analyzed. Results: Among the 436 patients with advanced epithelial ovarian cancer, 154 patients (46.8%) had CA-125 of 10-35 U/ml at the time of remission. Fifty-six patients (36.4%) received two or more cycles after the first six cycles of chemotherapy (group B). The addition of two or more cycles of chemotherapy did not improve the progression-free survival (p = 0.660). There was no statistical difference in the rates of CA-125 falling to <10 U/ml between the two groups (p = 0.256). Moreover, the degree of CA-125 decrease after six cycles of chemotherapy was similar regardless of the additional cycles (p = 0.656). Conclusion: The addition of two or more cycles of standard chemotherapy based on posttreatment CA-125 levels was not beneficial. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: To determine the accuracy of multi-detector CT (MDCT) compared with the surgical findings, such as peritoneal seeding and metastatic lymph nodes, in ovarian cancer patients. Methods: Fifty-seven FIGO stage IA-IV ovarian cancer patients, who underwent MDCT before primary surgery, were included in this study. Two radiologists evaluated the following imaging findings in consensus: the presence of nodular, plaque-like or infiltrative soft-tissue lesions in peritoneal fat or on the serosal surface; presence of ascites; parietal peritoneal thickening or enhancement; and small bowel wall thickening or distortion. We also evaluated the presence of lymph node metastases. To allow region-specific comparisons, the peritoneal cavity was divided into 13 regions and retroperitoneal lymph nodes were divided into 3 regions. Descriptive statistical data were thus obtained. Results: The MDCT sensitivity, specificity, positive predictive values, and negative predictive values were 45, 72, 46, and 72%, respectively, for detecting peritoneal seeding and 21, 90, 52, and 69%, respectively, for detecting lymph node metastasis. Conclusions: MDCT is moderately accurate for detecting peritoneal metastasis and lymph node metastasis in ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we identified p53 as a novel TCTP-interacting protein using TCTP as bait. Also, we determined the critical binding sites between TCTP and p53. To elucidate the functional consequence of the interaction, we developed the overexpression and inhibition system of TCTP and p53 expression. Overexpression of TCTP in lung carcinoma cells reversed p53 mediated apoptosis and inhibition of TCTP expression by small interfering RNA increased apoptosis of lung carcinoma cells. Moreover, it was observed that TCTP overexpression promotes degradation of p53. These results clearly indicate that the interaction between TCTP and p53 prevents apoptosis by destabilizing p53. Thus, TCTP acts as a negative regulator of apoptosis in lung cancer. Structured summary: MINT-8057107, MINT-8057116: p53 (uniprotkb:P04637) physically interacts (MI:0915) with TCTP (uniprotkb:P13693) by anti bait coimmunoprecipitation (MI:0006) MINT-8057141: TCTP (uniprotkb:P13693) physically interacts (MI:0915) with p53 (uniprotkb:P04637) by two hybrid pooling approach (MI:0398) MINT-8057126: p53 (uniprotkb:P04637) physically interacts (MI:0915) with TCTP (uniprotkb:P13693) by anti tag coimmunoprecipitation (MI:0007) MINT-8057160: TCTP (uniprotkb:P13693) physically interacts (MI:0915) with p53 (uniprotkb:P04637) by two hybrid (MI:0018) [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the maximum tolerated dose (MTD) and therapeutic efficacy of a newly developed CKD-602 topoisomerase I inhibitor and cisplatin in patients with recurrent epithelial ovarian cancer. CKD-602 (0.30 mg/m2 daily for 5 days) and cisplatin (60 mg/m2 on day 5) were administered to patients every 3 weeks with dose adjustment of CKD-602 by 0.05 mg/m2 daily until the MTD was reached. Dose-limiting toxicity was defined as grade ≥ 3 neutropenia or thrombocytopenia for more than 4 days or accompanied by fever ≥ 38.5°C, infection, hemorrhage, or transfusion; grade ≥ 3 nonhematological toxicity except for alopecia, nausea, and vomiting. We enrolled 26 patients with recurrent epithelial ovarian cancer who had measurable disease (MD) estimated by computed tomography scan ( n= 12) and nonmeasurable disease (NMD) evaluated by serum CA-125 levels ( n= 14). All patients received 188 cycles of CKD-602 and cisplatin with a median number of six cycles per patient (range, 2 to 12). MTD of CKD-602 was 0.30 mg/m2 daily. The overall response rate was 69.2% (18/26) with 58.3% (7/12) and 78.6% (11/14) in MD and NMD, respectively. Among the responsive patients, 14 were platinum sensitive (14/18, 77.7%) and four were platinum resistant (4/8, 50.0%). The most common toxicity was grade ≥ 3 neutropenia developing in 17 patients (65.4%) and 72 cycles (38.3%). Grade 3 nausea and anorexia were the most common gastrointestinal toxicities, developing in 15 cycles (8.0%) of four patients (15.4%) and 10 cycles (5.3%) of five patients (19.3%), respectively. The median disease-free interval was 6 months (range 0–26 months). CKD-602 at a concentration of 0.3 mg/m2 daily for 5 days and cisplatin at 60 mg/m2 on day 5 every 3 weeks showed high efficacy, with acceptable toxicity, against platinum-sensitive/resistant recurrent epithelial ovarian cancer. [ABSTRACT FROM AUTHOR]

Objectives. The symptoms associated with ovarian cancer are vague. Endometriosis, which causes dysmenorrhea and dyspareunia, is frequently detected along with ovarian clear cell carcinoma (OCCC). We have therefore evaluated the clinical manifestations of OCCC based on the co-existence of endometriosis. Methods. A retrospective analysis was conducted on 43 patients who had been treated for OCCC at the National Cancer Center between June 2000 and July 2007. Using medical records and the cancer registry, the clinical features and laboratory findings were analysed. Results. Endometriosis was identified in 16 (37.2%) of the 43 patients with OCCC. The main presenting symptoms included a hard, palpable mass (32.6%), and newly developed or an exacerbation of dysmenorrhea (32.6%) and dyspareunia (25.6%). Gastrointestinal symptoms, pelvic pain, and abdominal distension existed in nine (20.9%), eight (18.6%) and one (2.3%) of the patients, respectively. The symptoms did not differ statistically in patients with or without endometriosis. Thirty-seven percent (11/30) of the patients had a normal CA-125 level (<35 U/ml); 18.8% (3/16) of the patients without endometriosis and 57% (8/14) of the patients with endometriosis had normal levels of CA-125 (<35 U/ml). Nine of 16 (56.3%) patients with early stage OCCC had a normal CA-125 level. Conclusions. The main presenting symptoms in patients with OCCC include a hard, palpable mass, dysmenorrhea and dyspareunia, irrespective of co-existing endometriosis. A normal CA-125 level has limited value in excluding OCCC, especially in the early stages. [ABSTRACT FROM AUTHOR]

Background: The association of dietary glycemic index (GI) and glycemic load (GL) with the risk of cervical cancer has never been investigated. Thus, we aimed to find evidence of any association of GI and GL with the risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. Methods: In this hospital-based case-control study, we included 1340 women (670 controls and 262, 187 and 221 patients with CIN1, CIN2/3, and cervical cancer, respectively) from the Korean human papillomavirus cohort study. Completed demographic questionnaires and semi-quantitative food-frequency questionnaires were collected. The association of dietary GI and GL with CIN and cervical cancer was estimated using a logistic regression model. Results: The multivariate odds ratios (OR) of the highest compared with the lowest quintile of GL for CIN1 were 2.8 (95% confidence interval (CI) = 1.33–5.88). Dietary GI and GL were not associated with CIN2/3 and cervical cancer. Stratified analyses by body mass index (BMI) indicated a positive association between GI and GL and CIN 1 risk among women with a BMI (in kg/m2) <23 (OR = 2.94; 95% CI = 1.32–6.53; p for trend = 0.031 for GI and OR = 3.15; 95% CI = 1.53–6.52; p for trend = 0.013 for GL), but not among those with a BMI of ≥23. A stratification analysis by menopausal status showed that the highest quintile of GI and GL was significantly associated with the risk of CIN1 (OR = 2.91; 95% CI = 1.43–5.96; p for trend = 0.005) (OR = 2.96; 95% CI = 1.53–5.69; p for trend = 0.023) among premenopausal women. Also, in HPV positive women, dietary GL showed significant CIN1 risk (OR = 2.61; 95% CI = 1.09–6.24; p for trend = 0.087). Conclusion: Our case-control study supports the hypothesized associations of dietary GI and GL with increased risk of CIN1. Thus, the consumption of low GI and GL foods plays a significant role in the prevention of cervical carcinogenesis. [ABSTRACT FROM AUTHOR]

Embryonic-natural orifice transumbilical endoscopic surgery is currently used for adnexectomy or hysterectomy. Embryonic-natural orifice transumbilical endoscopic surgery for myomectomy with traction of two directional sutures in a 32-year-old woman enabled the minimal surgical approach for myomectomy and efficient and safe morcellation and retrieving of myoma. This novel surgical approach could be used as part of minimal surgery in the surgical management of myoma. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the effect of ovary preserving surgery in early International Federation of Obstetrics and Gynecology (FIGO) stage endometrial cancer patients. Methods: Medical records were retrospectively reviewed for 539 patients who were diagnosed with early stage endometrial cancer between Jan 2006 and Dec 2017. Patients were categorized into ovary preservation and ovary removal groups. Demographics, recurrence free survival (RFS), and five-year overall survival (OS) rate were compared, and the clinical factors affecting survival were evaluated by univariate and multivariate analysis. Results: The median follow-up period was 85 months (range, 6–142 months), and the median age was 52.7 years. The mean age was higher in the ovary removal group than in the ovary preservation group (54.4 vs 40.94 years; P < 0.001). The ovary preservation group showed an earlier FIGO stage than the ovary removal group (P = 0.0264). There was a greater incidence of adjuvant chemotherapy administration in the removal group. There were no statistical differences in other baseline characteristics. When comparing the RFS and OS rates, there were no statistical differences between the preservation and removal groups. (recurrence free rate 98.5% vs 92.7%, p = 0.4360, and 5-year survival rate 98.6% vs 93.0%, p = 0.0892, respectively). Endometrioid histology (p = 0.006) and post-operative adjuvant chemotherapy (p = 0.0062) were related to OS, and adjuvant chemotherapy (p < 0.001) and radiotherapy (p = 0.005) were related to RFS. Conclusions: Ovary preservation in early stage endometrial cancer is worth considering, as it does not affect survival in early stage endometrial cancer patients. [ABSTRACT FROM AUTHOR]

Cervical cancer remains one of the most prevalent cancers among females worldwide. Therefore, it is important to discover new biomarkers for early diagnosis of cervical intraepithelial neoplasia (CIN) and cervical cancer, preferably non-invasive ones. In the present study, we aimed to identify unique metabolic signatures for CINs and cervical cancers using global and targeted metabolomic profiling. Plasma samples (69 normal, 55 CIN1, 42 CIN2/3, and 60 cervical cancer) were examined by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS) coupled with multivariate statistical analysis. Metabolic pathways were analyzed using the integrated web-based tool MetaboAnalyst. A multivariate logistic regression analysis was conducted to evaluate the combined association of metabolites and human papillomavirus (HPV) status with the risk of cervical carcinogenesis. A total of 28 metabolites exhibiting discriminating levels among normal, CIN, and cervical cancer patients (Kruskal–Wallis test p < 0.05) were identified in the global profiling analysis. The pathway analysis showed significantly altered alanine, aspartate, and glutamate metabolic pathways (FDR p-value < 0.05) in both the discovery and validation phases. Seven metabolites (AMP, aspartate, glutamate, hypoxanthine, lactate, proline, and pyroglutamate) were discriminated between CINs and cervical cancer versus normal (area under the curve (AUC) value > 0.8). The levels of these metabolites were significantly high in patients versus normal (p < 0.0001) and were associated with increased risk of developing CIN2/3 and cervical cancer. Additionally, elevated levels of the seven metabolites combined with positive HPV status were correlated with substantial risk of cancer progression. These results demonstrated that metabolomics profiling is capable of distinguishing CINs and cervical cancers from normal and highlighted potential biomarkers for the early detection of cervical carcinogenesis. [ABSTRACT FROM AUTHOR]

Recent studies have reported the potential role of microbiomes in cervical disease. However, little is known about the microbiome composition and function in cervical carcinogenesis. We aimed to identify the compositional and functional alterations of cervical microbiomes in cases of cervical carcinogenesis of Korean women using shotgun metagenomic sequencing. In this study, using shotgun sequencing, we sequenced the cervical metagenomes of cervical intraneoplasia 2/3 (n = 17), cervical cancer (n = 12), and normal controls (n = 18) to identify the microbial abundances and enriched metabolic functions in cervical metagenomes. At the genus level, the microbiota of cervical cancer were differentially enriched with genera Alkaliphilus, Pseudothermotoga, and Wolbachia. Cervical intraepithelial neoplasia (CIN) 2/3 were enriched with Lactobacillus, Staphylococcus, and Candidatus Endolissoclinum. The normal group was enriched with Pseudoalteromonas and Psychrobacter. Further characterization of the functionalities of the metagenomes may suggest that six Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) that are involved in 10 pathways are associated with an increased risk of CIN2/3 and cervical cancer. Specifically, cervical metagenomes were enriched in the course of peptidoglycan synthesis and depleted by dioxin degradation and 4-oxalocrotonate tautomerase. The Cluster of Orthologous Groups (COG) category 'Defense mechanisms' was depleted in cervical cancer patients. Our findings based on shotgun metagenomic sequencing suggest that cervical microbiome community compositions and their metagenomics profiles differed between cervical lesions and normal subjects. Future studies should have larger sample sizes and/or aggregate their results to have sufficient power to detect reproducible and significant associations. [ABSTRACT FROM AUTHOR]