Decoding temporal heterogeneity in NSCLC through machine learning and prognostic model construction.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a prevalent and heterogeneous disease with significant genomic variations between the early and advanced stages. The identification of key genes and pathways driving NSCLC tumor progression is critical for improving the diagnosis and treatment outcomes of this disease. METHODS: In this study, we conducted single-cell transcriptome analysis on 93,406 cells from 22 NSCLC patients to characterize malignant NSCLC cancer cells. Utilizing cNMF, we classified these cells into distinct modules, thus identifying the diverse molecular profiles within NSCLC. Through pseudotime analysis, we delineated temporal gene expression changes during NSCLC evolution, thus demonstrating genes associated with disease progression. Using the XGBoost model, we assessed the significance of these genes in the pseudotime trajectory. Our findings were validated by using transcriptome sequencing data from The Cancer Genome Atlas (TCGA), supplemented via LASSO regression to refine the selection of characteristic genes. Subsequently, we established a risk score model based on these genes, thus providing a potential tool for cancer risk assessment and personalized treatment strategies. RESULTS: We used cNMF to classify malignant NSCLC cells into three functional modules, including the metabolic reprogramming module, cell cycle module, and cell stemness module, which can be used for the functional classification of malignant tumor cells in NSCLC. These findings also indicate that metabolism, the cell cycle, and tumor stemness play important driving roles in the malignant evolution of NSCLC. We integrated cNMF and XGBoost to select marker genes that are indicative of both early and advanced NSCLC stages. The expression of genes such as CHCHD2, GAPDH, and CD24 was strongly correlated with the malignant evolution of NSCLC at the single-cell data level. These genes have been validated via histological data. The risk score model that we established (represented by eight genes) was ultimately validated with GEO data. CONCLUSION: In summary, our study contributes to the identification of temporal heterogeneous biomarkers in NSCLC, thus offering insights into disease progression mechanisms and potential therapeutic targets. The developed workflow demonstrates promise for future applications in clinical practice.

Phospholipase D1 promotes cervical cancer progression by activating the RAS pathway.

This study aimed to further investigate the effect of PLD1 on the biological characteristics of human cervical cancer (CC) cell line, CASKI and the potential related molecular mechanism. CRISPR/Cas9 genome editing technology was used to knock out the PLD1 gene in CASKI cells. Cell function assays were performed to evaluate the effect of PLD1 on the biological function of CASKI cells in vivo and in vitro. A PLD1-overexpression rescue experiment in these knockout cells was performed to further confirm its function. Two PLD1-knockout CASKI cell lines (named PC-11 and PC-40, which carried the ins1/del4 mutation and del1/del2/ins1 mutation, respectively), were constructed by CRISPR/Cas9. PLD1 was overexpressed in these knockout cells (named PC11-PLD1 and PC40-PLD1 cells), which rescued the expression of PLD1 by approximately 71.33% and 74.54%, respectively. In vivo, the cell function assay results revealed that compared with wild-type (WT)-CASKI cells, the ability of PC-11 and PC-40 cells to proliferate, invade and migrate was significantly inhibited. The expression of H-Ras and phosphorylation of Erk1/2 (p-Erk1/2) was decreased in PC-11 and PC-40 cells compared with WT-CASKI cells. PC-11 and PC-40 cells could sensitize CASKI cells to cisplatin. More importantly, the proliferation, migration and invasion of PC11-PLD1 and PC40-PLD1 cells with PLD1 overexpression were significantly improved compared with those of the two types of PLD1 knockout cells. The sensitivity to cisplatin was decreased in PC11-PLD1 and PC40-PLD1 cells compared with PC-11 and PC-40 cells. In vivo, in the PC-11 and PC-40 tumour groups, tumour growth was significantly inhibited and tumour weight (0.95 ± 0.27 g and 0.66 ± 0.43 g vs. 1.59 ± 0.67 g, p = 0.0313 and 0.0108) and volume (1069.41 ± 393.84 and 1077.72 mm3 ± 815.07 vs. 2142.94 ± 577.37 mm3 , p = 0.0153 and 0.0128) were significantly reduced compared to those in the WT-CASKI group. Tumour differentiation of the PC-11 and PC40 cells was significantly better than that of the WT-CASKI cells. The immunohistochemistry results confirmed that the expression of H-Ras and p-Erk1/2 was decreased in PC-11 and PC-40 tumour tissues compared with WT-CASKI tumour tissues. PLD1 promotes CC progression by activating the RAS pathway. Inhibition of PLD1 may serve as an attractive therapeutic modality for CC.

DUSP7 inhibits cervical cancer progression by inactivating the RAS pathway.

To determine the differentially expressed proteins (DEPs) between paired samples of cervical cancer (CC) and paracancerous tissue by quantitative proteomics and to examine the effects of DUSP7 expression on the tumorigenesis and progression of CC. Proteomic profiles of three paired samples of CC and paracancerous tissue were quantitatively analysed to identify DEPs. The relationship between DEP expression and patient clinicopathological characteristics and prognosis was evaluated. The effects of the selected DEPs on CC progression were examined in SIHA cells. A total of 129 DEPs were found. Western blot and immunohistochemistry (IHC) staining analyses confirmed the results from quantitative proteomic analysis showing that the selected DEP, HRAS, P-ERK1/2, and PLD1 levels were increased, whereas the DUSP7 level was decreased in CC tissue compared with the paired normal paracancerous tissues. The IHC results from the CC TMA analysis showed that the decreased expression of DUSP7 (p = 0.045 and 0.044) was significantly associated with a tumour size >2 cm and parametrial infiltration. In addition, the decreased expression of DUSP7 and increased expression of p-ERK1/2 were adversely related to patient relapse (p = 0.003 and 0.001) and survival (p = 0.034 and 0.006). The expression of HRAS and p-ERK1/2 was decreased in DUSP7-SIHA cells compared with NC-SIHA cells (p = 0.0003 and 0.0026). Biological functions in vitro, including invasion, migration and proliferation and tumour formation in vivo were decreased in DUSP7-SIHA cells (all p < 0.05) but increased in shDUSP7-SIHA cells (all p < 0.05). DUSP7 inhibits cervical cancer progression by inactivating the RAS pathway.

Multi-omics mapping of human papillomavirus integration sites illuminates novel cervical cancer target genes.

BACKGROUND: Integration of human papillomavirus (HPV) into the host genome is a dominant feature of invasive cervical cancer (ICC), yet the tumorigenicity of cis genomic changes at integration sites remains largely understudied. METHODS: Combining multi-omics data from The Cancer Genome Atlas with patient-matched long-read sequencing of HPV integration sites, we developed a strategy for using HPV integration events to identify and prioritise novel candidate ICC target genes (integration-detected genes (IDGs)). Four IDGs were then chosen for in vitro functional studies employing small interfering RNA-mediated knockdown in cell migration, proliferation and colony formation assays. RESULTS: PacBio data revealed 267 unique human-HPV breakpoints comprising 87 total integration events in eight tumours. Candidate IDGs were filtered based on the following criteria: (1) proximity to integration site, (2) clonal representation of integration event, (3) tumour-specific expression (Z-score) and (4) association with ICC survival. Four candidates prioritised based on their unknown function in ICC (BNC1, RSBN1, USP36 and TAOK3) exhibited oncogenic properties in cervical cancer cell lines. Further, annotation of integration events provided clues regarding potential mechanisms underlying altered IDG expression in both integrated and non-integrated ICC tumours. CONCLUSIONS: HPV integration events can guide the identification of novel IDGs for further study in cervical carcinogenesis and as putative therapeutic targets.

A novel MtHSP70-FPR1 fusion protein enhances cytotoxic T lymphocyte responses to cervical cancer cells by activating human monocyte-derived dendritic cells via the p38 MAPK signaling pathway.

OBJECTIVE: To evaluate the potential effects of recombinant mycobacterium tuberculosis heat shock protein 70-formyl peptide receptor 1 (MtHSP70-FPR1) fusion protein on human monocyte-derived dendritic cell (moDC) maturation; cytotoxic T lymphocyte (CTL) responses to cervical cancer (CC) cells; and the roles of the p38 MAPK, ERK, and JNK pathways in its transition. METHODS: Monocytes were positively selected with a MACS column with antiCD14 antibody-conjugated microbeads from umbilical cord blood. MoDCs were stimulated with MtHSP70-FPR1, MtHSP70, a mix of MtHSP70 and FPR1, FPR1, or phosphate buffer solution (PBS) as control. Flow cytometry was used to analyze the surface molecule expression of moDCs and IFN-γ-producing CD8+ T cells. T cell proliferation was assessed using [3][H]-thymidine assays. The cytotoxicity of moDC-activated T cells against CC cells was evaluated by MTT assays. Cytokine production was determined by enzyme-linked immunosorbent assay. Western blotting was used to investigate protein expression. RESULTS: Compared with MtHSP70, MtHSP70 + FPR1, FPR1, or PBS-mediated moDCs, MtHSP70-FPR1-pulsed moDCs expressed higher levels of CD80, CD86, CD83, HLA-DR, and CCR7; secreted more IL-12p70, TNF-ɑ and IL-1ß; and elicited stronger CTL priming and proliferation, resulting in an effective, HLA-I-dependent killing effect on CC cells. The p38 MAPK, ERK, and JNK pathways were all activated in MtHSP70-FPR1-mediated moDC maturation, but the p38 MAPK pathway played a vital role. CONCLUSIONS: The excellent capability of MtHSP70-FPR1 fusion protein to induce phenotypical and functional maturation of moDCs and CC-specific CTL responses partly illustrates the potential clinical benefits of DC-based immunotherapy for CC.

Sexual Function and Quality of Life Among Patients With Endometrial Cancer After Surgery.

OBJECTIVE: The aim of this study was to evaluate the sexual function and quality of life (QOL) and identify their associated factors in survivors of endometrial cancer. METHODS: The participants in this study were survivors of endometrial cancer who visited the gynecological outpatient department for routine surveillance from June 2014 to May 2015. The QOL and sexual function were measured using the Functional Assessment of Cancer Therapy-General (FACT-G) and Female Sexual Function Index questionnaires. A score less than 26.55 was defined as female sexual dysfunction (FSD). Multivariate analysis and logistic regression were performed to identify the factors associated with QOL and sexual function. RESULTS: A total of 118 women completed the questionnaires. The results revealed that 68.6% of the patients had FSD and that 55.9% of the patients never had sexual intercourse with their partners after surgery. Age, followed by time after surgery, radiotherapy, and consultation, was significantly correlated with FSD. The median score of the FACT-G was 86 (range, 41-108). Chemotherapy and marital status were found to significantly impair physical and social/family well-being, respectively (P < 0.05), and monthly income was identified as a factor that significantly affected the total FACT-G scores. CONCLUSION: The risk factors associated with FSD and QOL need to be studied in greater detail. Prospective researches that evaluate the effects of clinical psychological intervention on sexual function may be needed in the future.

Real-time auto-segmentation of the ureter in video sequences of gynaecological laparoscopic surgery.

BACKGROUND: Ureteral injury is common during gynaecological laparoscopic surgery. Real-time auto-segmentation can assist gynaecologists in identifying the ureter and reduce intraoperative injury risk. METHODS: A deep learning segmentation model was crafted for ureter recognition in surgical videos, utilising 3368 frames from 11 laparoscopic surgeries. Class activation maps enhanced the model's interpretability, showing its areas. The model's clinical relevance was validated through an End-User Turing test and verified by three gynaecological surgeons. RESULTS: The model registered a Dice score of 0.86, a Hausdorff 95 distance of 22.60, and processed images in 0.008 s on average. In complex surgeries, it pinpointed the ureter's position in real-time. Fifty five surgeons across eight institutions found the model's accuracy, specificity, and sensitivity comparable to human performance. Yet, artificial intelligence experience influenced some subjective ratings. CONCLUSIONS: The model offers precise real-time ureter segmentation in laparoscopic surgery and can be a significant tool for gynaecologists to mitigate ureteral injuries.

Clinical analysis and artificial intelligence survival prediction of serous ovarian cancer based on preoperative circulating leukocytes.

Circulating leukocytes are an important part of the immune system. The aim of this work is to explore the role of preoperative circulating leukocytes in serous ovarian carcinoma and investigate whether they can be used to predict survival prognosis. Routine blood test results and clinical information of patients with serous ovarian carcinoma were retrospectively collected. And to predict survival according to the blood routine test result the decision tree method was applied to build a machine learning model.The results showed that the number of preoperative white blood cells (p = 0.022), monocytes (p < 0.001), lymphocytes (p < 0.001), neutrophils (p < 0.001), and eosinophils (p < 0.001) and the monocyte to lymphocyte (MO/LY) ratio in the serous ovarian cancer group were significantly different from those in the control group. These factors also showed a correlation with other clinicopathological characteristics. The MO/LY was the root node of the decision tree, and the predictive AUC for survival was 0.69. The features involved in the decision tree were the MO/LY, differentiation status, CA125 level, neutrophils (NE,) ascites cytology, LY% and age.In conclusion, the number and percentage of preoperative leukocytes in patients with ovarian cancer is changed significantly compared to those in the normal control group, as well as the MO/LY. A decision tree was built to predict the survival of patients with serous ovarian cancer based on the CA125 level, white blood cell (WBC) count, presence of lymph node metastasis (LNM), MO count, the MO/LY ratio, differentiation status, stage, LY%, ascites cytology, and age.

An Applicable Machine Learning Model Based on Preoperative Examinations Predicts Histology, Stage, and Grade for Endometrial Cancer.

Purpose: To build a machine learning model to predict histology (type I and type II), stage, and grade preoperatively for endometrial carcinoma to quickly give a diagnosis and assist in improving the accuracy of the diagnosis, which can help patients receive timely, appropriate, and effective treatment. Materials and Methods: This study used a retrospective database of preoperative examinations (tumor markers, imaging, diagnostic curettage, etc.) in patients with endometrial carcinoma. Three algorithms (random forest, logistic regression, and deep neural network) were used to build models. The AUC and accuracy were calculated. Furthermore, the performance of machine learning models, doctors' prediction, and doctors with the assistance of models were compared. Results: A total of 329 patients were included in this study with 16 features (age, BMI, stage, grade, histology, etc.). A random forest algorithm had the highest AUC and Accuracy. For histology prediction, AUC and accuracy was 0.69 (95% CI=0.67-0.70) and 0.81 (95%CI=0.79-0.82). For stage they were 0.66 (95% CI=0.64-0.69) and 0.63 (95% CI=0.61-0.65) and for differentiation grade 0.64 (95% CI=0.63-0.65) and 0.43 (95% CI=0.41-0.44). The average accuracy of doctors for histology, stage, and grade was 0.86 (with AI) and 0.79 (without AI), 0.64 and 0.53, 0.5 and 0.45, respectively. The accuracy of doctors' prediction with AI was higher than that of Random Forest alone and doctors' prediction without AI. Conclusion: A random forest model can predict histology, stage, and grade of endometrial cancer preoperatively and can help doctors in obtaining a better diagnosis and predictive results.

Human monocytes differentiate into tumor-associated macrophages upon SKOV3 cells coculture and/or lysophosphatidic acid stimulation.

BACKGROUND: Serous ovarian carcinoma is the most common type of ovarian carcinoma. Tumor-associated macrophages (TAMs) promote ovarian cancer progression. Most macrophages are generated by monocyte differentiation. Lysophosphatidic acid (LPA) levels are high in blood, tissues and ascites of patients with ovarian cancer. This study investigated whether human monocytes can directly differentiate into TAMs in the serous ovarian carcinoma microenvironment. METHODS: Human monocytes were isolated and purified from umbilical cord blood. A serous ovarian carcinoma-like microenvironment was generated by coculturing monocytes and SKOV3 cells in 0.4-µm-pore-size Transwell chambers. Additionally, the effect of LPA was assessed. The two cultured cell types and supernatants were evaluated. RESULTS: The morphology and function of monocytes cocultured with SKOV3 cells and/or stimulated with LPA were significantly changed compared with those of non-stimulated monocytes. The CD14 + CD163 + and CD206 + phenotype indicated that stimulated cells were TAMs. The induced cells promoted SKOV3 cell proliferation and invasion, further proving that they were TAMs. The level of the cytokine interleukin-6R in the supernatant was significantly elevated in the treatment groups compared to the control monocyte group. Pathway enrichment analysis of ELISA results showed a strong influence of interleukin-6 family signaling, especially the JAK-STAT signaling pathway, further confirming the importance of IL-6R. CONCLUSION: Monocytes can differentiate into TAMs under coculture with SKOV3 cells and/or LPA stimulation. The induced TAMs promote SKOV3 cell proliferation and invasion. The cytokine receptor IL-6sR and the JAK-STAT signaling pathway play an important role in the differentiation of monocytes into TAMs.

Potential interaction between lysophosphatidic acid and tumor-associated macrophages in ovarian carcinoma.

Ovarian carcinoma is the deadliest type of gynecological cancer. The unique tumor microenvironment enables specific and efficient metastasis, weakens immunological monitoring, and mediates drug resistance. Tumor associated macrophages (TAMs) are a crucial part of the TME and are involved in various aspects of tumor behavior. Lysophosphatidic acid (LPA) is elevated in the blood of ovarian carcinoma patients, as well as in the tumor tissues and ascites, which make it a useful biomarker and a potential therapeutic target. Recent studies have shown that LPA transforms monocytes into macrophages and regulates the formation of macrophages through the AKT/mTOR pathway, and PPAR γ is a major regulator of LPA-derived macrophages. In addition, TAMs synthesize and secrete LPA and express LPA receptor (LPAR) on the surface. With these data in mind, we hypothesize that LPA can convert monocytes directly into TAMs in the microenvironment of ovarian cancer. LPA may mediate TAM formation by activating the PI3K/AKT/mTOR signaling pathway through LPAR on the cell surface, which may also affect the function of PPAR γ, leading to increased LPA production by TAMs. Thus, LPA and TAMs form a vicious circle that affects the malignant behavior of ovarian cancer.

The Surgical Morbidity And Oncological Outcome Of Total Laparoscopic Radical Trachelectomy Versus Total Laparoscopic Radical Hysterectomy For Early Stage Cervical Cancer: A Retrospective Study With 11-Year Follow-Up.

OBJECTIVE: The objective of this study was to evaluate the surgical morbidity and oncological outcome of total laparoscopic radical trachelectomy (TLRT) and total laparoscopic radical hysterectomy (TLRH) in patients with early-stage cervical cancer. METHODS: We performed a retrospective study to compare the outcomes of patients with stage IB1 cervical cancer who underwent TLRT to patients treated with TLRH from January 2005 to December 2016. RESULTS: Forty-six patients underwent TLRT and 73 patients underwent TLRH between January 2005 and December 2016. The median age was 30 (19-40) years for TLRT group compared to 43 (31-65) years for TLRH group. No significant difference was found for the tumor size, histology, and pathology grade between TLRT group and TLRH group. In the TLRT group, the median operative time was 200 mins (range, 150-360 mins) and the median blood loss was 200 mL (range, 50-400mL). In the TLRH group, the median operative time was 240 mins (range, 180-380) and the median blood loss was 250mL (range, 10-1500mL). The median follow-up time was 80 months for TLRT group and 72 months for TLRH group. No patient in TLRT group developed recurrence. However, there were 2 recurrences diagnosed in the TLRH group. CONCLUSION: TLRT appears to have equal surgical morbidity and oncological outcome to TLRH in stage IB1 cervical cancer. Intraoperative complications did not differ significantly between these two groups. However, postoperative complications were fewer observed in TLRT. Because of the natural limitations of the retrospective study, the clinical value should be confirmed by multi-institutional prospective trial in the future.

Prognostic values of long noncoding RNA PVT1 in various carcinomas: An updated systematic review and meta-analysis.

Cancers have been a worldwide health problem with a high mortality rate, but ideal biomarkers are not available to effectively screen and diagnose patients. Currently, an increasing number of long noncoding RNAs have been reported to be abnormally expressed in human carcinomas and play a vital role in tumourigenesis. Plasmacytoma variant translocation 1 (PVT1) is upregulated in various carcinomas, and its overexpression is associated with poor survival in cancer patients. We conduct an updated meta-analysis to determine its potential in prognosis for tumours. In total, 14 studies comprising 2435 patients were enrolled according to Reporting Recommendations for Tumour Marker Prognostic Studies guidelines. High PVT1 expression indicated poor overall survival (hazard ratio [HR] = 1.98, 95% confidence interval [CI]: 1.62-2.42, P < 0.00001) and disease-free survival (HR = 1.63, 95% CI: 1.45-1.84, P < 0.00001). Additionally, increased PVT1 expression was positively associated with lymphatic node metastasis (odd ratio [OR] = 2.87, 95% CI: 1.66-4.96, P = 0.0002), distant metastasis (OR = 2.47, 95% CI: 1.74-3.50, P < 0.00001), advanced tumour-node-metastasis stages (OR = 2.59, 95% CI: 1.38-4.88, P = 0.003). New findings highlight that PVT1 acts as competing RNA to microRNAs to protect mRNAs from miRNAs repression. Therefore, we also discuss PVT1-related microRNAs and their interaction in tumourigenesis. In conclusion, PVT1 may be a potential biomarker of poor prognosis for patients with different cancer types.

Quality of life and sexuality in disease-free survivors of cervical cancer after radical hysterectomy alone: A comparison between total laparoscopy and laparotomy.

The aim of the present study was to evaluate the possible differences between total laparoscopy and laparotomy regarding their impact on postoperative quality of life and sexuality in disease-free cervical cancer survivors who received radical hysterectomy (RH) and/or lymphadenectomy alone and were followed for >1 year.We reviewed all patients with cervical cancer who had received surgical treatment in our hospital between January 2001 and March 2014. Consecutive sexually active survivors who received RH and/or lymphadenectomy for early stage cervical cancer were enrolled and divided into 2 groups based on surgical approach. Survivors were interviewed and completed validated questionnaires, including the European Organization for Research Treatment of Cancer Quality-of-Life Core Questionnaire including 30 items, the Cervical Cancer-Specific Module of European Organization for Research Treatment of Cancer Quality-of-Life Questionnaire including 24 items (EORTC QLQ-CX24), and the Female Sexual Function Index (FSFI).In total, 273 patients with histologically confirmed cervical cancer were retrospectively reviewed. However, only 64 patients had received RH and/or lymphadenectomy alone; 58 survivors meeting the inclusion criteria were enrolled, including 42 total laparoscopy cases and 16 laparotomy cases, with an average follow-up of 46.1 and 51.2 months, respectively. The survivors in the 2 groups obtained good and similar scores on all items of the European Organization for Research Treatment of Cancer Quality-of-Life Core Questionnaire including 30 items and Cervical Cancer-Specific Module of European Organization for Research Treatment of Cancer Quality-of-Life Questionnaire including 24 items, without significant differences after controlling for covariate background characteristics. To the date of submission, 21.4% (9/42) of cases in the total laparoscopy group and 31.2% (5/16) of cases in the laparotomy group had not resumed sexual behavior after RH. Additionally, the scores on the FSFI items were comparable between the 2 groups; however, the total FSFI scores were 19.7 and 17.4 for total laparoscopy and laparotomy survivors, respectively, both of which were less than the validated cutoff value of 26.6 for diagnosing female sexual dysfunction.Disease-free cervical cancer survivors after RH and/or lymphadenectomy were able to cope well, although RH could greatly impair females' sexual function regardless of surgical approach. Moreover, the long-term quality of life and sexual function of survivors seemed to be independent of the surgical approach chosen. Randomized controlled and longitudinal trials with larger populations are needed to better compare these issues between patients receiving laparoscopy and laparotomy.

Prevalence of Human Papillomavirus Genotypes Among Women With High-Grade Cervical Lesions in Beijing, China.

The aim of the study is to investigate the prevalence of high-risk human papillomavirus (hr-HPV) genotypes among Han women with high-grade cervical lesions in Beijing, China.Cervical cell specimens from patients with histopathologically confirmed cervical lesions at 7 hospitals in Beijing were examined with a validated HPV kit for 13 hr-HPV genotypes during the study period. The patients were divided into a low-grade cervical lesions group (cervical intraepithelial neoplasia grade 1, CIN1) and a high-grade cervical lesions group (CIN2+, including cervical intraepithelial neoplasia grade 2, CIN2; cervical intraepithelial neoplasia grade 3, CIN3; squamous cervical cancer, SCC; and adenocarcinoma of the cervix, ACC) based on the histopathology results.A total of 2817 eligible patients were enrolled, including 610 cases identified as CIN1 and 2207 as CIN2+. The hr-HPV positive rates in the CIN1 and CIN2+ groups were 78.2% (477/610) and 93.3% (2060/2207), respectively. The most frequently detected genotypes were HPV16, 58, 52 and18 in the CIN1 group and HPV16, 58, 33, and 52 in the CIN2+ group, in descending order of prevalence. In addition, the prevalence of HPV18 among the patients with ACC was 28.6% (14/49), significantly >7.2% (54/752) prevalence among the SCC patients (P < 0.001). Additionally, significantly more women in the CIN2+ group had multiple infections compared with those in the CIN1 group (38.1% and 24.9%, respectively; P < 0.001). However, as the cervical lesion grade increased, the prevalence of multiple hr-HPV infections gradually deceased to 44.2% in the CIN2 patients, 36.7% in the CIN3 patients, and 35.3% in the cervical cancer (CC) patients, which included SCC and ACC patients. In cases of multiple hr-HPV infections in the CIN2+ group, double infections accounted for ∼76.6%, and HPV16+58, HPV16+52, and HPV16+18 were the most common combinations, in descending order. The most frequent combination for triple infections was HPV16+58+31, with a rate of 4.2%. The highest positive rate occurred in the ≤24 year-old group for all types of cervical lesions.The prevalence of HPV genotypes in the targeted population with high-grade cervical lesions differs from that of other countries. This information could be helpful for the prevention of CC in Beijing, China.

The prognostic value of pretreatment CA-125 levels and CA-125 normalization in ovarian clear cell carcinoma: a two-academic-institute study.

OBJECTIVES: The present study investigated the clinical implications of pretreatment carbohydrate antigen 125 (CA-125) levels and CA-125 normalization in patients with ovarian clear cell carcinoma (CCC), and it provides useful information for the improvement of monitoring strategies for this lethal disease. METHODS: The medical records of patients with ovarian CCC who had undergone primary staging surgery or cytoreductive surgery followed by systemic chemotherapy were retrospectively reviewed. A range of clinico-pathological parameters were collected and examined. RESULTS: A total of 375 women were included in the analysis. FIGO stage (p < 0.001) was identified as the only significant prognostic factor for relapse. Residual tumor and advanced stage (p = 0.001 and p < 0.001, respectively) were identified as independent adverse factors for survival. The potential risk factors associated with elevated pretreatment CA-125 levels included advanced-stage disease, positive residual tumors and negative endometriosis (p < 0.001, p = 0.001 and p <0.001, respectively). Pretreatment CA-125 levels were not associated with relapse-free survival (RFS) or overall survival (OS) (p = 0.060 and p = 0.176, respectively). CA-125 normalization after chemotherapy exhibited a positive linear correlation with advanced stage (r = 0.97, p = 0.001) and residual tumor (r = 0.81, p = 0.027) and a negative relationship with 5-year RFS (r = -0.97, p = 0.002) and 5-year OS (r = -0.97, p= 0.001). Patients with CA-125 levels that normalized before cycle 2 of chemotherapy had a similar prognosis as patients whose CA-125 levels normalized prior to chemotherapy (RFS: p = 0.327; OS: p = 0.654). By contrast, patients with CA-125 levels that normalized after cycle 2 of chemotherapy or never normalized were significantly more likely to experience disease progression. CONCLUSIONS: Pretreatment CA-125 levels are not very useful for predicting clinical outcome. CA-125 levels following treatment are a valid indicator for treatment monitoring. CA-125 normalization after the completion of cycle 1 of chemotherapy represents a distinct inflection point for decreased RFS and OS.

Accuracy of conization procedure for predicting pathological parameters of radical hysterectomy in stage Ia2-Ib1 (≤2 cm) cervical cancer.

The accuracy of conization for the prediction of radical hysterectomy (RH) pathological variables in patients with stage Ia2 to Ib1 (≤2 cm) cervical cancer was retrospectively evaluated in the present study. Endocervical or deep resection margin (RM) involvement in the conization specimens was found to be independently associated with residual disease in the hysterectomy specimens (P < 0.001, = 0.003, respectively). When a tumor width of >20 mm in the final RH pathology analysis was predicted by a tumor width of >2 mm or involvement of endocervical or deep RMs in the conization specimens, the sensitivity and negative predictive value (NPV) of conization were 98.2% and 95.2%, respectively. In addition, when deep stromal invasion in the final RH pathology analysis was predicted by deep stromal invasion or involvement of the endocervical or deep RMs in the conization specimens, the sensitivity and NPV of conization were 98.4% and 95.8%, respectively. The sensitivity and NPV of this prediction model for identifying LVSI in the final RH pathology analysis were both 100%. These findings suggest that conization variables and endocervical and deep resection margin statuses can be analyzed to effectively predict RH pathological parameters.

Total Laparoscopic Versus Laparotomic Radical Hysterectomy and Lymphadenectomy in Cervical Cancer: An Observational Study of 13-Year Experience.

This article aims to review our 13-year experience in the treatment of patients with cervical cancer by comparing total laparoscopic radical hysterectomy and lymphadenectomy with laparotomy.We reviewed all patients undergoing total laparoscopic or laparotomic radical hysterectomy and lymphadenectomy because of cervical cancer between 2001 and 2014 in our hospital.In total, 154 eligible patients with International Federation of Gynecology and Obstetrics Ia-IIb were enrolled, including 106 patients undergoing total laparoscopic procedure and 48 patients undergoing laparotomic procedure. In the present study, patients in total laparoscopy group were associated with superior surgical outcomes, such as significantly lower blood transfusion compared to those in laparotomy group. Furthermore, patients had significantly lower postoperative complication rate in total laparoscopy group compared with that in laparotomy group (24.5% vs 52.1%) (P = 0.001). Three patients (2.8%) in total laparoscopy group had unplanned conversion to laparotomy. Disease-free survival rates were 89.7% and 88.9% in total laparoscopy and laparotomy groups (P = 0.39), respectively, and overall survival rates were 90.2% in total laparoscopy group and 91.3% in laparotomy group (P = 0.40).Total laparoscopic procedure is a surgically and oncologically safe and reliable alternative to laparotomic procedure in the treatment for cervical cancer.