The human papillomavirus (HPV) E6 and E7 oncoproteins play important roles in cervical carcinogenesis through multiple mechanisms, including upregulation of cyclooxygenase-2 (COX-2), which has been shown to be involved in both carcinogenesis and cancer progression. To explore the role of E5 in cervical carcinogenesis, we herein investigated the effect of HPV 16 E5 on COX-2 expression. Our results revealed that E5 induced COX-2 expression through the epidermal growth factor receptor-signaling pathway, with nuclear factor-kappaB (NF-κB) and activator protein-1 (AP-1) acting as critical factors in E5-induced COX-2 expression. NF-κB inhibition blocked COX-2 expression more potently than inhibition of AP-1. Our findings collectively suggest that the HPV 16 E5 oncoprotein mediates cervical carcinogenesis at least in part via upregulation of COX-2 expression through NF-κB and AP-1, with NF-κB playing a larger role.

We compared the predictive and prognostic values of leukocyte differential counts, systemic inflammatory (SIR) markers and cancer antigen 125 (CA-125) levels, and identified the most useful marker in patients with ovarian clear cell carcinoma (OCCC). The study included 109 patients with OCCC who did not have any inflammatory conditions except endometriosis, and underwent primary debulking surgery between 1997 and 2012. Leukocyte differential counts (neutrophil, lymphocyte, monocyte, eosinophil, basophil, and platelet), SIR markers including neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), and platelet to lymphocyte ratio (PLR), and CA-125 levels were estimated to select potential markers for clinical outcomes. Among potential markers (neutrophil, monocyte, platelet, NLR, MLR, PLR, and CA-125 levels) selected by stepwise comparison, CA-125 levels were best at predicting advanced stage disease, suboptimal debulking and platinum-resistance (cut-off values, ≥ 46.5, ≥ 11.45, and ≥ 66.4 U/mL; accuracies, 69.4%, 78.7%, and 68.5%) while PLR ≥ 205.4 predicted non-complete response (CR; accuracy, 71.6%) most accurately. Moreover, PLR < 205.4 was an independent factor for the reduced risk of non-CR (adjusted odds ratio, 0.17; 95% confidence interval [CI], 0.04 to 0.69), and NLR < 2.8 was a favorable factor for improved progression-free survival (PFS; adjusted hazard ratio, 0.49; 95% CI, 0.25 to 0.99) despite lack of a marker for overall survival among the potential markers. CA-125 levels may be the most useful marker for predicting advanced-stage disease. Suboptimal debulking and platinum-resistance, and PLR and NLR may be most effective to predict non-CR and PFS in patients with OCCC.

BACKGROUND: Previously proposed criteria for preoperatively identifying endometrial cancer patients at low risk for lymph node metastasis remain to be verified. For this purpose, a prospective, multicenter observational study was performed.METHODS: Eligible patients with histologically confirmed endometrial cancer underwent magnetic resonance imaging (MRI) and serum cancer antigen 125 (CA 125) testing before surgery. The following criteria were used to identify low‐risk patients: 1) endometrioid‐type cancer, 2) no evidence of deep myometrial invasion on MRI, 3) no enlarged lymph nodes on MRI, 4) no suspicious metastasis out of the uterine corpus, and 5) serum CA 125 levels less than 35 U/mL. Systematic pelvic and/or para‐aortic lymphadenectomy was performed for all patients. The primary endpoint was estimation of the negative predictive value (NPV).RESULTS: From January 2012 to December 2014, 529 patients from 20 hospitals in 3 Asian countries were consecutively enrolled. According to our criteria, 272 patients (51.4%) were categorized into the low‐risk group. Fifty‐three of the 529 patients (10.0%) had lymph node metastases; these patients included 8 (2.9%) falsely categorized as low‐risk. The sensitivity and specificity of the criteria were 84.9% and 55.5%, respectively. The NPV of 97.1% was higher than the predefined target endpoint of 96%.CONCLUSIONS: The low‐risk criteria based on preoperative tests were confirmed to be reliable and accurate for identifying patients at low risk for lymph node metastasis. These criteria may facilitate patient counseling and surgical decision making. Cancer 2017;123:263–272. © 2016 American Cancer Society.

Background: The purpose of this study was to investigate the prognostic significance of serum sCD163 in patients with epithelial ovarian cancer. Methods: Preoperative serum samples from 55 patients with epithelial ovarian cancers were analyzed for sCD163 using a commercially available enzyme-linked immunosorbent assay kit. A Cox proportional hazard model was used to calculate hazard ratio (HR) and 95% confidence interval (CI) for disease-free survival (DFS) and overall survival (OS). Results: Median serum sCD163 levels were higher in patients with a high-grade tumor. High serum sCD163 levels (3.43 mg/l) were associated with poor prognostic factors such as advanced stage (p = 0.024) and positive peritoneal cytology (p = 0.015). Univariate survival analysis showed that elevated sCD163 levels were associated with short DFS (8.0 vs. 32.4 months, p = 0.04) and OS (19.7 vs. 40.0 months, p = 0.027). Multivariate survival analysis revealed that high serum sCD163 levels were negatively associated with DFS (HR 3.1, 95% CI 1.2-8.1, p = 0.039). Conclusions: Our study shows that elevated serum sCD163 levels were associated with poor prognosis in patients with ovarian cancer. Impact: The prognostic significance of serum sCD163 in patients with epithelial ovarian cancer is described.