Expression of HIF-1α is a predictive marker of the efficacy of neoadjuvant chemotherapy for locally advanced cervical cancer.

Platinum-based, arterial infusion chemotherapy as a neoadjuvant chemotherapy (NACT) followed by hysterectomy may be efficient for the treatment of locally advanced cervical cancer and improve prognosis. It is important to predict whether the NACT would be effective before it is launched. Hypoxia inducible factor-1α (HIF-1α) is the master transcriptional regulator of the cellular response to altered oxygen concentration. HIF-1α protein expression is elevated in numerous human malignancies, contributes to poor disease outcome, and has been reported to induce tumorigenesis and chemoresistance. In the present study, patients with International Federation of Gynecology and Obstetrics stage IIB-IIIB cervical cancer (n=59) between 2008 and 2014 were assessed for HIF-1α expression by immunohistochemistry. Tumor samples were obtained by biopsy before any treatment. A double-path chemotherapy regimen, paclitaxel (intravenous) plus cisplatin (intra-arterial injection into the uterine region), was used as NACT. The patients were then separated into two groups according to NACT response: One group comprised patients with NACT, for whom the response to treatment was efficient resulting in complete/partial remission of the tumor (CR + PR group; n=52), the other group contained patients with NACT, for whom the result of the treatment was a stable/progressive disease (SD + PD group; n=7). HIF-1α expression was tested in paraffin-embedded sections using immunohistochemistry. HIF-1α expression was significantly higher in the SD + PD group compared with the CR + PR group (P=0.029). The overall survival time was significantly longer in the CR + PR group compared with the SD + PD group (P<0.001). When the patients were divided into two groups based on HIF-1α expression levels. Low (weighted score ≤4, n=39) and high (weighted score ≥6, n=20) expression level groups; the low HIF-1α expression group was significantly more susceptible to NACT treatment (P=0.025). Cox hazard analysis revealed that a high level of HIF-1α expression and lymph node metastases were significant independent predictors of poor overall survival (P=0.025, HR=6.354; P=0.020, HR=6.909, respectively). These results indicated that the expression of HIF-1α may be able to predict the efficiency of NACT and may be considered an independent prognostic factor for stage IIB-IIIB cervical cancer.

Prevalence and Determinants of High-risk HPV Infection among 11549 Women from an Opportunistic Screening in Hubei Province.

High-risk human papillomavirus (hrHPV) infection plays an important role in the development of cervical intraepithelial neoplasia and cervical cancer. A total of 11 549 women were enrolled from the Maternal and Child Health Hospital of Hubei Province. Each participant accepted hrHPV testing and completed a self-administered questionnaire about basic information and potential risk factors. The univariable and multivariable logistic regression model was used to explore the associations between variants and hrHPV infection. Our results showed that hrHPV prevalence was 16.09% in Hubei Province, among which, hrHPV was more likely to be positive in women aged 51 years or above (OR=1.65, 95% CI: 1.28-2.14), and in women who had symptoms of bleeding after intercourse (OR=1.32, 95% CI:1.17-1.50), had first sexual intercourse at the age of 18 years or below (OR=1.33, 95% CI:1.07-1.64), had at least three male sexual partners (OR=2.50, 95% CI:2.07-3.03), and who had been diagnosed with sexually transmitted infections (OR=1.50, 95% CI:1.12-2.03). Married women (OR=0.66, 95% CI: 0.55-0.78) and women who frequently used condoms (OR=0.75, 95% CI:0.67-0.84) had a relatively lower hrHPV prevalence. This study confirms that hrHPV infection was associated with age, marital status, symptoms of intercourse bleeding, history of sexually transmitted infections, and sex-related behaviors. Above all, this study provides a baseline database prior to obtaining vaccinations for dynamic tracking of the changes in hrHPV prevalence.

Clinicopathological and prognostic significance of blood microvessel density in endometrial cancer: a meta-analysis and subgroup analysis.

OBJECTIVE: The study aimed to systematically review the association between angiogenesis and clinicopathological characteristics and its prognostic value in patients with endometrial cancer. METHODS: Eligible studies were searched in PubMed, Embase, China National Knowledge Infrastructure, and Wanfang database. Studies that assessed blood microvessel density (BMVD) and correlated with clinicopathological features and/or overall survival (OS) were included. Geometric mean values and hazard ratio with 95% confidence interval were pooled to examine the risk or hazard association. Subgroup analyses were conducted based on populations, BMVD criteria, BMVD markers, and type of survival analysis. RESULTS: A total of 29 studies of 2517 patients were included. BMVD was associated with depth of myometrial invasion (MI) [standard mean difference (SMD) 1.24; 95% CI 0.53-1.95; P = 0.0006], lymphovascular space invasion (LVSI) (SMD 0.75; 95% CI 0.3-1.21; P = 0.001), and lymph node metastasis (LNM) (SMD 0.99; 95% CI 0.46-1.52; P = 0.0003). BMVD was also significantly associated with poor OS (HR 2.65; 95% CI 1.86-3.77; P < 0.00001). The association remained significant in the subgroups Asian population, BMVD criteria using Weidner method, BMVD marker CD34 for MI, LVSI, and LNM, CD105 for MI, and factor VIII for MI and LNM, respectively. For OS, either Asian or non-Asian population, BMVD criteria using Weidner or non-Weidner method, BMVD marker CD31, or factor VIII antibody and analysis using univariate or multivariate were all significantly associated. CONCLUSIONS: BMVD was associated with deeper MI, positive LVSI, positive LNM, and poor OS in patients with endometrial cancer. Therefore, angiogenesis is a useful measure for poor clinicopathological outcomes and prognosis in patients with endometrial cancer.

Blastocoele expansion degree predicts live birth after single blastocyst transfer for fresh and vitrified/warmed single blastocyst transfer cycles.

OBJECTIVE: To evaluate the independent effects of the degree of blastocoele expansion and re-expansion and the inner cell mass (ICM) and trophectoderm (TE) grades on predicting live birth after fresh and vitrified/warmed single blastocyst transfer. DESIGN: Retrospective study. SETTING: Reproductive medical center. PATIENT(S): Women undergoing 844 fresh and 370 vitrified/warmed single blastocyst transfer cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live-birth rate correlated with blastocyst morphology parameters by logistic regression analysis and Spearman correlations analysis. RESULT(S): The degree of blastocoele expansion and re-expansion was the only blastocyst morphology parameter that exhibited a significant ability to predict live birth in both fresh and vitrified/warmed single blastocyst transfer cycles respectively by multivariate logistic regression and Spearman correlations analysis. Although the ICM grade was significantly related to live birth in fresh cycles according to the univariate model, its effect was not maintained in the multivariate logistic analysis. In vitrified/warmed cycles, neither ICM nor TE grade was correlated with live birth by logistic regression analysis. CONCLUSION(S): This study is the first to confirm that the degree of blastocoele expansion and re-expansion is a better predictor of live birth after both fresh and vitrified/warmed single blastocyst transfer cycles than ICM or TE grade.

Progesterone elevation on the day of human chorionic gonadotropin administration adversely affects the outcome of IVF with transferred embryos at different developmental stages.

BACKGROUND: The effect of progesterone elevation (PE) on the day of human chorionic gonadotropin (hCG) administration on the pregnancy outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles is a matter of ongoing debate. The replacement of cleavage-stage embryos with blastocyst-stage embryos for transfer was proposed to avoid the possible impairment of PE in fresh cycles. This study aimed to assess the association between PE on the day of human chorionic gonadotropin (hCG) administration and clinical pregnancy rates (CPRs) in IVF/ICSI cycles with embryos transferred at different developmental stages (cleavage and blastocyst). Moreover, a secondary aim was to determine the thresholds at which PE has a detrimental effect on CPRs. METHODS: This single-center retrospective cohort study included more than 10,000 patients undergoing day 3 cleavage-stage embryo transfer (ET) and 1146 patients undergoing day 5 blastocyst-stage embryo transfer (ET) using gonadotropin and GnRH agonist for controlled ovarian stimulation. RESULTS: Serum PE was inversely associated with CPRs in both cleavage- and blastocyst-stage ET cycles. In the day 3 ET cycles, CPRs (progesterone levels < 0.5 ng/ml, 49.2 %) significantly declined when the progesterone concentration reached 1.0 ng/ml (45.5 %) and decreased further when the progesterone concentration increased to 1.5 ng/ml (36.2 %). In the day 5 blastocyst-stage ET cycles, patients with serum progesterone levels ≥1.75 ng/ml had significantly lower CPRs (31.3 % VS. 41.4 %, p < 0.001) compared to patients with serum progesterone levels <1.75 ng/ml. The negative association of PE with CPRs was noted in both ET groups, even after adjusting for confounders. Furthermore, the developmental stage of the transferred embryos was not linked to the effect of PE on CPRs because the interaction between the developmental stage of the transferred embryos and PE was not significant. CONCLUSIONS: PE on the day of hCG administration is associated with decreased CPRs in GnRH agonist IVF/intracytoplasmic sperm injection (ICSI) cycles regardless of the developmental stage of the transferred embryos (cleavage versus blastocyst stage).