Methylation of p16 is an important mechanism in cervical carcinogenesis. However, the relationship between cervical squamous cell carcinoma (SCC) and Epstein-Barr virus (EBV) remains controversial. Here, we explored whether EBV infection and/or p16 gene inactivation would play any role in cervical carcinogenesis. Eighty-two specimens included 41 invasive SCCs, 30 cervical intraepithelial neoplasm (CIN; CIN 1, 11 cases, CIN II, 3 cases, CIN III 16 cases) and 11 nonneoplastic cervices. EBV was detected by polymerase chain reaction (PCR) for EBNA-1 and in situ hybridization for EBER-1. The p16 methylation-status and the expression of p16 protein were studied by methylation-specific PCR and immunohistochemistry, respectively. The materials were divided into four groups: 1) nonneoplastic cervices, 2) CIN I, 3) CIN II-III and 4) invasive SCCs. p16 methylation and p16 immunoexpressions increased in CIN and invasive SCCs than nonneoplastic tissue. p16-methylation and p16-immunoreactivities were higher in the EBV-positive group (p=0.009, p<0.001) than in the EBV-negative group. EBV was detected more frequently in CIN and SCCs than nonneoplastic cervices. In conclusion, a correlation between p16 methylation, p16 immunoreactivity and the detection of EBV strongly suggested that the cooperation of EBV and p16 gene may play a synergic effect on cell cycle deregulation.

The burden of HPV-associated premalignant and malignant cervical lesions remains high in HIV+ women even under ART treatment. In order to identify possible underlying pathophysiologic mechanisms, we studied activation and HIV co-receptor expression in cervical T-cell populations in relation to HIV, HPV and cervical lesion status.

Cervical cancer (CC), a leading cause of cancer-related deaths in women worldwide, has been causally linked to genital human papillomavirus (HPV) infection. Although a host of genetic alterations have been identified, molecular basis of CC development is still poorly understood.

Background: This study constructed and demonstrated a model to predict the overall survival (OS) of newly diagnosed distant metastatic cervical cancer (mCC) patients. Methods: The SEER (Surveillance, Epidemiology, and End Results) database was used to collect the eligible data, which from 2010 to 2016. Then these data were separated into training and validation cohorts (7:3) randomly. Cox regression analyses was used to identify parameters significantly correlated with OS. Harrell's Concordance index (C-index), calibration curves, and decision curve analysis (DCA) were further applied to verify the performance of this model. Results: A total of 2,091 eligible patients were enrolled and randomly split into training (n = 1,467) and validation (n = 624) cohorts. Multivariate analyses revealed that age, histology, T stage, tumor size, metastatic sites, local surgery, chemotherapy, and radiotherapy were independent prognostic parameters and were then used to build a nomogram for predicting 1 and 2-year OS. The C-index of training group and validation group was 0.714 and 0.707, respectively. The calibration curve demonstrated that the actual observation was in good agreement with the predicted results concluded by the nomogram model. Its clinical usefulness was further revealed by the DCAs. Based on the scores from the nomogram, a corresponding risk classification system was constructed. In the overall population, the median OS time was 23.0 months (95% confidence interval [CI], 20.5-25.5), 12.0 months (95% CI, 11.1-12.9), and 5.0 months (95% CI, 4.4-5.6), in the low-risk group, intermediate-risk group, and high-risk group, respectively. Conclusion: A novel nomogram and a risk classification system were established in this study, which purposed to predict the OS time with mCC patients. These tools could be applied to prognostic analysis and should be validated in future studies.

Non-invasive physical plasma (NIPP) generated by non-thermally operated electrosurgical argon plasma sources is a promising treatment for local chronic inflammatory, precancerous and cancerous diseases. NIPP-enabling plasma sources are highly available and medically approved. The purpose of this study is the investigation of the effects of non-thermal NIPP on cancer cell proliferation, viability and apoptosis and the identification of the underlying biochemical and molecular modes of action. For this, cervical cancer (CC) single cells and healthy human cervical tissue were analyzed by cell counting, caspase activity assays, microscopic and flow-cytometric viability measurements and molecular tissue characterization using Raman imaging. NIPP treatment caused an immediate and persisting decrease in CC cell growth and cell viability associated with significant plasma-dependent effects on lipid structures. These effects could also be identified in primary cells from healthy cervical tissue and could be traced into the basal cell layer of superficially NIPP-treated cervical mucosa. This study shows that NIPP treatment with non-thermally operated electrosurgical argon plasma devices is a promising method for the treatment of human mucosa, inducing specific molecular changes in cells.

High-risk human papilloma virus (HR HPV) testing and liquid-based cytology are used for primary cervical screening. Digital cytology, based on whole-slide scanned samples, is a promising technique for teaching and diagnostic purposes. The aim of our study was to evaluate the interobserver and intraobserver variation in low-grade squamous lesions, HR HPV status bias, and the use of whole-slide scanned digital cervical cytology slides.

There remains uncertainty about the role of human papillomavirus (HPV) infection in causing small-cell neuroendocrine carcinoma (SCNC) and large-cell neuroendocrine carcinoma (LCNC) of the cervix. To clarify the role of HPV in the development of SCNC and LCNC, we conducted a systematic review and meta-analyses.

Objectives: To evaluate the oncological outcomes and safety of ovarian preservation, and to review the prognostic factors for ovarian metastases in early stage cervical adenocarcinoma. Methods: PubMed, Embase, and Cochrane databases were searched for publications up to January 2019. Two investigators independently screened the studies for eligibility and extracted specific data. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using STATA statistical software version 19.0. Results: A total of 68 unique manuscripts were identified through the search strategy, and 10 studies were included in the meta-analysis of the safety of ovarian preservation. Fixed-effects model was used because of moderate heterogeneity. Pooled results of the included studies showed that ovarian preservation is not associated with a statistically significant OS (OR 1.00, 95% CI 0.64-1.56, I 2 = 25.7%) or PFS (OR 0.98, 95% CI 0.57-1.66, I 2 = 0%) in early stage cervical adenocarcinoma. In addition, 19 studies were included in the review of prognostic factors for cervical adenocarcinoma and risk factors for ovarian metastases. The incidence of ovarian metastases was 0% in stage IA, 2.8% in stage IB, 3.4% in stage IIA, and 11.8% in stage IIB cervical adenocarcinoma. International Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, deep stromal invasion (DSI), lymph node metastasis (LNM), and vaginal invasion were significantly related to poor prognosis. Risk factors associated with ovarian metastases included age, FIGO stage, tumor size, DSI, parametrial invasion, corpus uteri invasion, LNM, vaginal invasion, and blood vessel invasion. Conclusions: Ovarian preservation in young patients with early stage cervical adenocarcinoma is safe and has no significant effect on OS or PFS. Preserving ovaries in patients with FIGO stage IIB seems not reasonable because of the high rate of ovarian metastasis.

Background This study aimed to investigate the association between radiotherapy for cancer and cardiovascular disease (CVD) deaths and evaluate the relative risk for CVD deaths in the general population and among patients with cancer treated with radiotherapy. Methods and Results The statistics of cancers from 16 sites were extracted from the Surveillance, Epidemiology, and End Results database and evaluated. Multivariable Cox proportional hazards regression analysis was used to analyze the association between radiotherapy and cardiovascular-specific survival. The standardized mortality ratio for CVD deaths was estimated by comparing the observed deaths of patients with cancer treated with radiotherapy to the expected deaths of the general population. Of the 2 214 944 patients identified from the database, 292 102 (13.19%) died from CVD. Multivariable Cox proportional hazards regression analyses demonstrated that radiotherapy was an independent risk factor for cardiovascular-specific survival among patients with lung and bronchus, cervix uteri, corpus uteri, and urinary bladder cancers. The long-term cardiovascular-specific survival of patients with cancer who underwent radiotherapy was significantly lower than that of patients who did not undergo radiotherapy. The incidence of CVD deaths among patients with lung and bronchus, cervix uteri, corpus uteri, and urinary bladder cancers who underwent radiotherapy was higher than that among the general population. Standardized mortality ratio significantly decreased with increasing age at cancer diagnosis, gradually decreased within 10 years of diagnosis and increased after 10 years of diagnosis. Conclusions Radiotherapy is associated with worse cardiovascular-specific survival in patients with lung and bronchus, cervix uteri, corpus uteri, and urinary bladder cancers. Long-term surveillance of cardiovascular conditions should be performed after radiotherapy.

The etiology of many human complex diseases or traits involves interactions between chemicals and genes that regulate important physiological processes. It has been well documented that chemicals can contribute to disease development through affecting gene expression in vivo In this study, we developed a flexible tool CGSEA for scanning the candidate chemicals associated with complex diseases or traits. CGSEA only need genome-wide summary level data, such as transcriptome-wide association studies (TWAS) and mRNA expression profiles. CGSEA was applied to the GWAS summaries of attention deficiency/hyperactive disorder, (ADHD), autism spectrum disorder (ASD) and cervical cancer. CGSEA identified several significant chemicals, which have been demonstrated to be involved in the development or treatment of ADHD, ASD and cervical cancer. The CGSEA program and user manual are available at https://github.com/ChengSQXJTU/CGSEA.

This present study delineates the syntheses, detailed characterization and anti-proliferative potential against SiHa (cervical cancer cell) of two mononuclear complexes of Cu(ii) and Ni(ii) using a Schiff base ligand (L) derived from 2-hydroxybenzaldehyde and N-methyl-propane 1,3-diamine. The crystallographic results show the centro-symmetric space group of orthorhombic nature (Pccn) for Cu(ii) complex (1) where the central Cu(ii) has an inversion center symmetry with six co-ordinations resulting in a distorted octahedral geometry. Whereas, in complex (2), the two independent Ni(ii) atoms present in the special position within version symmetry and form a distorted geometry of octahedral nature with six coordinations. Absorption spectral titrations with Calf Thymus (CT) DNA and the extent of the decrease in relative emission intensities of DNA-bound ethidium bromide (EB) upon adding the complexes reveal the parallel trend in DNA binding affinities for both the complexes but with a small extent of binding capabilities. Bovine serum albumin (BSA) interaction studies demonstrate that complex 1 exhibits more promiscuous binding with BSA as compared to complex 2 from the spectroscopic and theoretical approaches. α,α-Diphenyl-β-picrylhydrazyl (DPPH) free radical scavenging method shows a little antioxidant or free radical scavenging activity for both the studied complexes. Cytotoxicity studies against SiHa expressed that the percentage of cell viability was reduced with time whereas in the same concentration and conditions, the viability percentage was higher for 3T3-L1 (several normal cell lines of mouse). The fluorescence imaging obtained from acridine orange (AO) and ethidium bromide (EtBr) demonstrates that the colour of the cancer cells has changed gradually dictating the cell apoptosis from day 1 to day 3.

Contractions of the non-pregnant uterus play a key role in fertility. Yet, the electrophysiology underlying these contractions is poorly understood. In this paper, we investigate the presence of uterine electrical activity and characterize its propagation in unstimulated ex vivo human uteri. Multichannel electrohysterographic measurements were performed in five freshly resected human uteri starting immediately after hysterectomy. Using an electrode grid externally and an electrode array internally, measurements were performed up to 24 h after hysterectomy and compared with control. Up to 2 h after hysterectomy, we measured biopotentials in all included uteri. The median root mean squared (RMS) values of the external measurements ranged between 3.95 μV (interquartile range (IQR) 2.41-14.18 μV) and 39.4 μV (interquartile range (IQR) 10.84-105.64 μV) and were all significantly higher than control (median RMS of 1.69 μV, IQR 1.13-3.11 μV), consisting of chicken breast meat. The RMS values decreased significantly over time. After 24 h, the median RMS (1.27 μV, IQR 0.86-3.04 μV) was comparable with the control (1.69 μV, IQR 1.13-3.11 μV, p = 0.125). The internal measurements showed a comparable pattern over time, but overall lower amplitude. The measured biopotentials propagated over the uterine surface, following both a plane-wave as well as an erratic pattern. No clear pacemaker location nor a preferred propagation direction could be identified. These results show that ex vivo uteri can spontaneously generate propagating biopotentials and provide novel insight contributing to improving our understanding of the electrophysiology of the human non-pregnant uterus.

Circular RNA (circRNA) is a type of stable non-coding RNA that modifies macrophage inflammation by sponging micro RNAs (miRNAs), binding to RNA-binding proteins, and undergoing translation into peptides. Activated M1 phenotype macrophages secrete matrix metalloproteinases to participate in softening of the cervix uteri to promote vaginal delivery.

Tumor tissue-associated KLKs (kallikrein-related peptidases) are clinically important biomarkers that may allow prognosis of the cancer disease and/or prediction of response/failure of cancer patients to cancer-directed drugs. Regarding the female/male reproductive tract, remarkably, all of the fifteen KLKs are expressed in the normal prostate, breast, cervix uteri, and the testis, whereas the uterus/endometrium and the ovary are expressing a limited number of KLKs only.

Human papillomavirus (HPV) attributable cancer burden is currently unknown in China, which is essential to evaluate the potential benefit of existing HPV vaccines and to inform cancer control policy.

Adenocarcinomas (ACs) and squamous cell carcinomas (SCCs) differ by clinical and molecular characteristics. We evaluated the characteristics of carcinogenesis by modeling the age patterns of incidence rates of ACs and SCCs of various organs to test whether these characteristics differed between cancer subtypes.

Uterine diffuse large B-cell lymphoma (DLBCL) is a rare clinical condition. Most studies for uterine DLBCL are derived from case reports and series. Our main objective was to present a new case while also investigating the demographic, clinical characteristics, and survival of women with primary uterine DLBCL as compared to non-uterine DLBCL using the Surveillance, Epidemiology, and End Results incidence database. We queried the Surveillance, Epidemiology, and End Results database for women aged 18 years or older with a diagnosis of primary DLBCL from 1975 to 2017. The most common site of primary uterine DLBCL is the cervix uteri not otherwise specified, followed by endometrium, uterus not otherwise specified, corpus uteri, myometrium and isthmus uteri. Non-uterine DLBCL cases tend to be older than uterine DLBCL cases. Uterine DLBCL is most common among women aged 40 to 64 years. Patients with uterine DLBCL showed greater survival than non-uterine DLBCL patients, and patients treated in the rituximab era also exhibited a survival benefit. Both the elderly and African American cohorts experienced worse overall survival.

Precancerous lesions of human cervix uteri have a tendency for regression or progression. In cervical intraepithelial neoplasia grade 2 (CINII) case there is an uncertainty if a lesion will progress or regress. The carbonic anhydrase IX (CAIX) enzyme is overexpressed in cervical cancer which is more sensitive to radiotherapy. CAIX is associated with poor prognosis in solid hypoxic tumors. The aim of this study was to determine factors related to elevated soluble CAIX (s-CAIX) in high-grade intraepithelial lesion (HSIL) cases.

Breast cancer survivors are at an increased risk of second primary cancers, and the risk factors for the latter may have clinical significance. The aims of our study were to evaluate the incidences and risk factors of second primary female genital cancers (corpus uteri, cervix uteri plus ovary) in a large cohort of breast cancer survivors. Using the Surveillance, Epidemiology, and End Results (SEER) database, we examined the standardized incidence ratio (SIR) and risk factors for second primary female genital cancers observed between 2000 and 2014. Breast cancer survivors had increased SIRs for second corpus uteri cancers and second ovarian cancers and a decreased SIR for second cervical cancers (SIR 1.17, 1.12, and 0.64, respectively). Risk factors of second corpus uteri cancers were the age at first cancer diagnosis, race (black vs. white, aHR = 1.142 95% CI 1.005-1.298), and progesterone receptor (PR) status (PR+ vs. PR-, aHR = 1.131 95% CI 1.004-1.273). In addition, the risk of second ovarian cancer was positively associated with age while inversely associated with race (black vs. white, aHR = 0.691 95% CI 0.555-0.859) and estrogen receptor (ER) status (ER+ vs. ER-, aHR = 0.655 95% CI 0.544-0.788). Age, race, and hormone receptor status are risk factors of developing second female genital cancers among breast cancer survivors. Older age, black race, and a PR+ status in survivors are associated with a higher risk of second corpus uteri cancers. Additionally, older age and an ER- status should increase vigilance for potential second ovarian cancers.

Cervical cancer is a female-specific cancer with relatively high morbidity and mortality. As known to all, immune cell infiltrations in the cancer microenvironment are closely related to the cancer diagnosis and prognosis. Here we revealed that the CD8+ T cell infiltration was significantly upregulated in cervical cancer versus normal cervix uteri samples. Through univariate and multivariate cox analyses, we discovered that the CD8+ T cell infiltration was the only independent beneficial factor for the prognosis of cervical cancer. To explore the genes associated with the CD8+ T cell infiltration in cervical cancer, we performed the WGCNA analysis on the differentially expressed genes (DEGs) of cervical cancer versus normal cervix uteri tissues. As a result, 231 DEGs were found to be associated with CD8+ T cell infiltration in cervical cancer. Subsequently, with the Cytoscape analysis, we identified 105 hub genes out of the 231 DEGs. To further explore the genes that might be responsible for the prognosis of cervical cancer, we performed a univariate cox analysis followed by a LASSO assay on the 105 hub genes and located four genes (IGSF6, TLR10, FCRL3, and IFI30) finally. The four genes could be applied to the prediction of the prognosis of cervical cancer, and relatively higher expression of these four genes predicted a better prognosis. These findings contributed to our understanding of the prognostic values of CD8+ T cell infiltration and its associated genes in cervical cancer and thus might benefit future immune-related therapies.