Squamous cell carcinoma antigen combined with HPV-16 infection in predicting high-grade squamous intraepithelial lesions of the cervix.

An early screening of HPV and the Thinprep Cytology Test (TCT) can effectively prevent cervical cancer. However, patients with high-grade cervical intraepithelial neoplasia usually escape current screening methods and commonly develop cervical cancer. Hence, to identify effective and specific screening methods for high-grade cervical intraepithelial neoplasia is of vital necessity. In this study, 541 patients collected in Sun Yat-Sen hospital from January 2007 to December 2016 were selected. HPV genotype detection and SCC-ag detection were done in these patients. It was found that when serum SCC-ag level exceeded over 0.39 ng/ml in HPV-16 positive patients, the sensitivity and specificity of this novel approach to predict high-grade cervical intraepithelial neoplasia could reach to 83.1% and 62.1%, respectively. The result suggested that the combination of serum SCC-ag level and HPV-16 infection could be used as a novel approach for high-grade cervical intraepithelial neoplasia screening.Impact statementWhat is already known on this subject? Patients with a high-grade cervical intraepithelial neoplasia usually escape current screening methods.What do the results of this study add? When serum SCC-ag level exceeded over 0.39 ng/ml in HPV-16 positive patients, the sensitivity and specificity to predict high-grade cervical intraepithelial neoplasia could reach to 83.1 and 62.1%, respectively.What are the implications of these findings for clinical practice and/or further research? Combination of serum SCC-ag level and HPV-16 infection could be used to screen high-grade cervical intraepithelial neoplasia.

HPV-specific risk assessment of cervical cytological abnormalities.

BACKGROUND: Cytology and HPV genotype screening play an important role in cervical cancer detection. Whether multiple HPV genotyping can predict cytological lesions remains to be further studied. METHODS: Two thousand two hundred twenty-four females were analyzed for cytology and HPV genotypes test. The possibility of predicting cytological lesions by HPV genotypes test was evaluated by multivariate logistic regression and area under the receiver operator characteristic curve (AUC). RESULT: Abnormal cytological results were found in 479 participants. A total of 688 patients were detected with HPV infection, 619 with HR-HPV infection and 112 with LR-HRV infection. HPV-52 was found to be the most common type among these patients, and a relatively higher risk of cervical lesions was found in HPV positive females. HPV-16, 31, 33 and 58 were found to have significantly higher infection rates in patients with HSIL and higher lesions. The prediction model was developed based on age and HPV-specific genotypes, with the AUC of 0.73 for cytological abnormalities and 0.82 for HSIL and higher lesions. CONCLUSION: HPV-16, 31, 33 and 58 infection are significant risk factors for cervical lesions. Combined HPV genotypes test can effectively predict cytological abnormalities.

Pembrolizumab in FIGO IVB Verrucous Carcinoma of the Vulva: A Case Report.

BACKGROUND: Vulvar cancer is the fourth most common gynecologic cancer, and prognosis is poor in advanced vulvar cancer patients. Treatment for advanced vulvar cancer has not been satisfactory. In this report, we firstly report a FIGO IVB vulva verrucous carcinoma patient who obtained good prognosis after systemic treatment. CASE PRESENTATION: A patient was admitted to hospital due to her vulvar lesion persistent for past 14 years. The vulvar mass has widely invaded urethra, part of anus, the lower third of the vagina, bilateral superior and inferior branches of pubis, and bilateral internal and external muscles of obturator. Multiple metastatic lymph nodes were also found in the pelvic cavity. The histopathological studies confirmed vulvar verrucous carcinoma with a PD-L1 overexpression. After six courses of neoadjuvant chemotherapy and pembrolizumab, the patient underwent radical vulvectomy and achieved optimal cytoreduction. Postoperative pathology found no residual tumor. The patient then received one course of postoperative chemotherapy and pembrolizumab, underwent radiation therapy, and was disease free after 6 months follow-up. CONCLUSION: Our individualized treatment strategy is successful. Pembrolizumab is safe and effective in the treatment of advanced vulvar verrucous carcinoma with PD-L1 overexpression.

Long non-coding RNA AK001903 regulates tumor progression in cervical cancer.

A majority of cervical cancers are squamous cell carcinomas, arising from the squamous (flattened) epithelial cells that line the cervix. Long noncoding RNAs (lncRNAs) are a unique class of messenger RNA-like transcripts of at least 200 nucleotides in length with no significant protein-coding capacity. Aberrant lncRNA expression is emerging as a major component of the cancer transcriptome. In the present study, lncRNA microarrays were conducted to investigate the differentially expression lncRNAs in cervical cancer (CC) tissues compared with peritumoral tissues. Then, the most significantly upregulated lncRNA, which was lncRNA-AK001903 was selected to conduct further experiments. Real-time Quantitative polymerase chain reaction was conducted to investigate lncRNA-AK001903 expression in CC tissues and Hela, Siha, Ca Ski, C33a, H8 (HPV-immortalized cervical epithelial cell line) cell lines, and in situ hybridization histochemistry (ISHH) was performed to detect lncRNA-AK001903 expression level in different CC stages. The effect of lncRNA-AK001903 on cell proliferation, invasion and migration was assessed after knockdown of lncRNA-AK001903. The findings of the study confirmed that lncRNA-AK001903 was upregulated in CC cells and tissues compared with normal cell line H8 and peritumoral tissues. ISHH demonstrated that the expression level of lncRNA-AK001903 was connected with International Federation of Gynecology and Obstetrics (2018) stage of CC. Knockdown of lncRNA-AK001903 inhibited cell proliferation, invasion and migration in Ca Ski cells. In conclusion, lncRNA-AK001903 was demonstrated to be an oncogenic lncRNA that promotes tumor progression and may be an effective target for CC treatment in the near future.

ALDH-1-positive cells exhibited a radioresistant phenotype that was enhanced with hypoxia in cervical cancer.

BACKGROUND: We have previously found there was a small subpopulation of cells with cancer stem cell-like phenotype ALDH-1 in cervical cancer. Radiotherapy has been applied in most of the cervical cancer. However,the mechanisms underlying radioresistance still remained elusive. Our study is to explore whether ALDH+ cell promotes radioresistance by hypoxia. METHODS: Cells were respectively cultured in hypoxia and normoxia environment and analyzed for marker stability, and cell cycle distribution. RESULTS: Cell growth, apoptosis, cell cycle, sphere formation were affected by hypoxia. ALDH-1 and CHK2 were upregulated after hypoxia. CONCLUSIONS: Here we show that ALDH-1 positive cells contribute to cervical carcinoma radioresistance through preferential activation of the DNA damage checkpoint response and an increase in DNA repair capacity. The fraction of these cells is enriched after radiation in cervical carcinoma.

Low GAS5 expression may predict poor survival and cisplatin resistance in cervical cancer.

Cisplatin resistance is a major challenge in cervical cancer (CC) chemotherapy. Growth arrest-specific 5 (GAS5) has been reported to be a tumour suppressor gene in CC. However, the mechanism of GAS5 in chemoresistance remains undetermined. Our research evaluated GAS5 expression in normal and CC tissues by qPCR and in situ hybridization (ISH). Statistical analysis was conducted to analyse the association of GAS5 expression with survival. Biochemical methods were used to screen upstream and downstream regulators of GAS5. Then, interactions were confirmed by ChIP, RNA pull-down, RNA immunoprecipitation (RIP), dual-luciferase reporter and real-time PCR assays. The cisplatin sensitivity of GAS5-overexpressing CC cells was demonstrated in vitro and in vivo. The results showed that low GAS5 expression was correlated with poor overall survival. Mechanistically, GAS5 was transcriptionally modulated by P-STAT3 and served as a competing endogenous RNA (ceRNA) of miR-21 to indirectly affect cisplatin sensitivity through PDCD4 regulation in CC cells. Animal studies confirmed that GAS5 enhanced cisplatin sensitivity and promoted PDCD4 expression in vivo. GAS5 was regulated by P-STAT3 and affected the sensitivity of CC to cisplatin-based chemotherapy through the miR-21/PDCD4 axis. This result may provide new insight into cisplatin-based therapy.

Growth arrest-specific 5 attenuates cisplatin-induced apoptosis in cervical cancer by regulating STAT3 signaling via miR-21.

Cervical cancer is the most common cause of female cancer-related mortality worldwide. Decreased expression of long noncoding RNA growth arrest-specific 5 (GAS5) is found in human cervical cancer tissues and associated with poor prognosis. However, the studies on associations between GAS5 level and malignant phenotypes, as well as sensitivity to chemotherapeutic drug in cervical cancer cells are limited. In this study, overexpression of GAS5 in cervical cancer cells resulted in prohibited cell proliferation and colony formation, which were promoted by siGAS5. Enhanced GAS5 increased cell percentage in the G0/G1 phase and decreased cells percentage in the S phase, whereas reduced expression did not. The malignant behaviors of cervical cancer cells, manifested by cell migration and invasion, could be weakened by the GAS5 overexpression and enhanced by siGAS5. Furthermore, in cisplatin-induced cell, overexpression of GAS5 reduced cells viability and enhanced apoptosis, whereas in cells transfected with siGAS5, apoptosis eliminated. We have reported the upregulation of microRNA-21 (miR-21) and its oncogenetic roles in cervical cancer previously. In this study, we found the negative relationship between the GAS5 and miR-21. Moreover, the decrease of miR-21 associated proteins phosphorylated STAT3 and E2F3 was seen in GAS5 overexpressed cells, both of which could be increased by siGAS5. The GAS5 deficiency also reduced miR-21 target proteins TIMP3 and PDCD4 expressions. Taken together, the GAS5 expression level is inversely associated with malignancy, but positively associated with sensitivity to cisplatin-induced apoptosis, suggesting that GAS5 could be a biomarker of cisplatin-resistance in clinical therapy of human cervical cancer.

Diagnostic Value of Assessment of Cervical Involvement in Early-Stage Endometrial Adenocarcinoma: Comparison of Magnetic Resonance Imaging (MRI) Versus Hysteroscopy.

BACKGROUND The aim of this study was to compare magnetic resonance imaging (MRI) and hysteroscopy (HS) for assessing cervical involvement in early-stage endometrial adenocarcinoma in order to establish a more reliable screening method to aid in clinical decision-making. MATERIAL AND METHODS A retrospective analysis was performed on the clinicopathological data from 88 patients with stage I or II endometrial adenocarcinoma who underwent MRI and HS prior to surgery in the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China. Chi-square and Fisher's exact tests were performed to compare the accuracy, sensitivity, specificity, and positive and negative predictive values in the diagnosis of cervical involvement by MRI and HS. The relationship between clinicopathological factors and the deviation of diagnosis by MRI and HS from that by pathology was also analyzed. RESULTS The accuracy of assessing cervical conditions was 93.2% by MRI and 55.7% by HS. Among these variables, the accuracy, specificity, and positive predictive values of MRI were significantly different from those of HS, while the sensitivity and negative predictive values of MRI and HS were not significantly different from each other. Age, tumor size, tumor differentiation, and depth of myometrial invasion were not associated with the differences in cervical assessment between MRI and HS. However, the tumor location may affect assessment by HS. CONCLUSIONS MRI is better than HS for cervical assessment. The negative predictive values of both MRI and HS are high and unsatisfactory.

Cervical cancer stem cells.

The concept of cancer stem cells (CSC) has been established over the past decade or so, and their role in carcinogenic processes has been confirmed. In this review, we focus on cervical CSCs, including (1) their purported origin, (2) markers used for cervical CSC identification, (3) alterations to signalling pathways in cervical cancer and (4) the cancer stem cell niche. Although cervical CSCs have not yet been definitively identified and characterized, future studies pursuing them as therapeutic targets may provide novel insights for treatment of cervical cancer.

Expression and functional role of ALDH1 in cervical carcinoma cells.

Tumor formation and growth is dictated by a very small number of tumor cells, called cancer stem cells, which are capable of self-renewal. The genesis of cancer stem cells and their resistance to conventional chemotherapy and radiotherapy via mechanisms such as multidrug resistance, quiescence, enhanced DNA repair abilities and anti-apoptotic mechanisms, make it imperative to develop methods to identify and use these cells as diagnostic or therapeutic targets. Aldehyde dehydrogenase 1 (ALDH1) is used as a cancer stem cell marker. In this study, we evaluated ALDH1 expression in CaSki, HeLa and SiHa cervical cancer cells using the Aldefluor method to isolate ALDH1-positive cells. We showed that higher ALDH1 expression correlated with significantly higher rates of cell proliferation, microsphere formation and migration. We also could demonstrate that SiHa-ALDH1- positive cells were significantly more tumorigenic compared to SiHa-ALDH1-negative cells. Similarly, SiHa cells overexpressing ALDH1 were significantly more tumorigenic and showed higher rates of cell proliferation and migration compared to SiHa cells where ALDH1 expression was knocked down using a lentivirus vector. Our data suggested that ALDH1 is a marker of cervical cancer stem cells and expand our understanding of its functional role.