Human papillomaviruses (HPV) are the first viruses to have been acknowledged to prompt carcinogenesis, and they are linked with cancers of the uterine cervix, anogenital tumors, and head and neck malignancies. This paper examines the structure and primary genomic attributes of HPV and highlights the clinical participation of the primary HPV serotypes, focusing on the roles that HPV-16 and 18 play in carcinogenesis. The mechanisms that take place in the progression of cervical neoplasia are described. The oncogenic proteins E6 and E7 disrupt control of the cell cycle by their communication with p53 and retinoblastoma protein. Epidemiological factors, diagnostic tools, and management of the disease are examined in this manuscript, as are the vaccines currently marketed to protect against viral infection. We offer insights into ongoing research on the roles that oxidative stress and microRNAs play in cervical carcinogenesis since such studies may lead to novel methods of diagnosis and treatment. Several of these topics are surfacing as being critical for future study. One particular area of importance is the study of the mechanisms involved in the modulation of infection and cancer development at cervical sites. HPV-induced cancers may be vulnerable to immune therapy, offering the chance to treat advanced cervical disease. We propose that oxidative stress, mRNA, and the mechanisms of HPV infection will be critical points for HPV cancer research over the next decade.

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Cervical cancer is the second most common type of cancer among women worldwide and a leading cause of mortality in women. Metastases reduce the overall survival rate in patients with cervical cancer. Thus, it is clinically urgent to investigate the molecular mechanism of cervical cancer metastasis. The aim of the present study was to investigate the mechanism of microRNA (miR)-378 in the metastasis of cervical cancer. In the present study, miR-378 expression levels were significantly upregulated in cervical cancer tissues and cervical intraepithelial neoplasia III tissues when compared with normal cervix tissues. Re-expression of miR-378 significantly promoted tumor migration and invasion in vitro, and metastasis in vivo, while downregulation of miR-378 suppressed the effect in vitro. Luciferase reporter assay revealed that autophagy-related protein 12 (ATG12) was a direct target of miR-378 and its expression was downregulated by miR-378. In cervical cancer tissues with lymph node metastasis, miR-378 was upregulated while ATG12 was downregulated when compared with lymph node negative cases. To the best of our knowledge, the present study is the first to provide evidence that miR-378 may be associated with ATG12. Collectively, the data of the present study suggested that miR-378 may function as an oncogene by promoting metastasis in cervical cancer. The finding that miR-378 targets ATG12 indicated that miR-378 may have a potential role in autophagy. These findings may provide novel insights into the mechanism of metastasis in cervical cancer and a novel therapeutic target for the treatment of cervical cancer.

Cancer cells undergo metabolic changes that support their malignant growth. These changes are often associated with increased expression of the rate-limiting glycolytic enzyme hexokinase 2. Hexokinase 2 is an enzyme that catalyzes the conversion of glucose to glucose-6-phosphate. In this study, we utilized Gene Expression Profiling Interactive Analysis (GEPIA) database analysis and clinical sample analysis to find that hexokinase 2 was highly expressed in cervical cancer. Furthermore, we found that high hexokinase 2 expression in cervical cancer demonstrated a positive correlation with tumor size ( P = .009696), pathological grade ( P = .028551), and prognosis ( P = .00069) but not with age ( P = .956201) or lymph node metastasis ( P = .131379). At the cellular level, we knocked down the expression of hexokinase 2 in the human cervical cancer cell line SiHa. The results demonstrated that knockdown of hexokinase 2 inhibited the proliferation and migration of SiHa cells and promoted cell apoptosis. During this process, knockdown of hexokinase 2 inhibited phosphorylation of AKT and mammalian target of rapamycin and promoted p53 expression. At the same time, overexpression of human papillomavirus 18 oncogenes E6 and E7 significantly promoted the expression of hexokinase 2. Most importantly, we discovered a novel upstream regulatory microRNA for hexokinase 2: miR-9-5p. Luciferase reporter assays and Western blot assays demonstrated that hexokinase 2 expression was inhibited by miR-9-5p by directly binding its 3′-untranslated region in SiHa cells. Next, we determined that miR-9-5p could suppress the proliferation and migration of SiHa cells and induce apoptosis. In conclusion, we found that hexokinase 2 serves a carcinogenic role in cervical cancer through the miR-9-5p/hexokinase 2/AKT pathway, which serves as the basis for potential therapeutic targets and prognostic indicators.

Taking the emergence of continuous resistance to chemotherapy and the evidence that miRNAs are associated with chemoresistance in cancers into consideration, it is of significant importance to reveal the miRNAs functions for the treatment of cancer. As a novel tumor suppressor, MiR-634 is known to induce apoptosis in tumor cell which is essential for tumorigenesis. Herein, we elucidated the regulation effects of miR-634 in gene expression and discovery of its target gene in cell proliferation and invasion that would aid therapeutic apoptosis. As a result, by targeting mTOR signal pathway, miR-634 inhibited cell proliferation, migration and invasiveness in cervical cancer cells and the block of miR-634 enhances the mTOR expression at both the mRNA and protein levels which regulated the expression of mTOR negatively. Taken together, these results further indicated that miR-634 is an effective target for cancer treatment, and the findings provided in this work might lead to the better understanding of the malignant behavior of cervical carcinoma.

ObjectiveTo determine the clinicopathologic and immunohistochemical predictors of the persistence/recurrence of cervical intraepithelial neoplasia (CIN) after cervical conization.MethodsMedical records of 502 patients who received cervical conization treatment of CIN between 2005 and 2012 were reviewed. The clinicopathologic parameters were analyzed using Cox hazard regression. Fifty patients with CIN persistence/recurrence were matched to 50 cases without CIN persistence/recurrence. These 100 cervical specimens were assessed for expression of insulin-like growth factor II messenger RNA (mRNA)-binding protein 3 (IMP3), targeting protein for xenopus kinesin-like protein 2 (TPX2), and programmed cell death-1 ligand-1 (PD-L1) using immunohistochemical staining.ResultsMultivariate analysis found that the independent predictors of CIN persistence/recurrence were positive surgical margin (hazard ratio 5.777, 95% confidence interval 2.334–14.301, p < 0.001) and human papilloma virus persistence for 6 months (hazard ratio 20.685, 95% confidence interval 7.350–57.657, p < 0.001). Co-expression of TPX2 and PD-L1 was significantly higher in CIN persistence/recurrence group than the group without CIN persistence/recurrence (p = 0.013). The depth of glandular involvement (GI) was less than 3mm in about 86.8% (59/68) CIN2-3 lesions, However, No statistically significant associations between GI and persistence/recurrence were observed (P = 0.58).ConclusionPositive surgical margin, HPV persistence, and expression of both TPX2 and PD-L1 are associated with persistence/recurrence of cervical intraepithelial neoplasia after cervical conization.

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B7-H3, a co-stimulatory molecule, has been found expressed in ovarian cancer, but its role and mechanism is not clear. In this study, we further verified the expression of B7-H3 in ovarian carcinoma and normal epithelial ovarian tissues. Three ovarian cancer cell lines, A2780, SKOV3 and HO8910 were selected to explore the effects of B7-H3 on proliferation, apoptosis, migration and invasion. We found that B7-H3 was mainly located in the cytoplasm of ovarian cancer cells as determined by immunofluorescence staining. The ability of cell invasion, migration, proliferation decreased after silencing B7-H3 whereas the apoptosis increased, which was related to the upregulation of Bax, caspase-8, cleaved caspase-8 and the downregulation of Bcl-2, Bcl-xl, matrix metalloproteinase-2 (MMP2) by western blotting. In addition, B7-H3 enhanced the H08910 cell capacities in invasion, migration and proliferation. Expression of the phosphorylation signal transducer and activator of transcription 3 (pStat3) molecules and their upstream molecules phosphorylation Janus kinase 2 (pJak2) were significantly increased. In order to investigate whether B7-H3 plays a role in this pathway, we treated the overexpressed HO8910 cells with AG490 (inhibitors of Jak2). Our findings revealed that B7-H3 affect ovarian cancer progression through the Jak2/Stat3 pathway, indicating that B7-H3 has the potential to be a useful prognostic marker.