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Among all malignant tumors that threaten human health, virus-related tumors account for a large proportion. The treatment of these tumors is still an urgent problem to be resolved. The immune system is the “guard” of the human body, resisting the invasion of foreign substances such as viruses. Studies have shown that immunotherapy has clinical significance in the treatment of a variety of tumors. In particular, the emergence of immune checkpoint inhibitors (ICIs) in recent years has opened a new door to cancer therapy. Considering the potential role of ICIs in the treatment of virus-related cancers, we focused on their therapeutic effect in virus-associated cancers and explored whether the therapeutic effect in virus-associated cancers was related to virus infection status. Although there is no clear statistical significance indicates that ICIs are more effective in virus-associated cancers than non-virus infections, the efficacy of checkpoint inhibitors in the treatment of virus-related cancers is promising. We believe that this research provides a good direction for the implementation of individualized precision medicine.

As molecular analyses based on high-throughput sequencing have developed, the molecular classification of cancer has facilitated clinical work. The aim of the present study was to identify a new potential therapeutic target for cervical carcinoma by molecular analyses. We firstly tested the LOXL2 expression pattern in 50 paired normal cervix and cervical carcinoma via qPCR and immunohistochemistry, and the LOXL2 expression pattern was found to be in accordance with public datasets from Gene Expression Omnibus (GEO). Then, we comprehensively rewired the 176 cervical carcinoma samples from The Cancer Genome Atlas (TCGA), subsequently clustered the samples into two groups corresponding to LOXL2 expression to determined the associations between LOXL2 expression status and molecular characterizations of cervical carcinoma. In vitro assays for further verifying the correlations in SiHa-shLOXL2 and HeLa-shLOXL2 cell lines. In this study, we found that LOXL2 highly expressed in carcinoma tissue, with 14 CpG islands of LOXL2 promoter that were significantly and negatively associated with its expression in cervical carcinoma. And there were notable correlations among LOXL2 expression status and molecular characterizations of cervical carcinoma, including diagnostic age, HPV A7 types, mRNA molecular clusters, miRNA molecular clusters, and DNA methylation molecular clusters et al. In addition, high LOXL2 expression was negatively correlated with lower tumor mutation density, especially in EP300, ERBB2, EGFR and NOTCH2, and was negatively correlated with lower expression of APOBEC3 family genes, such as APOBEC3A, APOBEC3B, APOBEC3D, and APOBEC3G. Furthermore, high LOXL2 expression was associated with poor overall (OS) and poor disease-free survival (DFS) in cervical carcinoma, and was associated with higher epithelial-mesenchymal transition (EMT) score, enrichment of extracellular matrix (ECM) signaling, the phenotype that was found to be associated with poor prognosis Cao et al. LOXL2 With EMT in Cervical Carcinoma in cervical carcinoma from TCGA. Conversely, the ability of cell proliferation and cell migration were reversed in LOXL2 knock-down cervical cell lines via regulating the genes' expression of EMT phenotype in vitro. Overall, we demonstrated the correlation between LOXL2 expression status and cancer molecular characterizations of cervical carcinoma, and identified LOXL2 may serve as a therapeutic target for such carcinoma.

Objective: The purpose of this retrospective study was to investigate the role of 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET/CT) and evaluate if combined elevated serum tumor markers levels improve the accuracy of 18F-FDG PET/CT in detecting recurrence of cervical squamous cell carcinoma.Methods: A total number of 42 patients who were treated for cervical squamous cell carcinoma and had underwent 18F-FDG PET/CT for suspected recurrence of cervical cancer were retrospectively reviewed in this study and their clinical, pathological and serological data were collected and analyzed. The clinical value of combining 18F-FDG PET/CT with serum tumor markers was investigated.Results: Among the 42 patients, 18F-FDG PET/CT was true positive in 25 (59.5%), false positive in 5 (11.9%), true negative in 12 (28.5%) and false negative in none. The overall patient-based sensitivity, specificity, accuracy, positive predictive value and negative predictive value of 18F-FDG PET/CT in detecting recurrent cervical cancer were 100%, 70.6, 88.1%, 83.3%, and 100%, respectively. The accuracy of 18F-FDG PET/CT with combined squamous cell carcinoma antigen (SCC Ag) and carcinoembryonic antigen (CEA) elevation was 100% compared to only SCC Ag elevation and only CEA elevation, 90% and 33.3%, respectively. The positive predictive value of a positive 18F-FDG PET/CT with combined SCC Ag and CEA elevation was 100% for detection of recurrent cervical cancer. Also, the negative predictive value of a negative 18F-FDG PET/CT combined with normal SCC Ag and CEA levels was 100%.Conclusion: 18F-FDG PET/CT is highly sensitive in the diagnosis of recurrent cervical cancer. When 18F-FDG PET/CT is associated with both SCC Ag and CEA elevation or only SCC Ag elevation, the accuracy is increased but not when associated with only CEA elevation. Positive 18F-FDG PET/CT associated with both tumor markers elevation can precisely predict recurrence. Moreover, normal levels of both tumor markers with a negative 18F-FDG PET/CT result may clinically reassure that a recurrence is absent.

Cervical cancer is the second leading cause of death in female genital malignancies. Persistent infection with high-risk HPV is closely related to cervical intraepithelial neoplasia (CIN). Wide-scale HPV screening has already been implemented in developed countries. However, with advances in HPV testing methods, there are presently no better methods for the management of the increasing number of high-risk HPV-positive women except for periodic review. In order to improve screening coverage and achieve better triage of those women, we present current HPV testing methods with self-collected cervical samples, focusing on recent advances in next-generation sequencing (NGS) technologies as a promising screening technology for cervical cancer precursors.

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Human papillomavirus (HPV) integration and high expression of HPV oncogenes (E6 and E7) are important mechanisms for HPV carcinogenesis in cervical cancer. However, the relationship between HPV integration and HPV E6 spliced transcripts, as well as the underlying mechanisms of HPV integration in carcinogenesis after HPV E6 splicing remains unclear. We analyzed HPV‐coiled‐coil domain containing 106 (CCDC106) integration samples to characterize the roles of HPV integration, E6 spliceosome I (E6*I), and high CCDC106 expression in cervical carcinogenesis. We found that E6 was alternatively spliced into the E6*I transcript in HPV‐CCDC016 integration samples with low p53 expression, in contrast to the role of E6*I in preventing p53 degradation in cervical cancer cells. In addition, CCDC106 was highly expressed after HPV‐CCDC106 integration, and interacted with p53, resulting in p53 degradation and cervical cancer cell progression in vitro and in vivo. Importantly, when E6*I was highly expressed in cervical cancer cells, overexpression of CCDC106 independently degraded p53 and promoted cervical cancer cell progression. In this study, we explored the underlying mechanisms of HPV‐CCDC106 integration in HPV carcinogenesis after HPV E6 splicing, which should provide insight into host genome dysregulation in cervical carcinogenesis.