scholarly journals A New HPV score System Predicts the Survival of Patients With Cervical Cancers

2021 ◽  
Vol 12 ◽  
Author(s):  
Qunchao Hu ◽  
Yani Wang ◽  
Yuchen Zhang ◽  
Yanjun Ge ◽  
Yihua Yin ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Treatment Strategies ◽  
Hpv Infection ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Infection Status ◽  
Cox Models ◽  
Score System ◽  
Hpv Status ◽  
The Impact

Persistent high-risk human papillomavirus (hrHPV) infection is confirmed as the major cause of cervical cancer. According to the HPV infection status, cervical cancer could be generalized as following three subgroups: HPV-negative, pure HPV-infection, and HPV-integration. Currently, the impact of HPV status on cervical cancer prognosis remains under dispute. Therefore, we explored the potential correlation between HPV status and the clinical outcome of cervical cancer, by establishing a robust prognostic predicting model based on a cervical cancer cohort using The Cancer Genome Atlas (TCGA) database. We performed an iCluster algorithm incorporating DNA copy number variation, SNP, DNA methylation, mRNA expression, and miRNA expression profile together and classified the cohort into three clusters. According to defined clusters, we established an HPV score system by weighing resultant gene alterations through random forest and COX models. This prediction tool could help to identify cervical cancer prognosis through evaluating individual HPV infection status and subsequent genetic modification, which might provide insights into HPV-related gene driven cervical cancer treatment strategies, yet its predictive power and robustness need to be further verified with independent cohorts.

scholarly journals Distinctive Expression and Amplification of Genes at 11q13 in Relation to HPV Status with Impact on Survival in Head and Neck Cancer Patients

2018 ◽  
Vol 7 (12) ◽  
pp. 501 ◽  
Author(s):  
Francisco Hermida-Prado ◽  
Sofía Menéndez ◽  
Pablo Albornoz-Afanasiev ◽  
Rocío Granda-Diaz ◽  
Saúl Álvarez-Teijeiro ◽  
...  
Keyword(s):  
Protein Expression ◽  
Head And Neck ◽  
Gene Amplification ◽  
Hpv Infection ◽  
The Cancer Genome Atlas ◽  
Hpv Status ◽  
The Status ◽  
Impact On Survival ◽  
Cancer Genome Atlas ◽  
The Impact

Clear differences have been established between head and neck squamous cell carcinomas (HNSCC) depending on human papillomavirus (HPV) infection status. This study specifically investigated the status of the CTTN, CCND1 and ANO1 genes mapping at the 11q13 amplicon in relation to the HPV status in HNSCC patients. CTTN, CCND1 and ANO1 protein expression and gene amplification were respectively analyzed by immunohistochemistry and real-time PCR in a homogeneous cohort of 392 surgically treated HNSCC patients. The results were further confirmed using an independent cohort of 279 HNSCC patients from The Cancer Genome Atlas (TCGA). The impact on patient survival was also evaluated. CTTN, CCND1 and ANO1 gene amplification and protein expression were frequent in HPV-negative tumors, while absent or rare in HPV-positive tumors. Using an independent validation cohort of 279 HNSCC patients, we consistently found that these three genes were frequently co-amplified (28%) and overexpressed (39–46%) in HPV-negative tumors, whereas almost absent in HPV-positive tumors. Remarkably, these alterations (in particular CTTN and ANO1 overexpression) were associated with poor prognosis. Taken together, the distinctive expression and amplification of these genes could cooperatively contribute to the differences in prognosis and clinical outcome between HPV-positive and HPV-negative tumors. These findings could serve as the basis to design more personalized therapeutic strategies for HNSCC patients.

scholarly journals Immunogenomic Identification for Predicting the Prognosis of Cervical Cancer Patients

2021 ◽  
Vol 22 (5) ◽  
pp. 2442
Author(s):  
Qun Wang ◽  
Aurelia Vattai ◽  
Theresa Vilsmaier ◽  
Till Kaltofen ◽  
Alexander Steger ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Clinical Data ◽  
Regulatory Network ◽  
Univariate Analysis ◽  
Predictive Biomarkers ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Functional Enrichment ◽  
Wilcoxon Test

Cervical cancer is primarily caused by the infection of high-risk human papillomavirus (hrHPV). Moreover, tumor immune microenvironment plays a significant role in the tumorigenesis of cervical cancer. Therefore, it is necessary to comprehensively identify predictive biomarkers from immunogenomics associated with cervical cancer prognosis. The Cancer Genome Atlas (TCGA) public database has stored abundant sequencing or microarray data, and clinical data, offering a feasible and reliable approach for this study. In the present study, gene profile and clinical data were downloaded from TCGA, and the Immunology Database and Analysis Portal (ImmPort) database. Wilcoxon-test was used to compare the difference in gene expression. Univariate analysis was adopted to identify immune-related genes (IRGs) and transcription factors (TFs) correlated with survival. A prognostic prediction model was established by multivariate cox analysis. The regulatory network was constructed and visualized by correlation analysis and Cytoscape, respectively. Gene functional enrichment analysis was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). A total of 204 differentially expressed IRGs were identified, and 22 of them were significantly associated with the survival of cervical cancer. These 22 IRGs were actively involved in the JAK-STAT pathway. A prognostic model based on 10 IRGs (APOD, TFRC, GRN, CSK, HDAC1, NFATC4, BMP6, IL17RD, IL3RA, and LEPR) performed moderately and steadily in squamous cell carcinoma (SCC) patients with FIGO stage I, regardless of the age and grade. Taken together, a risk score model consisting of 10 novel genes capable of predicting survival in SCC patients was identified. Moreover, the regulatory network of IRGs associated with survival (SIRGs) and their TFs provided potential molecular targets.

scholarly journals NK Cell Regulation in Cervical Cancer and Strategies for Immunotherapy

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3104
Author(s):  
Adriana Gutiérrez-Hoya ◽  
Isabel Soto-Cruz
Keyword(s):  
Cervical Cancer ◽  
Nk Cells ◽  
Nk Cell ◽  
Hpv Infection ◽  
Cytolytic Activity ◽  
Cellular Immunotherapy ◽  
Antigen Receptors ◽  
Cytokines And Chemokines ◽  
Hpv Status ◽  
Infected Cells

Cervical cancer is one of the most prevalent gynaecological malignancies worldwide and is related to human papillomavirus (HPV) infection, viral persistence, progression, and invasion. Therefore, the immune response is linked to HPV status. Natural killer (NK) cells play a central role against virus-infected cells and tumours through a delicate balance between activating and inhibitory receptors and secretion of cytokines and chemokines. These cells also play a crucial role in tumour immunosurveillance. For these reasons, there is growing interest in harnessing NK cells as an immunotherapy for cervical cancer. These studies are diverse and include many strategies such as transferring activated autologous or allogeneic NK cells, improving the activation and cytolytic activity of NK cells using cytokines or analogues and modifying chimeric antigen receptors to increase specificity and targeting NK cells. However, research regarding the application of NK cells in immunotherapy is limited. This article focuses on recent discoveries about using NK cells to prevent and treat cervical cancer and the possibility of cellular immunotherapy becoming one of the best strategies to exploit the immune system to fight tumours.

scholarly journals High RPS27A Expression Predicts Poor Prognosis in Patients With HPV Type 16 Cervical Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Qiming Wang ◽  
Yan Cai ◽  
Xuewen Fu ◽  
Liang Chen
Keyword(s):  
Cervical Cancer ◽  
Poor Prognosis ◽  
Biological Significance ◽  
Enrichment Analysis ◽  
Hpv Infection ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Protein Protein Interaction ◽  
Cervical Cancer Cells ◽  
Cancer Genome Atlas

In recent years, the incidence and the mortality rate of cervical cancer have been gradually increasing, becoming one of the major causes of cancer-related death in women. In particular, patients with advanced and recurrent cervical cancers present a very poor prognosis. In addition, the vast majority of cervical cancer cases are caused by human papillomavirus (HPV) infection, of which HPV16 infection is the main cause and squamous cell carcinoma is the main presenting type. In this study, we performed screening of differentially expressed genes (DEGs) based on The Cancer Genome Atlas (TCGA) database and GSE6791, constructed a protein–protein interaction (PPI) network to screen 34 hub genes, filtered to the remaining 10 genes using the CytoHubba plug-in, and used survival analysis to determine that RPS27A was most associated with the prognosis of cervical cancer patients and has prognostic and predictive value for cervical cancer. The most significant biological functions and pathways of RPS27A enrichment were subsequently investigated with gene set enrichment analysis (GSEA), and integration of TCGA and GTEx database analyses revealed that RPS27A was significantly expressed in most cancer types. In this study, our analysis revealed that RPS27A can be used as a prognostic biomarker for HPV16 cervical cancer and has biological significance for the growth of cervical cancer cells.

scholarly journals The Prognostic Significance of MAFK and its Methylation in Cervical Cancer

2021 ◽  
Author(s):  
Mengjun Zhang ◽  
Hao Li ◽  
Yuan Liu ◽  
Siyu Hou ◽  
Ping Cui ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Aberrant Methylation ◽  
Cancer Data ◽  
Drug Candidates ◽  
Cancer Genome Atlas ◽  
Cancer Tissues

Abstract Background: The purpose of this study was to determine the value of MAFK as a biomarker of cervical cancer prognosis and to explore its methylation and possible cellular signaling pathways. Methods: We analyzed the cervical cancer data of The Cancer Genome Atlas (TCGA) through bioinformatics, including MAFK expression, methylation, prognosis and genome enrichment analysis. Results: MAFK expression was higher in cervical cancer tissues and was negatively correlated with the methylation levels of five CpG sites. MAFK is an independent prognostic factor of cervical cancer and is involved in the Nod-like receptor signaling pathway. CMap analysis screened four drug candidates for cervical cancer treatment. Conclusions: We confirmed that MAFK is a novel prognostic biomarker for cervical cancer and aberrant methylation may also affect MAFK expression and carcinogenesis. This study provides a new molecular target for the prognostic evaluation and treatment of cervical cancer.

scholarly journals Survival-Associated Metabolic Genes in Human Papillomavirus-Positive Head and Neck Cancers

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 253 ◽  
Author(s):  
Martin A. Prusinkiewicz ◽  
Steven F. Gameiro ◽  
Farhad Ghasemi ◽  
Mackenzie J. Dodge ◽  
Peter Y. F. Zeng ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Head And Neck ◽  
Patient Survival ◽  
Tricarboxylic Acid Cycle ◽  
Predictive Biomarkers ◽  
Head And Neck Cancers ◽  
The Cancer Genome Atlas ◽  
Metabolic Genes ◽  
Hpv Status ◽  
The Impact

Human papillomavirus (HPV) causes an increasing number of head and neck squamous cell carcinomas (HNSCCs). Altered metabolism contributes to patient prognosis, but the impact of HPV status on HNSCC metabolism remains relatively uncharacterized. We hypothesize that metabolism-related gene expression differences unique to HPV-positive HNSCC influences patient survival. The Cancer Genome Atlas RNA-seq data from primary HNSCC patient samples were categorized as 73 HPV-positive, 442 HPV-negative, and 43 normal-adjacent control tissues. We analyzed 229 metabolic genes and identified numerous differentially expressed genes between HPV-positive and negative HNSCC patients. HPV-positive carcinomas exhibited lower expression levels of genes involved in glycolysis and higher levels of genes involved in the tricarboxylic acid cycle, oxidative phosphorylation, and β-oxidation than the HPV-negative carcinomas. Importantly, reduced expression of the metabolism-related genes SDHC, COX7A1, COX16, COX17, ELOVL6, GOT2, and SLC16A2 were correlated with improved patient survival only in the HPV-positive group. This work suggests that specific transcriptional alterations in metabolic genes may serve as predictive biomarkers of patient outcome and identifies potential targets for novel therapeutic intervention in HPV-positive head and neck cancers.

scholarly journals The Impact of HPV DNA/p16 in Laryngeal/Hypopharyngeal Cancer: a Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
Sarah Van der Elst ◽  
Daniel P. Russo ◽  
Derek Mumaw ◽  
Michael Wotman ◽  
Tristan Tham
Keyword(s):  
Overall Survival ◽  
Meta Analysis ◽  
Hpv Infection ◽  
Hypopharyngeal Cancer ◽  
Cochrane Library ◽  
Hypopharyngeal Carcinoma ◽  
Hpv Dna ◽  
Pooled Data ◽  
Hpv Status ◽  
The Impact

AbstractBackgroundThis meta-analysis seeks to investigate the association between HPV and p16 status with overall survival in laryngeal and hypopharyngeal carcinoma.MethodsMedline, Scopus, EMBASE, and the Cochrane Library were used to identify studies for inclusion. Abstracts that discussed HPV/p16 status and prognosis in laryngeal or hypopharyngeal carcinoma were included. Next, full-text articles were screened and included based upon a checklist established a priori. Pooled hazard ratios for overall survival were generated using a random effects model. RevMan 5.3, Meta Essentials, and OpenMeta[Analyst] were used for statistical analysis.ResultsThirteen studies published between 2014 and 2019 with sample sizes ranging from 31 to 9,656 were selected for inclusion in this meta-analysis. The pooled data demonstrated that p16 status was not significantly associated with OS in either laryngeal or hypopharyngeal carcinoma with HRs of 1.03 (95% CI: 0.73–1.45; p = 0.88) and 1.02 (95% CI: 0.55–1.86; p = 0.96), respectively. The pooled data showed that HPV status was predictive of OS in laryngeal cancer with 0.63 (95% CI: 0.41–0.97; p = 0.03).ConclusionsOur results suggest that p16-positivity does not provide a survival benefit in LC and HPC. This is in contrast to studies in the oropharynx, where p16 status is a standard proxy for HPV infection and HPV infection is associated with improved prognosis.

p16 expression as a human papillomavirus (HPV)-independent prognostic biomarker in non-oropharyngeal squamous cell carcinoma (non-OPSCC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6007-6007 ◽  
Author(s):  
Christine H. Chung ◽  
Qiang Zhang ◽  
Christina Kong ◽  
Jonathan Harris ◽  
K. Kian Ang ◽  
...  
Keyword(s):  
Prognostic Biomarker ◽  
Surrogate Marker ◽  
Hpv Infection ◽  
Cox Models ◽  
Hazard Ratios ◽  
Hpv Status ◽  
N Stage ◽  
High Risk Hpv ◽  
P16 Expression

6007 Background: p16 is an important tumor suppressor and cell cycle regulator that is commonly lost in HPV-negative (-) and upregulated in HPV-positive (+) OPSCC. While the role of p16 expression in OPSCC as a surrogate marker of HPV infection and its association with prognosis are well established, its significance has not been studied in non-OPSCC including oral cavity, hypopharynx and larynx, where HPV infection is rare. We hypothesize that p16 expression is a prognostic biomarker of favorable outcome (progression-free and overall survival) in non-OPSCC. Methods: p16 expression in non-OPSCC from RTOG 0129, 0234 and 0522 was determined by immunohistochemistry (p16 mouse monoclonal antibody, prediluted, MTM-CINtech, 9518) and considered positive if >70% of the tumor cells demonstrated diffuse staining. The high risk HPV status in non-OPSCC from RTOG 0129 and 0522 was determined by in situ hybridization using a cocktail probe including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 66. Hazard ratios from Cox models were expressed as positive/negative, stratified by trial, and adjusted for age, gender, T, and N stage. Results: p16 expression was positive in 14.1% (12/85), 24.2% (23/95) and 19.0% (27/142) of non-OPSCC from RTOG 0129, RTOG 0234, and RTOG 0522, respectively. HPV ISH was positive in 6.5% (6/93) and 6.9% (7/101) of non-OPSCC from RTOG 0129 and RTOG 0522, respectively. There was moderate agreement between p16 and HPV status (kappa=0.53). The hazard ratios for p16 expression are 0.63 (p=0.03) and 0.56 (p=0.01) for PFS and OS, respectively. In 0522, there was no interaction between p16 status and two treatment arms (RT+cisplatin+/-cetuximab). In comparison of OPSCC and non-OPSCC, patients with p16(+) OPSCC have better PFS and OS than patients with p16(+) non-OPSCC, but patients with p16(-) OPSCC and non-OPSCC have similar outcomes. Conclusions: Similar to results in patients with OPSCC, patients with p16(+) non-OPSCC have better outcomes than patients with p16(-); however, the differential appears smaller than has been observed in HPV(+) OPSCC. Further studies are warranted to delineate the role of p16 expression as a prognostic biomarker in non-OPSCC and OPSCC. Clinical trial information: NCT00265941, NCT00047008, NCT00084318.

Sign in / Sign up

Export Citation Format

Share Document