Prevalence of HPV in Mexican Patients with Head and Neck Squamous Carcinoma and Identification of Potential Prognostic Biomarkers.
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ABSTRACT:
SUBMITTER: Mendez-Matias G
PROVIDER: S-EPMC8616077 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Human papillomavirus (HPV) is an accepted cause of head and neck squamous cell carcinoma (HNSCC), and patients with HPV-associated HNSCC have a favorable prognosis. Currently, there is no general guidance on the most appropriate biomarkers for clinical assessment of HPV in these malignancies. We compared PCR-based and serologic HPV assays, as well as p16 immunohistochemistry, individually and in combination in a single population-based study to assess their associations with overall survival among patients with HNSCC, and thus their potential value as biomarkers. HPV16 serology was determined for 488 patients; immunohistochemical detection of p16 expression in tumors was conducted in a subset of 233 cases, and PCR-based methods to assess the presence of HPV16 DNA in a subset of 179 cases of tumors. Considering each biomarker individually in the subset of patients studied for all endpoints, seropositivity for the E6 and E7 proteins was significantly associated with enhanced all-cause survival in oropharyngeal disease [HR(E6/E7+) = 0.1, 95% confidence interval (CI) = 0.02-0.3]. Neither the presence of HPV16 DNA nor p16 immunostaining was associated with significant enhanced overall survival in oropharyngeal disease (HR(DNA) = 0.9, 95% CI = 0.3-2.9; HR(p16) = 0.3, 95% CI = 0.1-1.1). However, the combination of HPV-positive DNA and E6 or E7 serology was associated with enhanced overall survival in oropharyngeal disease (HR(DNA+/E6/E7+) = 0.1, 95% CI = 0.02-1.0), whereas E6/E7 seronegative patients with evidence of HPV in tumor DNA did not show any evidence of favorable survival (HR(DNA+/E6-/E7-) = 3.4, 95% CI = 0.6-18.1). Furthermore, patients with p16 staining and E6 or E7 seropositivity had favorable survival from oropharyngeal disease (HR(p16+/E6/E7+) = 0.1, 95% CI = 0.02-0.4), whereas patients who were p16 positive and E6/E7 seronegative had significantly increased hazard of all causes of death (HR(p16+/E6-/E7-) = 3.1, 95% CI = 1.2-7.7). A stronger association of HPV presence with prognosis (assessed by all-cause survival) is observed when "HPV-associated" HNSCC is defined using tumor status (HPV DNA status or P16) and HPV E6/E7 serology in combination rather using tumor HPV status alone.
| S-EPMC3463756 | biostudies-literature
Project description:BackgroundAs a type of malignant tumor, head and neck squamous cell carcinoma (HNSCC) seriously threatens human health. This study is aimed at constructing a new, reliable prognostic model.MethodThe gene expression profile data of HNSCC patients were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas databases. The immune-related differentially expressed genes (IRDEGs) related to HNSCC were identified. We then used Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis to explore IRDEGs related to the HNSCC prognosis and to construct and validate a risk scoring model and used ESTIMATE to evaluate tumor immune infiltration in HNSCC patients. Finally, we validated IGSF5 expression and function in HNSCC cells.ResultsA total of 1,195 IRDEGs were found from the GSE65858 dataset. Thirty-one of the 1,195 IRDEGs were associated with the prognosis of HNSCC. Nine key IRDEGs were further selected using the LASSO method, and a risk scoring model was established for predicting the survival of HNSCC patients. According to the risk scoring model, the prognosis of patients in the high-risk group was worse than that of the low-risk group; the high-risk group had significantly higher immune scores than the low-risk group; and between the high- and low-risk samples, there were significant differences in the proportion of 10 types of cells, including naive cells, plasma cells, and resting CD4+ memory T cells. IGSF5 has low expression in HNSCC, and overexpression of IGSF5 significantly impaired HNSCC cell proliferation.ConclusionThis prognostic risk assessment model can help systematically evaluate the survival prognosis of HNSCC patients and provides a new research direction for the improvement of the survival prognosis of HNSCC patients in clinical practice.
| S-EPMC7810542 | biostudies-literature
Project description:Head and neck squamous cell carcinomas (HNSCCs) are highly aggressive tumors with rapid progression and poor prognosis. Human papillomavirus (HPV) infection has been identified as one of the most important carcinogens for HNSCC. As an early event in HNSCC, infection with HPV leads to altered immune profiles in the tumor microenvironment (TME). The TME plays a key role in the progression and transformation of HNSCC. However, the TME in HNSCC is a complex and heterogeneous mix of tumor cells, fibroblasts, different types of infiltrating immune cells, and extracellular matrix. Biomarkers relevant to the TME, and the biological role of these biomarkers, remain poorly understood. To this end, we performed comprehensive analysis of the RNA sequencing (RNA-Seq) data from tumor tissue of 502 patients with HNSCC and healthy tissue of 44 control samples. In total, we identified 4,237 differentially expressed genes, including 2,062 upregulated and 2,175 downregulated genes. Further in-depth bioinformatic analysis suggested 19 HNSCC tumor tissue-specific genes. In the subsequent analysis, we focused on the biomarker candidates shown to be significantly associated with unfavorable patient survival: ITGA5, PLAU, PLAUR, SERPINE1, TGFB1, and VEGFC. We found that the expression of these genes was negatively regulated by DNA methylation. Strikingly, all of these potential biomarkers are profoundly involved in the activation of the epithelial-mesenchymal transition (EMT) pathway in HNSCCs. In addition, these targets were found to be positively correlated with the immune invasion levels of CD4+ T cells, macrophages, neutrophils, and dendritic cells, but negatively correlated with B-cell infiltration and CD8+ T-cell invasion. Notably, our data showed that the expression levels of ITGA5, PLAU, PLAUR, SERPINE1, and TGFB1 were significantly overexpressed in HPV-positive HNSCCs compared to normal controls, indicating the potential role of these biomarkers as transformation and/or malignant progression markers for HNSCCs in patients with HPV infection. Taken together, the results of our study propose ITGA5, PLAU, PLAUR, SERPINE1, and TGFB1 as potential prognostic biomarkers for HNSCCs, which might be involved in the HPV-related TME remodeling of HNSCC. Our findings provide important implications for the development and/or improvement of patient stratification and customized immunotherapies in HNSCC.
| S-EPMC9679011 | biostudies-literature
Project description:Head and neck squamous cell carcinoma (HNSCC) comprise a group of malignant tumors arising from the squamous epithelium of the oral cavity, pharynx, and larynx. HNSCC is the 6th most common cancer in the world, with approximately 650,000 new cases and 400,000 deaths annually. Although survival rates have improved, HNSCC therapy may result in short - or long-term morbidity in approximately 50% of cases. Previous studies have also indicated that the overexpression of procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenases (PLOD) family proteins could lead to certain diseases or even tumors. However, there has been no dedicated evaluation of the relationship between PLOD family members and HNSCC. Here we used data from the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA) databases to explore the potential role of PLOD family proteins in HNSCC. Our evaluations suggest that increased expression of PLOD family proteins may be associated with poorer prognosis and increased immune infiltration in HNSCC, making these proteins a potential biomarker for personalized treatment of HNSCC.
| S-EPMC9937984 | biostudies-literature
Project description:Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous disease that affects more than 800,000 patients worldwide each year. The variability of HNSCC is associated with differences in the carcinogenesis processes that are caused by two major etiological agents, namely, alcohol/tobacco, and human papillomavirus (HPV). Compared to non-virally induced carcinomas, the oropharyngeal tumors associated with HPV infection show markedly better clinical outcomes and are characterized by an immunologically “hot” landscape with high levels of tumor-infiltrating lymphocytes. However, the standard of care remains the same for both HPV-positive and HPV-negative HNSCC. Surprisingly, treatment de-escalation trials have not shown any clinical benefit in patients with HPV-positive tumors to date, most likely due to insufficient patient stratification. The in-depth analysis of the immune response, which places an emphasis on tumor-infiltrating immune cells, is a widely accepted prognostic tool that might significantly improve both the stratification of HNSCC patients in de-escalation trials and the development of novel immunotherapeutic approaches.
| S-EPMC7522596 | biostudies-literature
Project description:Background: Head and neck squamous carcinoma (HNSC) poses a major threat to human life. The role of human papillomavirus (HPV) infection in the initiation and progression of HNSC is becoming more widely accepted. HPV-positive (HPV+) HNSC has shown unique responses to cancer therapies, which may be due to differences in immune cell infiltration. It is critical to determine how the immune responses to HPV in HNSC are regulated. Methods: Transcriptome data of HNSC from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database were analyzed. Then, the CIBERSORT algorithm was used to calculate immune cell infiltration in HNSC. FDCSP expression level was detected by qPCR in the HNSC tissues collected from the Nanfang Hospital. Results: Follicular dendritic cell secreted protein (FDCSP) was highly expressed in HPV+ HNSC, and higher expression of FDSCP was associated with a favorable prognosis. In HPV+ HNSC samples, FDCSP significantly increased the proportion of T follicular helper cells (TFHs). FDCSP expression was also found to be associated with TP53 mutation status in HPV+ HNSC. The function of FDCSP was intimately connected to chemokine pathways, particularly with the C-X-C motif chemokine ligand 13 (CXCL13). We verified that the high expression of FDCSP in HPV+ HNSC and higher FDCSP is closely related to prognosis in HNSC samples we collected by qPCR. Conclusions: Collectively, these findings may provide fresh evidence that FDCSP is a potential chemokine-associated prognostic biomarker in HPV+ HNSC.
| S-EPMC9599724 | biostudies-literature
Project description:HPV-associated head and neck squamous cell carcinoma (HNSCC) is a cancer entity with unique biological and clinical characteristics that requires more personalized treatment strategies. As the backbone of conventional therapeutics, radiation is now harnessed to synergize with immunotherapy in multiple malignancies. Accumulating preclinical and clinical data have suggested the potential of radioimmunotherapy in eliciting local and systemic anti-tumor response via direct killing of tumor cells and immunogenic cell death. However, this effect remains uncertain in HPV-associated HNSCC. Owing to its intrinsic radiosensitivity and distinct tumor microenvironment, HPV-associated HNSCC may represent a good candidate for radioimmunotherapy. In this review, we provide a detailed illustration of the biology, the genomic features, and immune landscapes of HPV-associated HNSCC that support the synergism between radiation and immune agents. The interaction between radiotherapy and immunotherapy is described. We also highlight the present evidence as well as ongoing trials using different combination strategies in the recurrent/metastatic or definitive settings. In addition, we have summarized the challenges and outlook for future trial design, with special emphasis on radiotherapy optimization and novel therapeutic options to incorporate.
| S-EPMC9405566 | biostudies-literature
Project description:The prognosis of patients with human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is poorer than those with HPV-positive HNSCC. The present study aimed to identify novel and specific biomarkers of HPV-negative HNSCC using bioinformatics analysis and associated experiments. The gene expression profiles of HPV-negative HNSCC tissues and corresponding clinical data were downloaded from The Cancer Genome Atlas database and used in a weighted gene co-expression network analysis. Genes in clinically significant co-expression modules were used to construct a protein-protein interaction (PPI) network. The genes demonstrating a high degree score in the PPI network and a high correlation with tumor grade were considered hub genes. The diagnostic value of the hub genes associated with HPV-negative and HPV-positive HNSCC was analyzed using differential expression gene (DEG) analysis, immunohistochemical (IHC) staining and a receiver operating characteristic (ROC) curve analysis. Seven genes [Serrate RNA effector molecule (SRRT), checkpoint kinase 2 (CHEK2), small nuclear ribonucleoprotein polypeptide E (SNRPE), proteasome 26S subunit ATPase 2 (PSMC2), origin recognition complex subunit 5 (ORC5), S100 calcium binding protein A7 and keratinocyte differentiation associated protein (KRTDAP)] were demonstrated to be hub genes in clinically significant co-expression modules. DEG, IHC and ROC curve analyses revealed that SRRT, CHEK2 and SNRPE were significantly upregulated in HPV-negative and HPV-positive HNSCC tissues compared with in adjacent tissues, and these genes demonstrated a high diagnostic value for distinguishing HNSCC tissues. However, PSMC2, ORC5 and KRTDAP were the only differentially expressed genes identified in HPV-negative HNSCC tissues, and these genes demonstrated a high diagnostic value for HPV-negative HNSCC. PSMC2, ORC5 and KRTDAP may therefore serve as novel and specific biomarkers for HPV-negative HNSCC, potentially improving the diagnosis and treatment of patients with HPV-negative HNSCC.
| S-EPMC7905686 | biostudies-literature
Project description:PurposeThe evolutionary-conserved Wnt/β-CATENIN (WBC) pathway has been implicated in the pathogenesis of different solid malignant tumors. We evaluated the prognostic relevance of β-CATENIN, a pivotal mediator of WBC activation, in patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC).MethodsWe analyzed if patients with HPV-positive HNSCC from the "The Cancer Genome Atlas" (TCGA cohort, n = 41) can be stratified based on their CTNNB1 mRNA expression. Moreover, in a tissue microarray (TMA) of primary tumor sections from HPV-positive HNSCC patients treated in a tertiary academic center (in-house cohort, n = 31), we evaluated the prognostic relevance of β-CATENIN expression on protein level.ResultsIn silico mining of CTNNB1 expression in HPV-positive HNSCC revealed that high CTNNB1 expression was linked to better overall survival (OS, p = 0.062). Moreover, high β-CATENIN expression was significantly associated with a better OS in our in-house cohort (p = 0.035).ConclusionBased on these findings, we postulate that β-CATENIN expression could serve (potentially in conjunction with other WBC pathway members) as a marker for better survival outcomes in patients with HPV-positive HNSCC. However, it is evident that future studies on bigger cohorts are warranted.
| S-EPMC10374714 | biostudies-literature
Project description:DNA methylation plays an important role in the etiology and pathogenesis of head and neck squamous cell carcinoma (HNSCC). The current study aimed to identify aberrantly methylated-differentially expressed genes (DEGs) by a comprehensive bioinformatics analysis. In addition, we screened for DEGs affected by DNA methylation modification and further investigated their prognostic values for HNSCC. We included microarray data of DNA methylation (GSE25093 and GSE33202) and gene expression (GSE23036 and GSE58911) from Gene Expression Omnibus. Aberrantly methylated-DEGs were analyzed with R software. The Cancer Genome Atlas (TCGA) RNA sequencing and DNA methylation (Illumina HumanMethylation450) databases were utilized for validation. In total, 27 aberrantly methylated genes accompanied by altered expression were identified. After confirmation by The Cancer Genome Atlas (TCGA) database, 2 hypermethylated-low-expression genes (FAM135B and ZNF610) and 2 hypomethylated-high-expression genes (HOXA9 and DCC) were identified. A receiver operating characteristic (ROC) curve confirmed the diagnostic value of these four methylated genes for HNSCC. Multivariate Cox proportional hazards analysis showed that FAM135B methylation was a favorable independent prognostic biomarker for overall survival of HNSCC patients.
| S-EPMC6140809 | biostudies-other