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.
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http://dx.doi.org/10.3892/ol.2021.12550 | DOI Listing |
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. HPV-negative HNSCC, which arises in the upper airway mucosa, is particularly aggressive, with nearly half of patients succumbing to the disease within five years and limited response to immune checkpoint inhibitors compared to other cancers. There is a need to further explore the complex immune landscape in HPV-negative HNSCC to identify potential therapeutic targets.
View Article and Find Full Text PDFHead Neck
January 2025
Department of Otolaryngology-Head and Neck Surgery, West Virginia University, Morgantown, West Virginia, USA.
Background: Human papillomavirus (HPV) negative oropharyngeal squamous cell carcinoma (OPSCC) is associated with worse survival when compared to HPV-positive OPSCC. Primary surgery is one option to intensify therapy in this high-risk group of patients. Unfortunately, the only randomized trial to explore this approach (RTOG 1221) failed to accrue and the role of primary surgery in the treatment of HPV-negative OPSCC remains unanswered.
View Article and Find Full Text PDFArch Oral Biol
January 2025
Department of Microbiology, KS Hegde Medical Academy, Nitte (Deemed to be University), Deralakatte, Mangaluru 575018, India. Electronic address:
Objective: The study assessed the prevalence and clinical implications of Epstein Barr Virus (EBV)-positive but Human Papillomavirus (HPV)-negative oral squamous cell carcinoma (OSCC) in a tertiary care hospital setting. The overall goal was to elucidate the potential impact of EBV on OSCC disease progression and prognosis.
Design: A total of 134 surgically resected and histopathologically confirmed OSCC tumor biopsies were collected from a tertiary care hospital.
Viruses
December 2024
Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA 02115, USA.
Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HPV-positive HNSCC) has distinct biological characteristics from HPV-negative HNSCC. Using an AI-based analytical platform on meta cohorts, we profiled expression patterns of viral transcripts and HPV viral genome integration, and classified the tumor microenvironment (TME). Unsupervised clustering analysis revealed five distinct and novel TME subtypes across patients (immune-enriched, highly immune and B-cell enriched, fibrotic, immune-desert, and immune-enriched luminal).
View Article and Find Full Text PDFCancers (Basel)
January 2025
Head and Neck Oncology Group, Centre for Host Microbiome Interaction, King's College London, Hodgkin Building, London SE1 1UL, UK.
Background: Cancer-associated fibroblasts have been reported to play a central role in driving cancer progression, promoting metastasis, and conferring resistance to therapy in HNSCC.
Methods: Indirect and direct co-culture models of HPV-positive and HPV-negative HNSCC cells with fibroblasts were developed to study the effect of fibroblasts on cancer cells. ELISA was used to measure IL-6 secretion in these models.
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