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Frontiers in Bioscience (Landmark... Jun 2024The incidence rate of oropharyngeal squamous cell carcinoma (OPSCC) worldwide is alarming. In the clinical community, there is a pressing necessity to comprehend the...
BACKGROUND
The incidence rate of oropharyngeal squamous cell carcinoma (OPSCC) worldwide is alarming. In the clinical community, there is a pressing necessity to comprehend the etiology of the OPSCC to facilitate the administration of effective treatments.
METHODS
This study confers an integrative genomics approach for identifying key oncogenic drivers involved in the OPSCC pathogenesis. The dataset contains RNA-Sequencing (RNA-Seq) samples of 46 Human papillomavirus-positive head and neck squamous cell carcinoma and 25 normal Uvulopalatopharyngoplasty cases. The differential marker selection is performed between the groups with a log2FoldChange (FC) score of 2, adjusted -value < 0.01, and screened 714 genes. The Particle Swarm Optimization (PSO) algorithm selects the candidate gene subset, reducing the size to 73. The state-of-the-art machine learning algorithms are trained with the differentially expressed genes and candidate subsets of PSO.
RESULTS
The analysis of predictive models using Shapley Additive exPlanations revealed that seven genes significantly contribute to the model's performance. These include , , and , which predominantly influence differentiating between sample groups. They were followed in importance by , , , and . The Random Forest and Bayes Net algorithms also achieved perfect validation scores when using PSO features. Furthermore, gene set enrichment analysis, protein-protein interactions, and disease ontology mining revealed a significant association between these genes and the target condition. As indicated by Shapley Additive exPlanations (SHAPs), the survival analysis of three key genes unveiled strong over-expression in the samples from "The Cancer Genome Atlas".
CONCLUSIONS
Our findings elucidate critical oncogenic drivers in OPSCC, offering vital insights for developing targeted therapies and enhancing understanding its pathogenesis.
Topics: Humans; Oropharyngeal Neoplasms; Biomarkers, Tumor; Papillomavirus Infections; Artificial Intelligence; Gene Expression Regulation, Neoplastic; Squamous Cell Carcinoma of Head and Neck; Algorithms; Sequence Analysis, RNA; Machine Learning; Papillomaviridae; Carcinoma, Squamous Cell
PubMed: 38940026
DOI: 10.31083/j.fbl2906220 -
Viruses Jun 2024HPV16 is responsible for approximately 60% and 90% of global HPV-induced cervical and oropharyngeal cancers, respectively. HPV16 intratype variants have been identified... (Review)
Review
HPV16 is responsible for approximately 60% and 90% of global HPV-induced cervical and oropharyngeal cancers, respectively. HPV16 intratype variants have been identified by HPV genome sequencing and classified into four phylogenetic lineages (A-D). Our understanding of HPV16 variants mostly derives from epidemiological studies on cervical cancer (CC) in which HPV16 B, C, and D lineages (previously named "non-European" variants) were mainly associated with high-grade cervical lesions and cancer. Although a predominance of HPV16 lineage A (previously named "European variants") has been observed in head and neck squamous cell carcinoma (HNSCC), epidemiological and in vitro biological studies are still limited for this tumor site. Next Generation Sequencing (NGS) of the entire HPV genome has deepened our knowledge of the prevalence and distribution of HPV variants in CC and HNSCC. Research on cervical cancer has shown that certain HPV16 sublineages, such as D2, D3, A3, and A4, are associated with an increased risk of cervical cancer, and sublineages A4, D2, and D3 are linked to a higher risk of developing adenocarcinomas. Additionally, lineage C and sublineages D2 or D3 of HPV16 show an elevated risk of developing premalignant cervical lesions. However, it is still crucial to conduct large-scale studies on HPV16 variants in different HPV-related tumor sites to deeply evaluate their association with disease development and outcomes. This review discusses the current knowledge and updates on HPV16 phylogenetic variants distribution in HPV-driven anogenital and head and neck cancers.
Topics: Humans; Papillomavirus Infections; Phylogeny; Head and Neck Neoplasms; Human papillomavirus 16; Female; Genetic Variation; Uterine Cervical Neoplasms; Genome, Viral; Anus Neoplasms; Male; Squamous Cell Carcinoma of Head and Neck
PubMed: 38932197
DOI: 10.3390/v16060904 -
Journal of Medical Virology Jun 2024
Topics: Humans; Oropharyngeal Neoplasms; Papillomavirus Infections; Chemoradiotherapy; Prognosis; Aged; Radiotherapy; Aged, 80 and over; Papillomaviridae
PubMed: 38922943
DOI: 10.1002/jmv.29535 -
Cells Jun 2024Head and neck cancers rank as the sixth most prevalent cancers globally. In addition to traditional risk factors such as smoking and alcohol use, human papillomavirus...
Head and neck cancers rank as the sixth most prevalent cancers globally. In addition to traditional risk factors such as smoking and alcohol use, human papillomavirus (HPV) infections are becoming a significant causative agent of head and neck cancers, particularly among Western populations. Although HPV offers a significant survival benefit, the search for better biomarkers is still ongoing. In the current study, our objective was to investigate whether the expression levels of three PDZ-domain-containing proteins (SCRIB, NHERF2, and DLG1), known HPV E6 cellular substrates, influence the survival of HNSCC patients treated by primary surgery (n = 48). Samples were derived from oropharyngeal and oral cancers, and HPV presence was confirmed by PCR and p16 staining. Clinical and follow-up information was obtained from the hospital database and the Croatian Cancer registry up to November 2023. Survival was evaluated using the Kaplan-Meier method and Cox proportional hazard regression. The results were corroborated through the reanalysis of a comparable subset of TCGA cancer patients (n = 391). In conclusion, of the three targets studied, only SCRIB levels were found to be an independent predictor of survival in the Cox regression analysis, along with tumor stage. Further studies in a more typical Western population setting are needed since smoking and alcohol consumption are still prominent in the Croatian population, while the strongest association between survival and SCRIB levels was seen in HPV-negative cases.
Topics: Humans; Male; Female; Prognosis; Tumor Suppressor Proteins; Middle Aged; Membrane Proteins; Papillomavirus Infections; Papillomaviridae; Aged; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Biomarkers, Tumor; Kaplan-Meier Estimate; Adult
PubMed: 38920638
DOI: 10.3390/cells13121002 -
BMC Oral Health Jun 2024Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and...
BACKGROUND
Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and succumb to the disease; thus, there is a need for biomarkers identifying these patients for intensified treatment. Leucine-rich repeats and immunoglobulin-like domain (LRIG) protein 1 is a negative regulator of receptor tyrosine kinase signaling and a positive prognostic factor in OPSCC. Studies indicate that LRIG1 interacts with the LIM domain 7 protein (LMO7), a stabilizer of adherence junctions. Its role in OPSCC has not been studied before.
METHODS
A total of 145 patients diagnosed with OPSCC were enrolled. Immunohistochemical LMO7 expression and staining intensity were evaluated in the tumors and correlated with known clinical and pathological prognostic factors, such as HPV status and LRIG1, CD44, Ki67, and p53 expression.
RESULTS
Our results show that high LMO7 expression is associated with significantly longer overall survival (OS) (p = 0.044). LMO7 was a positive prognostic factor for OS in univariate analysis (HR 0.515, 95% CI: 0.267-0.994, p = 0.048) but not in multivariate analysis. The LMO7 expression correlated with LRIG1 expression (p = 0.048), consistent with previous findings. Interestingly, strong LRIG1 staining intensity was an independent negative prognostic factor in the HPV-driven group of tumors (HR 2.847, 95% Cl: 1.036-7.825, p = 0.043).
CONCLUSIONS
We show for the first time that high LMO7 expression is a positive prognostic factor in OPSCC, and we propose that LMO7 should be further explored as a biomarker. In contrast to previous reports, LRIG1 expression was shown to be an independent negative prognostic factor in HPV-driven OPSCC.
Topics: Humans; Oropharyngeal Neoplasms; Male; Female; Middle Aged; Prognosis; LIM Domain Proteins; Biomarkers, Tumor; Carcinoma, Squamous Cell; Aged; Transcription Factors; Membrane Glycoproteins; Adult; Ki-67 Antigen; Hyaluronan Receptors; Tumor Suppressor Protein p53; Papillomavirus Infections; Immunohistochemistry; Aged, 80 and over; Survival Rate
PubMed: 38918827
DOI: 10.1186/s12903-024-04510-4 -
BMC Cancer Jun 2024Psychosocial factors and socioeconomic status have been associated with incidence, survival, and quality of life among patients with head and neck cancer. We...
BACKGROUND
Psychosocial factors and socioeconomic status have been associated with incidence, survival, and quality of life among patients with head and neck cancer. We investigated the association between different psychosocial factors, socioeconomic status, and patient delays in T3-T4 oral, oropharyngeal, and laryngeal cancer.
PATIENTS AND METHODS
We conducted a nationwide prospective questionnaire-based study (n = 203) over a 3-year period.
RESULTS
We found no association between psychosocial factors (depression, social isolation, loneliness, and cynical hostility) and patient delay. Depression was three times more common among head and neck cancer patients compared with the general Finnish population. Head and neck cancer patients had lower educational levels and employment status, and were more often current smokers and heavy drinkers.
CONCLUSIONS
Although we found no association between patient delay and psychosocial factors, patients diagnosed with a large head and neck cancer appeared to have a lower socioeconomic status and higher risk for developing depression, which should be considered in clinical practice.
Topics: Humans; Male; Female; Laryngeal Neoplasms; Middle Aged; Oropharyngeal Neoplasms; Aged; Surveys and Questionnaires; Prospective Studies; Depression; Mouth Neoplasms; Adult; Quality of Life; Finland; Social Class; Neoplasm Staging; Socioeconomic Factors; Time-to-Treatment
PubMed: 38914952
DOI: 10.1186/s12885-024-12517-x -
Scientific Reports Jun 2024Several studies have emphasised how positive and negative human papillomavirus (HPV+ and HPV-, respectively) oropharyngeal squamous cell carcinoma (OPSCC) has...
Several studies have emphasised how positive and negative human papillomavirus (HPV+ and HPV-, respectively) oropharyngeal squamous cell carcinoma (OPSCC) has distinct molecular profiles, tumor characteristics, and disease outcomes. Different radiomics-based prediction models have been proposed, by also using innovative techniques such as Convolutional Neural Networks (CNNs). Although some of these models reached encouraging predictive performances, there evidence explaining the role of radiomic features in achieving a specific outcome is scarce. In this paper, we propose some preliminary results related to an explainable CNN-based model to predict HPV status in OPSCC patients. We extracted the Gross Tumor Volume (GTV) of pre-treatment CT images related to 499 patients (356 HPV+ and 143 HPV-) included into the OPC-Radiomics public dataset to train an end-to-end Inception-V3 CNN architecture. We also collected a multicentric dataset consisting of 92 patients (43 HPV+ , 49 HPV-), which was employed as an independent test set. Finally, we applied Gradient-weighted Class Activation Mapping (Grad-CAM) technique to highlight the most informative areas with respect to the predicted outcome. The proposed model reached an AUC value of 73.50% on the independent test. As a result of the Grad-CAM algorithm, the most informative areas related to the correctly classified HPV+ patients were located into the intratumoral area. Conversely, the most important areas referred to the tumor edges. Finally, since the proposed model provided additional information with respect to the accuracy of the classification given by the visualization of the areas of greatest interest for predictive purposes for each case examined, it could contribute to increase confidence in using computer-based predictive models in the actual clinical practice.
Topics: Humans; Oropharyngeal Neoplasms; Tomography, X-Ray Computed; Neural Networks, Computer; Papillomavirus Infections; Male; Female; Papillomaviridae; Middle Aged; Aged; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Tumor Burden; Human Papillomavirus Viruses
PubMed: 38902523
DOI: 10.1038/s41598-024-65240-9 -
Cancer Epidemiology Jun 2024France has the sixth highest incidence of oropharyngeal cancer (OPC) in Europe, but the epidemiological impact of high-risk HPV (HR-HPV) remains poorly documented. The...
BACKGROUND
France has the sixth highest incidence of oropharyngeal cancer (OPC) in Europe, but the epidemiological impact of high-risk HPV (HR-HPV) remains poorly documented. The objective of our study was to assess the proportion of OPCs caused by HR-HPV in Paris, and its suburbs, over the four past decades. This area accounts for almost one-fifth of the total population of France.
METHODS
OPCs diagnosed in 1981, 1986, 1991, 1996, 2001, 2006, 2011, 2016 and 2020/2021 in two of the main referral cancer centers for HNCs in Paris and its suburbs were retrieved from the tumor biobanks. HPV status was determined by p16-staining and HPV-DNA detection. Samples were considered HPV-driven if both assays were positive. Results were compared to the French cancer registry data.
RESULTS
Samples from 697 OPC patients were assessed (including 82 % of all samples diagnosed in 2001, 2006, 2011, 2016, 2021). The proportion of HPV-driven cases rose from 2.7 % to 53 % between 1981 and 2021. HPV16 was the dominant genotype during the study period. Of patients with HPV-driven OPC, 81 % were male and 42 % were smokers versus 80 % and 92 % in their HPV-negative counterparts. The age of OPC patients increased significantly, during the study period, independent of their HPV status CONCLUSION: The proportion of HPV-driven OPCs has significantly increased in Paris and its suburbs, during the last four decades. OPCs has become the 2nd predominant type of head and neck cancer, in France. This may be linked to the rise in HPV-driven cases and the decrease of tobacco and alcohol consumption in men.
PubMed: 38901087
DOI: 10.1016/j.canep.2024.102603 -
Scientific Reports Jun 2024The increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) is primarily due to human papillomavirus, and understanding the tumor biology caused by the...
The increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) is primarily due to human papillomavirus, and understanding the tumor biology caused by the virus is crucial. Our goal was to investigate the proteins present in the serum of patients with OPSCC, which were not previously studied in OPSCC tissue. We examined the difference in expression of these proteins between HPV-positive and -negative tumors and their correlation with clinicopathological parameters and patient survival. The study included 157 formalin-fixed, paraffin-embedded tissue samples and clinicopathological data. Based on the protein levels in the sera of OPSCC patients, we selected 12 proteins and studied their expression in HPV-negative and HPV-positive OPSCC cell lines. LRG1, SDR16C5, PIP4K2C and MVD proteins were selected for immunohistochemical analysis in HPV-positive and -negative OPSCC tissue samples. These protein´s expression levels were compared with clinicopathological parameters and patient survival to investigate their clinical relevance. LRG1 expression was strong in HPV-negative whereas SDR16C5 expression was strong in HPV-positive tumors. Correlation was observed between LRG1, SDR16C5, and PIP4K2C expression and patient survival. High expression of PIP4K2C was found to be an independent prognostic factor for overall survival and expression correlated with HPV-positive tumor status. The data suggest the possible role of LRG1, SDR16C5 and PIP4K2C in OPSCC biology.
Topics: Humans; Male; Oropharyngeal Neoplasms; Female; Middle Aged; Aged; Papillomavirus Infections; Glycoproteins; Carcinoma, Squamous Cell; Biomarkers, Tumor; Squamous Cell Carcinoma of Head and Neck; Papillomaviridae; Adult; Prognosis; Cell Line, Tumor
PubMed: 38898137
DOI: 10.1038/s41598-024-64823-w -
Head and Neck Pathology Jun 2024Mixed neuroendocrine-nonneuroendocrine (MiNEN) neoplasms in the head and neck are exceptionally rare biphasic tumors with unclear pathogenesis and an aggressive clinical... (Review)
Review
Mixed neuroendocrine-nonneuroendocrine (MiNEN) neoplasms in the head and neck are exceptionally rare biphasic tumors with unclear pathogenesis and an aggressive clinical behavior. This is the first reported case of an oropharyngeal MiNEN with the nonneuroendocrine component being an HPV-associated adenocarcinoma. The tumor arose in a 56 year-old male with history of long-term cigarette smoking and was composed of an adenocarcinoma intermixed with a small cell neuroendocrine carcinoma. P16 immunohistochemical stain and HPV16/18 in-situ hybridization were strongly and diffusely expressed in both components.
Topics: Humans; Male; Middle Aged; Oropharyngeal Neoplasms; Carcinoma, Neuroendocrine; Adenocarcinoma; Papillomavirus Infections; Neoplasms, Complex and Mixed; Biomarkers, Tumor
PubMed: 38896312
DOI: 10.1007/s12105-024-01660-3