Project description:To investigate the differences of transcriptional activities between oropharyngeal squamous cell caricnoma and small cell carcinoma, we performed a transcriptomic analysis using high throoughput RNA sequencing (RNA-seq).
Project description:Genome wide DNA methylation profiling of normal and primary oropharyngeal squamous cell carcinoma tissue samples, some infected with the human papilloma virus (HPV). The Illumina Infinium 27k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 27,000 CpGs in tissue samples. Samples included 46 oropharyngeal SCC primary tumors and 46 normal adjacent mucosal samples. For each tumor sample, HPV status (positivity based on both DNA and E6/E7 RNA) and p16 immunohistochemistry status is included. Bisulphite converted DNA from the 46 primary tumors and 46 matched adjacent normal samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip.
Project description:Genome wide DNA methylation profiling of normal and primary oropharyngeal squamous cell carcinoma tissue samples, some infected with the human papilloma virus (HPV). The Illumina Infinium 27k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 27,000 CpGs in tissue samples. Samples included 46 oropharyngeal SCC primary tumors and 46 normal adjacent mucosal samples. For each tumor sample, HPV status (positivity based on both DNA and E6/E7 RNA) and p16 immunohistochemistry status is included.
Project description:Oropharyngeal squamous cell carcinoma (OPSCC) is diagnosed in 93,000 patients worldwide per year and 51,000 annual deaths can be attributed to this disease. OPSCCs are either human papillomavirus associated (HPV-positive) cancers or non-virally induced, primarily tobacco and alcohol associated (HPV-negative) cancers. MS analysis enabled the identification of naturally HLA-presented peptides in OPSCC tumor tissue. By comparative profiling against benign HLA ligandomic datasets, we demonstrated that tumor-associated peptides are HLA-presented on the cell surfaces of OPSCCs. The established warehouse of OPSCC-associated peptides can be used for downstream immunogenicity testing and peptide-based immunotherapy in (semi-) personalized strategies.
Project description:The global rise of HPV(+) oropharyngeal squamous cell carcinoma (OPSCC) has generated considerable interest underlying its etiology and management. Despite an overall decline in head and neck malignancies, the incidence in OPSCC has by contrast sharply risen, with HPV(+) subtypes now comprising 80% of all OPSCC.1,2 Relative to HPV(-) OPSCC, HPV(+) patients are more responsive to chemoradiation and harbor a 52% risk-of-death reduction.3 Despite this distinct outcome, treatment regimens remain the same for all OPSCC subtypes (smoking-driven and virus-driven), rather than an adaptive approach to what most consider distinct diseases. The short-term effects (e.g., mucositis, odynophagia) and long-term toxicities (e.g., xerostomia, dysphagia, ototoxicity) from treatment substantially affect quality of life, and rival the impact of the cancer itself. Recently published as well as ongoing trials are actively examining deintensification approaches2,4-9, with the goal of diminishing treatment sequelae for HPV(+) subtypes. While deintensification may decrease chemoradiation-related toxicities, it nonetheless may also undertreat a meaningful percentage of HPV(+) patients who may then recur. In examining national trials, 19% of HPV(+) patients had disease progression after therapy, with a two-year survival rate of 60%.10 Current methods to ascertain HPV status involve p16 staining. However, on comparison with gold standard E6/E7 expression by qPCR, p16 harbored a 15% false positivity rate11, suggesting limited utility as a sole biomarker for deintensification. Improved molecular stratification would greatly enhance the clinician’s ability to precisely tailor treatment while minimizing the risk of jeopardizing outcomes. One approach encompasses in-depth proteomic profiling of HPV(+) OPSCC to reveal distinct protein expression profiles and delineate clinically relevant upstream pathways. In turn, these proteomic differences may distinguish higher-risk disease (cases predisposed to recurrence that may benefit from treatment intensification) from lower-risk phenotypes (cases whose treatment response is sufficiently robust to warrant deintensification). Here, two HPV(+) OPSCC cohorts stratified by treatment response are compared via a hybrid data dependent acquisition/data independent acquisition (DDA/DIA) approach via mass spectrometry. We focused on detection of low-abundance proteins to highlight proteomic signatures that can be potentially exploited for treatment stratification.
Project description:DNA methylation analysis in oropharyngeal squamous carcinoma (OPSCC) samples and oropharyngeal non-cancerous mucosa samples. Infinium HumanMethylation450 BeadChip was used to obtain DNA methylation profiles across 485,577 CpG sites. Total samples included 89 OPSCC samples and 5 non-cancerous mucosa samples.