Project Details
Description
Even for early stage (I/II) oral cavity squamous cell carcinoma (OSCC), 5-year survival rates remain poor at between 55-60% and loco-regional recurrence remains a major issue.1,2 No biomarkers currently exist to accurately predict recurrence or survival in this disease. Liquid biopsies have been shown to both detect and monitor malignant lung tumours and can reflect tumour heterogeneity.3 As saliva bathes the whole oral cavity, it may be more representative of the exposed field, in comparison to non-representative tissue biopsies. Saliva is also a source of oral epithelial cells and lymphocytes, so may contain both tumour-related and normal tissue.
Several studies have attempted to investigate methylation biomarkers for OSCC but all have failed to demonstrate prognostic ability. The limitations of previous studies include poorly phenotyped, small cohorts which often combine multiple head and neck cancer subsites, alongside the use of targeted arrays.4-13 Most recently, the high-Risk Epigenetic And clinicopathologic Score for Oral caNcer (REASON) score has been developed by Viet et al.14 which claims to accurately predict 5-year survival (c-index= 0.915). This combines a methylation score with clinicopathological data, but was developed using only 58 tumour samples from six different sites and mostly (70%) stage II cancer, with data taken from The Cancer Genome Atlas (TGCA). Therefore, validation in a larger cohort is required.14
The Head and Neck 5000 study provides a unique collection of saliva samples taken from n= 400 OSCC participants, which may be used for DNA methylation profiling. The protocol collected up to four 1mL aliquots, with 3-year survival data for this cohort ranging between 40-50%.
We hypothesise that:
• Saliva can be used as a prognostic biomarker in OSCC.
• DNA methylation signatures from saliva are predictive of OSCC recurrence and survival.
The aims and objectives of this study are therefore:
1) To identify novel DNA methylation signatures in saliva related to OSCC recurrence and survival outcomes (disease-specific and overall survival).
2) To develop models of OSCC recurrence and survival using DNA methylation in saliva and evaluate their clinical utility to identify patients who would benefit from closer observation or more aggressive treatment (e.g., elective neck dissection).
3) To investigate the causal relationship between DNA methylation and OSCC risk factors/ exposures, stage, and outcomes to potentially identify mechanisms amenable to intervention (e.g., druggable targets).
Several studies have attempted to investigate methylation biomarkers for OSCC but all have failed to demonstrate prognostic ability. The limitations of previous studies include poorly phenotyped, small cohorts which often combine multiple head and neck cancer subsites, alongside the use of targeted arrays.4-13 Most recently, the high-Risk Epigenetic And clinicopathologic Score for Oral caNcer (REASON) score has been developed by Viet et al.14 which claims to accurately predict 5-year survival (c-index= 0.915). This combines a methylation score with clinicopathological data, but was developed using only 58 tumour samples from six different sites and mostly (70%) stage II cancer, with data taken from The Cancer Genome Atlas (TGCA). Therefore, validation in a larger cohort is required.14
The Head and Neck 5000 study provides a unique collection of saliva samples taken from n= 400 OSCC participants, which may be used for DNA methylation profiling. The protocol collected up to four 1mL aliquots, with 3-year survival data for this cohort ranging between 40-50%.
We hypothesise that:
• Saliva can be used as a prognostic biomarker in OSCC.
• DNA methylation signatures from saliva are predictive of OSCC recurrence and survival.
The aims and objectives of this study are therefore:
1) To identify novel DNA methylation signatures in saliva related to OSCC recurrence and survival outcomes (disease-specific and overall survival).
2) To develop models of OSCC recurrence and survival using DNA methylation in saliva and evaluate their clinical utility to identify patients who would benefit from closer observation or more aggressive treatment (e.g., elective neck dissection).
3) To investigate the causal relationship between DNA methylation and OSCC risk factors/ exposures, stage, and outcomes to potentially identify mechanisms amenable to intervention (e.g., druggable targets).
| Status | Active |
|---|---|
| Effective start/end date | 30/06/24 → 1/09/25 |
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