Head and neck cancer

Squamous cell carcinomas of the head and neck (SCCHN), which arise from the mucosal surfaces of the upper aerodigestive tract, are the most common cancers of the head and neck region constituting the 6th most common cancer worldwide (~10,000 cases per annum in the UK).(1) Contemporary curative treatments include surgery, radiotherapy +/- cisplatin or combinations thereof, although anti-EGFR drugs and immunotherapeutic agents are licenced for specific clinical indications including the recurrent metastatic setting.(2,3) SCCHN exhibits variable responses to conventional treatment. Clinical response rates correlate with survival and are inversely related to primary tumour size, presence and volume of metastatic disease in the cervical lymph nodes and pathological evidence of tumour spread through the lymph node capsule (Extracapsular spread - ECS). Variability in treatment responsiveness has increased over recent decades with the emergence of a new discrete disease entity – Human papillomavirus associated oropharyngeal squamous cell carcinoma (HPV+ OPC) the incidence of which has doubled in the UK, US and Northern Europe

Sinonasal Cancers, incl. Olfactory Neuroblastoma, Paediatric Head and Neck Tumours & Salivary Gland Cancers. Tumours in this group are extremely rare and very little, if anything, is known about their molecular biology. The 100k genome project provides a perfect opportunity to start to fill this void by sequencing a small series of these tumours. No such datasets currently exist in the world to date.

Olfactory neuroblastoma is a rare, aggressive tumour of the sinonasal region originating from olfactory neuroepithelium. Its incidence is estimated to be 0.51/1,000,000 population per year and, its incidence peaks in the second and fifth decades of life.(4) Its aetiology is unknown. An infectious cause has been suggested because the tumour contains viral particles,(5,6) but inadequate data are available to either confirm or refute a viral cause. Our proposed WGS analysis of olfactory neuroblastoma will shed light on this; non-human reads will be mapped to both known or predicted RNA and DNA viruses to detect novel viral contributors. Paediatric patients appear to have a more aggressive presentation than adults with a larger proportion of cases with advanced disease.

Salivary gland tumours represent 1—4% of all human neoplasms and fewer than 5% occur in children and adolescents. In adults, 15—25% of all epithelial salivary gland tumours are malignant, however, this increase to 50—60% in children and adolescents.(7) Variations in protein expression and genetic alterations in tumoural cells has been shown in some paediatric salivary gland tumors, but further studies are necessary to evaluate their clinical significance

Sinonasal Cancers, incl. Olfactory Neuroblastoma, Paediatric Head and Neck Tumours & Salivary Gland Cancers. Tumours in this group are extremely rare and very little, if anything, is known about their molecular biology. The 100k genome project provides a perfect opportunity to start to fill this void by sequencing a small series of these tumours. No such datasets currently exist in the world to date.

Olfactory neuroblastoma is a rare, aggressive tumour of the sinonasal region originating from olfactory neuroepithelium. Its incidence is estimated to be 0.51/1,000,000 population per year and, its incidence peaks in the second and fifth decades of life.(4) Its aetiology is unknown. An infectious cause has been suggested because the tumour contains viral particles,(5,6) but inadequate data are available to either confirm or refute a viral cause. Our proposed WGS analysis of olfactory neuroblastoma will shed light on this; non-human reads will be mapped to both known or predicted RNA and DNA viruses to detect novel viral contributors. Paediatric patients appear to have a more aggressive presentation than adults with a larger proportion of cases with advanced disease.

Since the early 1990s, thyroid cancer incidence rates have increased by almost three-quarters in the UK. This trend is set to continue with a current incidence of 11 cases per 100,000 people which equates to >3000 cases per year in England.(8) Thyroid cancer is the most frequent endocrine cancer and contributes to 1-2% of all malignancies diagnosed each year. Thyroid nodules have a reported prevalence varying from 3% to 68% (depending on the evaluated population and the applied screening method), while carcinoma occur in less than 1% of nodules.(7) Most thyroid carcinomas originate from follicular epithelial cells and include well-differentiated papillary thyroid carcinomas (~80% of all thyroid malignancies) and follicular thyroid carcinomas (~15% of thyroid malignancies). Moreover, anaplastic (undifferentiated) carcinoma (1-2% of thyroid cancers) is the most aggressive thyroid malignancy to develop from epithelial cells. Medullary thyroid carcinoma in contrast, is derived from parafollicular C-cells and has neuroendocrine features (3-5% of thyroid cancers). Most thyroid tumours are diagnosed initially by morphological assessment of cells procured following fine needle aspiration cytology (FNAC) of a thyroid nodule. The resulting classification (Thy1-5) informs selection of a treatment and prognosis.(9) However, the final diagnosis is based on histopathological examination of thyroid tissue after surgical removal. It is often the case that cytological and histological patterns are ambiguous and definitive classification is problematic. Certain thyroid tumours can be challenging to diagnose even on histologic specimens due to a follicular growth pattern that includes a broad range of lesions that are difficult to distinguish. These lesions include benign follicular thyroid adenomas, hyperplastic nodules, follicular carcinomas, medullary thyroid carcinomas and follicular variant of papillary thyroid carcinomas.16 Papillary thyroid carcinoma is now the most over diagnosed thyroid lesion, since it shares multiple features with benign lesions (e.g. Hashimoto's thyroiditis, nodular hyperplasia) as well as with other malignant lesions (e.g. follicular / medullary carcinoma. Hence, additional tests are essential to classify thyroid tumours that exhibit non-standard morphological patterns. Molecular diagnostic tools have only a minimal role in the routine assessment of thyroid cancers. At present, no specific molecular biomarkers are used in current clinical practice which would allow discrimination from other differentiated thyroid cancers, although in most cases the expression of calcitonin could reliably differentiate medullary from follicular tumours. Although some possible biomarkers were proposed to confirm the diagnosis of PTC, they are not routinely used in clinical practice.(10)