Biological agents in head and neck cancer

Survival of head and neck cancer (HNC) patients has not dramatically improved over the last 30 years, despite the advances in surgical techniques, chemotherapeutic agents and radiotherapy treatment planning and definition. Different studies in molecular biology of HNC have been carried out, providing useful results for clinical application. HNC usually includes malignant tumors arising from mucosa of the upper aerodigestive tract, from nasopharynx to larynx/trachea, while salivary gland and thyroid cancers are less frequently listed in this classification. In this review, we chose to provide a comprehensive review of the role of biological agents in head and neck subsites. Molecular characteristics and treatment-relevant signaling pathways will be briefly discussed along with the results of the more recent clinical studies that include biological agents.     

Elevated Src family kinase activity stabilizes E-cadherin-based junctions and collective movement of head and neck squamous cell carcinomas

EGF receptor (EGFR) overexpression is thought to drive head and neck carcinogenesis however clinical responses to EGFR-targeting agents have been modest and alternate targets are actively sought to improve results. Src family kinases (SFKs), reported to act downstream of EGFR are among the alternative targets for which increased expression or activity in epithelial tumors is commonly associated to the dissolution of E-cadherin-based junctions and acquisition of a mesenchymal-like phenotype. Robust expression of total and activated Src was observed in advanced stage head and neck tumors (N=60) and in head and neck squamous cell carcinoma lines. In cultured cancer cells Src co-localized with E-cadherin in cell-cell junctions and its phosphorylation on Y419 was both constitutive and independent of EGFR activation. Selective inhibition of SFKs with SU6656 delocalized E-cadherin and disrupted cellular junctions without affecting E-cadherin expression and this effect was phenocopied by knockdown of Src or Yes. These findings reveal an EGFR-independent role for SFKs in the maintenance of intercellular junctions, which likely contributes to the cohesive invasion E-cadherin-positive cells in advanced tumors. Further, they highlight the need for a deeper comprehension of molecular pathways that drive collective cell invasion, in absence of mesenchymal transition, in order to combat tumor spread.     

Testing for high‐risk HPV in cervical and tonsillar paraffin‐embedded tissue using a cartridge‐based assay

This study evaluates the suitability of Xpert HPV (Cepheid, Sunnyvale, CA, USA) test for cervical and tonsillar formalin‐fixed paraffin‐embedded (FFPE) tissue samples as compared to the tests currently used in diagnostics. Cervical biopsies and liquid cytology (LC) samples were collected from 48 women attending colposcopy. Biopsies were processed for histology and tested for hrHPV using Xpert HPV. LC samples were tested using Xpert and Hybrid Capture 2 (HC2; Qiagen, Hilden, Germany) tests. Also 29 archived tonsillar carcinoma samples were tested using Xpert, and the results were compared with histology and immunohistochemical p16INK4a (p16) staining. Among valid cervical LC samples 46.8% were hrHPV positive using Xpert test and 55.3% with HC2. The sensitivity of Xpert was 84.6% as compared to HC2, and overall test concordance was 91.5%. Test concordance between valid Xpert results from biopsies and LC samples was 84.6%. Among valid tonsillar samples 70.4% were hrHPV positive, and concordance of 96.3% was found between Xpert and p16 staining. To conclude, Xpert HPV test cartridge provides a convenient platform to test individual samples, including FFPE samples. Further studies are needed to establish whether test sensitivity is sufficient to reliably differentiate between hrHPV positive and hrHPV negative head and neck carcinomas.     

Current update on the diagnosis and management of head and neck soft tissue sarcomas

Head and neck soft tissue sarcomas are a group of rare heterogeneous tumours arising from embryonic mesoderm. They comprise <1% of all head and neck malignancies and 5–15% of all sarcomas with most head and neck sarcomas arising from soft tissues. Although rare, they are associated with both high recurrence and mortality rates. We review the current management of head and neck soft tissue sarcomas.     

Prognostic factors in head and neck mucoepidermoid carcinoma: experience at a single institution based on 64 consecutive patients over a 28-year period

Mucoepidermoid carcinoma (MEC) is the most common malignancy of the salivary glands. The clinical behaviour of MEC is largely unpredictable, ranging from indolent tumour growth to highly aggressive metastatic spread. The objective of this study was to determine the clinicopathological predictors of recurrence and survival in patients with head and neck MEC. The medical records of 64 patients who underwent surgical treatment for head and neck MEC between 1982 and 2010 were reviewed. The main outcome measures were disease-free survival (DFS) and overall survival (OS). Clinicopathological parameters evaluated were age, sex, anatomical subsite, histological grade, tumour stage, tumour size, adjuvant therapy, and nodal and margin status. For the entire cohort, the 5-year DFS was 82.8% and the 5-year OS was 67.2%. Histological grade and tumour subsite were statistically significant predictors of OS. Furthermore, tumour stage and nodal status were statistically significant predictors with respect to OS. Advanced tumour stage, high histological grade, submandibular/sublingual localization, and positive nodal status were independent predictors of the prognosis in patients with head and neck MEC. Further studies into the molecular biology of MEC are needed in order to provide new therapeutic strategies for patients with locally aggressive and highly metastatic carcinomas.