Genome stability pathways in head and neck cancers

Genomic instability underlies the transformation of host cells toward malignancy, promotes development of invasion and metastasis and shapes the response of established cancer to treatment. In this review, we discuss recent advances in our understanding of genomic stability in squamous cell carcinoma of the head and neck (HNSCC), with an emphasis on DNA repair pathways. HNSCC is characterized by distinct profiles in genome stability between similarly staged cancers that are reflected in risk, treatment response and outcomes. Defective DNA repair generates chromosomal derangement that can cause subsequent alterations in gene expression, and is a hallmark of progression toward carcinoma. Variable functionality of an increasing spectrum of repair gene polymorphisms is associated with increased cancer risk, while aetiological factors such as human papillomavirus, tobacco and alcohol induce significantly different behaviour in induced malignancy, underpinned by differences in genomic stability. Targeted inhibition of signalling receptors has proven to be a clinically-validated therapy, and protein expression of other DNA repair and signalling molecules associated with cancer behaviour could potentially provide a more refined clinical model for prognosis and treatment prediction. Development and expansion of current genomic stability models is furthering our understanding of HNSCC pathophysiology and uncovering new, promising treatment strategies

The relationship between physical impairments, quality of life and disability of the neck and upper limb in patients following neck dissection

The purpose of this study was to examine the relationship between physical impairments, quality of life and disability in patients following neck dissection, with consideration of patient and clinical characteristics.Cross-sectional study of patient

Development of an in vivo murine model of perineural invasion and spread of cutaneous squamous cell carcinoma of the head and neck

IntroductionCutaneous squamous cell carcinoma of the head and neck (cSCCHN) can metastasize by invading nerves and spread toward the central nervous system. This metastatic process is called perineural invasion (PNI) and spread (PNS). An in vivo sciatic nerve mouse model is used for cSCCHN PNI/PNS. Here we describe a complementary whisker pad model which allows for molecular studies investigating drivers of PNI/PNS in the head and neck environment.MethodsA431 cells were injected into the whisker pads of BALB/c Foxn1nu and NSG-A2 mice. Tumor progression was monitored by bioluminescence imaging and primary tumor resection was performed. PNI was detected by H&E and IHC. Tumor growth and PNI were assessed with inducible ablation of LOXL2.ResultsThe rate of PNI development in mice was 10%-28.6%. Tumors exhibited PNI/PNS reminiscent of the morphology seen in the human disease. Our model’s utility was demonstrated with inducible ablation of LOXL2 reducing primary tumor growth and PNI.DiscussionThis model consists in a feasible way to test molecular characteristics and potential therapies, offers to close a gap in the described in vivo methods for PNI/PNS of cSCCHN and has uses in concert with the established sciatic nerve model

Outcomes following surgery and post-operative radiotherapy for perineural spread of head and neck cutaneous squamous cell carcinoma

Background Queensland, Australia, has the highest rates of cutaneous squamous cell carcinoma (SCC). Perineural invasion (PNI) is associated with reduced local control and survival. Methods A retrospective review of a prospective database of patients with clinical PNI from cutaneous SCC of the head and neck (SCCHN) treated with surgery and postoperative radiotherapy (PORT) between 2000 and 2011 and a minimum of 24 months follow-up. Patients were excluded if immunosuppressed, had non-SCC histology, or were treated palliatively. Results Fifty patients (mean age, 60 years) with median follow-up of 50 months were included in this study. A total of 54.8% of known primary tumors had incidental PNI. Ten percent had nodal disease at presentation. MRI neurogram was positive in 95.8%. Recurrence-free survival (RFS) at 5-years was 62%. Five-year disease-specific survival (DSS) and overall survival (OS) were 75% and 64%, respectively. There were no perioperative deaths. Conclusion This report demonstrates that long-term survival is achievable in patients with clinical PNI from cutaneous SCCHN after surgery and PORT

Populism in world politics: a comparative cross-regional perspective

Populism has become more salient in multiple regions in the world, in developed as well as developing countries. Today it is largely a reaction to social dislocations tied to processes of neoliberal globalisation. As a concept, populism has had a long and contentious history. We suggest that populism has been on the rise alongside new imaginings of what constitutes the ‘people’ and ‘elites’, as the meanings attached to these labels are continually reshaped in conjunction with new social conflicts. These conflicts are intensifying across the globe together with new kinds of social marginalisation, precarious existence and disenchantment with the broken promises of liberal modernity. The article introduces a special issue on Populism in World Politics that seeks to understand general processes involved in the emergence of populist politics along with specific circumstances that affect how it is expressed in terms of identity politics, political strategies and shifting social bases

An overview of head and neck malignancy with perineural spread

This article provides an overview of perineural spread of head and neck malignancy. It defines the problem and explores some of the unique features, which occur with this pathology. The expectation is for a better understanding of this extraordinary disease, hopefully leading to earlier diagnosis and for a more consistent reporting of results. It summarizes the topics to be covered in this special edition, which should leave the reader with a fairly complete understanding of the contemporary issues of perineural spread

Petro-occipital transsigmoid approach

Tumors of the jugular foramen are rare and often benign. The surgical management of these conditions is often associated with considerable post operative morbidity. Complications include injury to the lower cranial nerves causing dysphagia and dysphonia, facial nerve paresis and loss of hearing. The POTS approach takes the vector of dissection from a lateral trajectory to a posterio-lateral trajectory. In the setting of the more posteriorly placed jugular foramen schwannomas this allows for resection and offers the opportunity for preservation of auditory and facial function

Vestibular schwannomas: An understanding of growth should influence management decisions

Background: Treatments for vestibular schwannomas include surgical removal and radiotherapy. Observation is a reasonable alternative, given the slow growth of these tumors. The goal of this study was to determine the 5-year no-growth rate in patients managed initially by observation in attempts to define indications for treatment