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

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

Intracranial management of perineural spread in the trigeminal nerve

Since the mid-1960s surgeons have attempted to cure intracranial perineural spread (PNS) of cutaneous malignancies. Untreated patients with trigeminal PNS die from brainstem invasion and leptomeningeal disease. It was understood that resection with clear margins was potentially curative, but early surgical attempts were unsuccessful. The prevailing wisdom considered that this surgery failed to improve the results achieved with radiation therapy alone and was associated with high morbidity. However, with improved imaging, surgical equipment, and better understanding of cavernous sinus (CS) anatomy and access, contemporary surgeons can improve outcomes for this disease. The aim of this paper is to describe a technique to access the interdural compartment of the CS and treat PNS of cutaneous squamous cell carcinoma (cSCC) in the intracranial trigeminal nerve and ganglion. It is based on the experience of the Queensland Skull Base Unit, Australia in managing PNS of cutaneous squamous cell carcinoma of the head and neck (cSCCHN)

Management of Squamous Cell Carcinoma Involving the Temporal Bone

Purpose of Review To examine contemporary management of squamous cell carcinoma (SCC) involving the temporal bone. Recent Findings The modified Pittsburgh criteria have gained acceptance by many institutions for staging, planning treatment and comparing outcomes. Often primary SCC as well as secondary cutaneous SCC involving the temporal bone can be managed in a similar fashion. Summary T1 tumours should undergo lateral temporal bone resection (LTBR) due to the higher risk of positive margins and recurrence rates with lesser surgical procedures. T2 tumours require LTBR and superficial parotidectomy. T3 and T4 tumours often require a subtotal resection of the temporal bone (STBR), parotidectomy and cutaneous soft tissues as an en bloc excision. Advanced lesions are associated with a diminished survival especially if margins are involved. Patient outcomes are improved by a combination of surgery and postoperative radiotherapy. Preoperative imaging with high resolution CT and MRI is useful, particularly if there is evidence of large nerve perineural spread and nodal disease

Surgical management of perineural spread of head and neck cancers

The surgical management of perineural spread of head and neck cancers has become an integral part in the contemporary treatment of this pathology. We now understand that tumour spreads within the epineurium and in a continuous fashion. We also can rely on the accuracy of magnetic resonance neurography in detecting and defining the extent of disease. With modern skull base techniques and a greater understanding of the anatomy in this region, specific operations can be designed to help eradicate disease. We review the current approaches and techniques used that enable us to better obtain tumour free margins and hence improve survival

An update on cellular microRNA expression in human papillomavirus-associated head and neck squamous cell carcinoma

Squamous cell carcinoma of mucosal sites in the head and neck (HNSCC) is the sixth most common cause of cancer worldwide, and despite advances in conventional management, it still has significant morbidity and mortality associated with both diagnosis and treatment. Advances in our understanding of the biological mechanisms underlying this disease have demonstrated a significant difference between human papillomavirus (HPV)-associated, HPV and tobacco associated, and HPV-negative disease. It remains important to further elucidate the biologic and genetic differences between HPV-associated and tobacco-associated disease, with the aim of earlier diagnosis through screening, and advances in management including the development of novel therapeutic agents. MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression, and have effects on almost every cellular function, and have potentially important applications to diagnosis, management and prognosis in HNSCC. Establishing a cellular miRNA expression profile for HPV-associated disease may therefore have important implications for the screening and treatment of this disease. This review summarises the current findings regarding miRNA expression in mucosal HNSCC, and focuses particularly on miRNA expression in HPV-associated tumours