Differential Regulation of the STING Pathway in Human Papillomavirus-Positive and -Negative Head and Neck Cancers.

Unlabelled: Squamous cell carcinomas, which arise from the cells that line the mucosal surfaces of the head and neck, represent the most common type of head and neck cancers (HNSCC). Human papillomavirus (HPV) infection has been strongly associated with the development of oropharyngeal cancers, which are cancers that occur in the back of the throat, including the tonsils and base of the tongue. HNSCCs with and without HPV infection have distinct pathology, with HPV-positive patients having higher levels of immune infiltration, activation in the tumor microenvironment and better response to radiation and chemotherapy.

Developing and Validating a Multivariable Prognostic-Predictive Classifier for Treatment Escalation of Oropharyngeal Squamous Cell Carcinoma: The PREDICTR-OPC Study.

Purpose: While there are several prognostic classifiers, to date, there are no validated predictive models that inform treatment selection for oropharyngeal squamous cell carcinoma (OPSCC).Our aim was to develop clinical and/or biomarker predictive models for patient outcome and treatment escalation for OPSCC.

Experimental Design: We retrospectively collated clinical data and samples from a consecutive cohort of OPSCC cases treated with curative intent at ten secondary care centers in United Kingdom and Poland between 1999 and 2012.

Patient preference for commonly-used, head and neck cancer-specific quality of life questionnaires in the follow-up setting (Determin): A multi-centre randomised controlled trial and mixed methods study.

Background: Quality of life (QoL) assessment forms an integral part of modern cancer care and research. The aim of this study is to determine patients' preferences and willingness to complete commonly used head-and-neck cancer (HNC) QoL questionnaires (QLQs) in routine follow-up clinics.

Methods: This is a randomised control trial of 583 subjects from 17 centres during follow-up after treatment for oral, oropharyngeal or laryngeal cancer.

Metabolic Plasticity and Combinatorial Radiosensitisation Strategies in Human Papillomavirus-Positive Squamous Cell Carcinoma of the Head and Neck Cell Lines.

Background: A major objective in the management of human papillomavirus (HPV)-positive squamous cell carcinoma of the head and neck (SCCHN) is to reduce long-term functional ramifications while maintaining oncological outcomes. This study examined the metabolic profile of HPV-positive SCCHN and the potential role of anti-metabolic therapeutics to achieve radiosensitisation as a potential means to de-escalate radiation therapy.

Methods: Three established HPV-positive SCCHN cell lines were studied (UM-SCC-104, UPCI:SCC154, and VU-SCC-147), together with a typical mutant HPV-negative SCCHN cell line (UM-SCC-81B) for comparison.

Elective management of regional nodal basins in cutaneous squamous cell carcinoma of the head and neck: Controversies and contemporary perspectives.

Non-melanoma skin cancer (NMSC) is among the most common cancers worldwide, with an incidence that continues to rise. Although cutaneous squamous cell carcinoma (cSCC) constitutes only approximately 20% of such cases, it represents the most common cause of NMSC mortality, owing largely to the propensity for development of regional lymph node metastases (LNM), which, when present, carry a dismal prognosis. Whilst overall rates of LNM are low, there are a number of patient and tumour factors that likely confer considerably higher risks, which has led several investigators to propose more proactive elective management of regional nodal basins in selected high-risk cases.

STINGing Viral Tumors: What We Know from Head and Neck Cancers.

It has now become increasingly clear that viruses, which may not be directly oncogenic, can affect the biology of tumors as well as immune behavior against tumors. This has led to a fundamental question: Should tumors associated with viral infection be considered distinct from those without? Typically, viruses activate the host innate immune responses by stimulating pathogen recognition receptors and DNA-sensing pathways, including the stimulator of interferon genes (STING) pathway. However, regulation of the STING pathway in a virus-associated tumor microenvironment is poorly understood.

Transoral laser microsurgery and radiotherapy for oropharyngeal squamous cell carcinoma: Equitable survival and enhanced function compared with contemporary standards of care.

Introduction: We describe the 5-year oncological and functional outcomes of transoral laser microsurgery, neck dissection (TLM + ND) and adjuvant radiotherapy (PORT) used to treat patients with oropharyngeal carcinoma. The effectiveness of external carotid artery (ECA) ligation in reducing post-operative bleeding, and fibrin glue following ND in reducing wound drainage and length of hospital stay is reported.

Materials And Methods: This retrospective case review of consecutive patients undergoing TLM between 2006 and 2017 used the Kaplan-Meier Estimator and Log-Rank Test for univariate, time-to-event analyses, and Cox-Proportionate Hazard modelling for multivariate analysis.

Outcomes and prognosticators in regionally recurrent cutaneous squamous cell carcinoma of the head and neck.

Introduction: Data regarding regionally metastatic cutaneous squamous cell carcinoma of the head and neck (cSCCHN) is limited and derived almost exclusively from Australian and United States (US) institutions. We report the first United Kingdom perspective, with the aims of benchmarking survival outcomes and identifying clinically relevant prognosticators.

Materials And Methods: Ninety-one patients with regionally recurrent cSCCHN treated with curative intent over a ten-year period (2009-2018) were studied retrospectively.

TP53 mutations in head and neck cancer cells determine the Warburg phenotypic switch creating metabolic vulnerabilities and therapeutic opportunities for stratified therapies.

Patients with mutated TP53 have been identified as having comparatively poor outcomes compared to those retaining wild-type p53 in many cancers, including squamous cell carcinomas of the head and neck (SCCHN). We have examined the role of p53 in regulation of metabolism in SCCHN cells and find that loss of p53 function determines the Warburg effect in these cells. Moreover, this metabolic adaptation to loss of p53 function creates an Achilles' heel for tumour cells that can be exploited for potential therapeutic benefit.

Metabolic signature of squamous cell carcinoma of the head and neck: Consequences of TP53 mutation and therapeutic perspectives.

There is a pressing need to identify ways of sensitising squamous cell carcinomas of the head and neck (SCCHN) to the effects of current treatments, both from oncological and functional perspectives. Alteration to cellular metabolism is now widely considered a hallmark of the cancer phenotype; presents a potentially attractive therapeutic target in this regard; and as such has received renewed research interest in recent years. However, whilst metabolic disruption may occur to some degree in all tumours, there is undoubtedly heterogeneity and detailed study of individual tumour types is paramount if effective therapeutic strategies targeting metabolism are to be developed and effectively deployed.

Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European Multicentre Study (OroGrams).

Background: The proxy marker for human papillomavirus (HPV), p16, is included in the new AJCC 8th/UICC 8th staging system, but due to incongruence between p16 status and HPV infection, single biomarker evaluation could lead to misallocation of patients. We established nomograms for overall survival (OS) and progression-free survival (PFS) in patients with oropharyngeal squamous cell carcinoma (OPSCC) and known HPV-DNA and p16 status, and validated the models in cohorts from high- and low-prevalent HPV countries.

Methods: Consecutive OPSCC patients treated in Denmark, 2000-2014 formed the development cohort.

Transoral laser microsurgery for oropharyngeal squamous cell carcinoma: A paradigm shift in therapeutic approach.

Background: The contemporary treatment of oropharyngeal squamous cell carcinoma (SCC) is an area of debate. We report outcomes of a minimally invasive approach involving transoral laser microsurgery (TLM).

Methods: A consecutive series of patients (n = 153) undergoing primary TLM for oropharyngeal SCC from 2006 to 2013 was studied.

PATHOS: a phase II/III trial of risk-stratified, reduced intensity adjuvant treatment in patients undergoing transoral surgery for Human papillomavirus (HPV) positive oropharyngeal cancer.

Background: Human papillomavirus-positive oropharyngeal squamous cell carcinoma is increasing in incidence worldwide. Current treatments are associated with high survival rates but often result in significant long-term toxicities. In particular, long-term dysphagia has a negative impact on patient quality of life and health.

IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer.

Head and neck squamous cell carcinomas (HNSCC) are treated with surgery, radiotherapy and cisplatin-based chemotherapy, but survival from locally-advanced disease remains poor, particularly in patients whose tumors are negative for Human papillomavirus (HPV). Type 1 IGF receptor (IGF-1R) is known to promote tumorigenesis and resistance to cancer therapeutics. Here, we assessed IGF-1R immunohistochemistry on tissue microarrays containing 852 cores from 346 HNSCC patients with primary tumors in the oropharynx (n = 231), larynx (85), hypopharynx (28), oral cavity (2).

Relative expression of vascular endothelial growth factor isoforms in squamous cell carcinoma of the head and neck.

Background: Alternative splicing of the vascular endothelial growth factor (VEGF) gene results in a family of antiangiogenic isoforms (VEGFxxx b), not yet investigated in squamous cell carcinoma of the head and neck (SCCHN). We examined, therefore, the prognostic value of the relative expression of VEGF isoforms in SCCHN.

Methods: A tissue microarray comprising 187 SCCHNs was studied by immunohistochemistry with total VEGF (panVEGF) and VEGFxxx b-specific antibodies, and scored by 2 assessors for intensity and proportion.

Extended vertical hemilaryngectomy and reconstruction with a neovascularised tracheal autograft for advanced unilateral laryngeal tumours: a learning curve.

Extended vertical hemilaryngectomy and reconstruction with a neovascularised tracheal autograft is a two-stage procedure for advanced unilateral tumours of the larynx. The purpose of this study was to review our early experience of this technique by reporting our clinical outcomes and highlighting some key learning points. Patients were identified from the Liverpool Head and Neck Cancer electronic database.

Evaluation of human papilloma virus diagnostic testing in oropharyngeal squamous cell carcinoma: sensitivity, specificity, and prognostic discrimination.

Purpose: Human papillomavirus-16 (HPV16) is the causative agent in a biologically distinct subset of oropharyngeal squamous cell carcinoma (OPSCC) with highly favorable prognosis. In clinical trials, HPV16 status is an essential inclusion or stratification parameter, highlighting the importance of accurate testing.

Experimental Design: Fixed and fresh-frozen tissue from 108 OPSCC cases were subject to eight possible assay/assay combinations: p16 immunohistochemistry (p16 IHC); in situ hybridization for high-risk HPV (HR HPV ISH); quantitative PCR (qPCR) for both viral E6 RNA (RNA qPCR) and DNA (DNA qPCR); and combinations of the above.

Loss of MTBP expression is associated with reduced survival in a biomarker-defined subset of patients with squamous cell carcinoma of the head and neck.

Background: Recent genetic studies have implicated p53 mutation as a significant risk factor for therapeutic failure in squamous cell carcinoma of the head and neck (SCCHN). However, in a recent meta-analysis in the literature of p53 from major anatomical subsites (larynx, oral cavity, oropharynx/hypopharynx), associations between patient survival and p53 status were ambiguous.

Methods: The authors examined a cohort of SCCHNs using a previously developed biomarker combination that likely predicts p53 status based on p53/MDM2 expression levels determined by immunohistochemistry (IHC).

A systematic review of p53 as a prognostic factor of survival in squamous cell carcinoma of the four main anatomical subsites of the head and neck.

Objectives: To summarize existing evidence about whether the presence of mutant or upregulated p53 is a prognostic factor for patients presenting with squamous cell carcinoma arising from the larynx, oropharynx, hypopharynx, or oral cavity.

Method: Relevant articles were identified using strict criteria for systematic searches. Associations between mutant or upregulated p53 versus wild-type or low/undetectable p53 in relation to overall survival and DFS were summarized by extracting or deriving hazard ratio (HR) estimates.

Survival of patients with neck recurrence following radical neck dissection: utility of a second neck dissection?

Treatment of neck recurrence following radical neck dissection is extremely difficult. Retrospective review of 699 radical neck dissections was performed. Recurrence rates, host, tumor, treatment factors, and survival were analyzed.

Treatment of squamous cell carcinoma of the tongue base: irradiation, surgery, or palliation?

Objectives: Squamous cell carcinoma of the tongue base has a poor prognosis, and treatment is accompanied by a number of major problems. In view of this, it is important to recognize which patients will benefit from treatment with curative intent and which treatment method to use.

Methods: One hundred sixty-five patients with squamous cell carcinoma of the tongue base were identified on our database.

Metastatic testicular seminoma--a case report.

We present the case of a 42-year-old male who presented with a hot, tender swelling in the left supraclavicular fossa. He was pyrexial on presentation with a mildly elevated leucocyte count of 12.4x10(9)/l.