Recommendations for determining HPV status in patients with oropharyngeal cancers under TNM8 guidelines: a two-tier approach.

BACKGROUND: TNM8 staging for oropharyngeal squamous cell carcinomas (OPSCC) surrogates p16 immunohistochemistry for HPV testing. Patients with p16+ OPSCC may lack HPV aetiology. Here, we evaluate the suitability of TNM8 staging for guiding prognosis in such patients. METHODS: HPV status was ascertained using p16 immunohistochemistry and high-risk HPV RNA and DNA in situ hybridisation. Survival by stage in a cohort of OPSCC patients was evaluated using TNM7/TNM8 staging. Survival of p16+/HPV- patients was compared to p16 status. RESULTS: TNM8 staging was found to improve on TNM7 (log rank p = 0·0190 for TNM8 compared with p = 0·0530 for TNM7) in p16+ patients. Patients who tested p16+ but were HPV- (n = 20) had significantly reduced five-year survival (33%) compared to p16+ patients (77%) but not p16- patients (35%). Cancer stage was reduced in 95% of p16+/HPV- patients despite having a mortality rate twice (HR 2.66 [95% CI: 1.37-5.15]) that of p16+/HPV+ patients under new TNM8 staging criteria. CONCLUSION: Given the significantly poorer survival of p16+/HPV- OPSCCs, these data provide compelling evidence for use of an HPV-specific test for staging classification. This has particular relevance in light of potential treatment de-escalation that could expose these patients to inappropriately reduced treatment intensity as treatment algorithms evolve.

Evaluating the use of Floseal haemostatic matrix in the treatment of epistaxis: a prospective, control-matched longitudinal study.

Epistaxis is a common cause of emergency admissions in ENT. The use of Floseal haemostatic matrix in the treatment of epistaxis has been investigated in a number of studies in North America. We aimed to report a UK-based experience in the context of the current UK management paradigm. The study was designed as a prospective, unrandomised, control-matched longitudinal study. Cases were matched to controls in order to reduce the risk of bias. The overall treatment success rate for Floseal was 75 %, similar to the rates reported by studies based in North America. Nasal packing carried a success rate of 85 % and there was no statistically significant difference between the success rates of both treatments. Anecdotally Floseal can also be used successfully in thrombocyctopenic patients. There was a trend towards a shorter length of stay in the Floseal group, but this was not statistically significant. The 7-day readmission rate was 10 % for both the groups. This controlled study demonstrates that Floseal has a similar treatment success rate to nasal packing and that there may be a trend towards a shorter length of stay.

Assessment of Smell Function in Syndromic Craniosynostosis Patients.

Craniosynostosis is defined as premature fusion of the cranial suture lines and is part of a syndrome in 15% to 40% of the patients. There is limited literature available regarding these children's ability to smell. Most of them will undergo numerous surgical procedures, some of which may alter their sense of smell, potentially leading to significant social as well as safety implications. Ethical approval was obtained for this pilot study. Children with syndromic craniosynostosis were recruited and underwent anterior rhinoscopy, prior to performing a smell test utilizing the Sensonic pediatric Smell wheel. The results were compared to an age-matched control group. Eight children with syndromic craniosynostosis participated in the study. Of a possible total score of 11, their mean average score was 6.6 and the median was 6. In comparison, the mean average score for the control group was 7.5 and the median was 7. Although the study group was small, this pilot study demonstrates that children with syndromic craniosynostosis have a similar ability to identify smells to an age-matched cohort. Further research can now be undertaken to see whether or not midface advancement procedures affect these children's sense of smell.

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). Of these, 236 (68%) were HPV-negative, 110 (32%) positive. IGF-1R was detected in the cell membrane of 36% and cytoplasm of 92% of HNSCCs; in 64 cases with matched normal tonsillar epithelium, IGF-1R was overexpressed in the HNSCCs (P < 0.001). Overall survival (OS) and disease-specific survival (DSS) were reduced in patients whose tumors contained high membrane IGF-1R [OS: hazard ratio (HR) = 1.63, P = 0.006; DSS: HR = 1.63, P = 0.016], cytoplasmic IGF-1R (OS: HR = 1.58, P = 0.009; DSS: HR = 1.58, P = 0.024) and total IGF-1R (OS: HR = 2.02, P < 0.001; DSS: HR = 2.2, P < 0.001). High tumor IGF-1R showed significant association with high-tumor T-stage (P < 0.001) and HPV-negativity (P < 0.001), and was associated with shorter OS when considering patients with HPV-positive (P = 0.01) and negative (P = 0.006) tumors separately. IGF-1R was independently associated with survival in multivariate analysis including HPV, but not when lymphovascular invasion, perineural spread and T-stage were included. Of these factors, only IGF-1R can be manipulated; the association of IGF-1R with aggressive disease supports experimental incorporation of anti-IGF-1R agents into multimodality treatment programs for HPV-negative and high IGF-1R HPV-positive HNSCC.

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. Case notes were reviewed for demographic data, tumour stage, treatment, complications and outcomes. Eleven patients (all males) were identified. The mean age of the cohort was 58.2 years (range 37-78 years). The overall average follow-up period was 41.5 months (range 14 days-75 months). Of the 11 cases, 3 had completed stage 1 only. The most common complications following stage 1 procedure are related to the surgical neck wound (36% of cases). Of the remaining eight patients who completed the first two surgical stages, closure of tracheostomy stoma was possible in seven; all seven subsequently resumed a normal oral diet. All these patients have subsequently remained free of disease at latest follow-up. There were two cases of post-operative pneumonia and one case of radial forearm free-flap failure. In contrast, only one case of post-operative pneumonia was recorded following the stage 2 procedure. In total, three patients in this cohort were dead at follow-up. This technique has a role in the management of a select group of fit patients presenting with unilateral tumours of the glottis and who are otherwise destined for a total laryngectomy. Whilst the technique is complex, we have shown that its introduction is possible in a suitably specialised and motivated surgical unit.

An explanation for the worsened prognosis in some cancer patients of perioperative transfusion: the time-dependent release of biologically active growth factors from stored blood products.

Over 25 years ago Francis reported an association between blood transfusion and worsened cancer prognosis. Subsequently there has been much debate over whether there is in fact such an association, and if so, what is its underlying mechanism. Allogeneic blood transfusion is the most frequent allo-transplantation procedure performed on a routine basis with no prior HLA-typing. 50% of the recipients of unprocessed red cells and platelets become allo-immunised. It is our proposition that as result of normal physiological ageing and metabolic processes (with depletion of ATP and reduction of active membrane processes), there is leaching of biologically active substances from the cells into stored blood products. These leached bioactive substances have immuno-modulatory effects, which may in part explain the increased likelihood of postoperative sepsis and adult respiratory distress syndrome in transfusion recipients. They also promote cell growth and angiogenesis and may therefore have a direct effect on tumour growth. We provide evidence to support a possible hypothesis which could explain much of the conflicting clinical and experimental evidence.

Head and neck oncological ablation and reconstruction in the COVID-19 era - our experience to date.

The COVID-19 pandemic has caused unprecedented disruption to the routine operations of healthcare services across the world. As the potential duration of the pandemic remains uncertain, the need to develop strategies to continue urgent elective services has received increasing attention. A solution adopted in the Kent, Sussex and Surrey area of England has been to create COVID-19-protected cancer hubs. The Queen Victoria Hospital is the designated hub for head and neck cancer services in the area. We report on the evolution of the head and neck cancer care pathway and standard operating protocols put in place and how these have combined both national guidelines and local problem solving. It is hoped that our experience can help guide other centres as they re-establish head and neck cancer services during the ongoing pandemic.

Activation of cross-reactive mucosal T and B cell responses in human nasopharynx-associated lymphoid tissue in vitro by Modified Vaccinia Ankara-vectored influenza vaccines.

UNLABELLED: Recent efforts have been focused on the development of vaccines that could induce broad immunity against influenza virus, either through T cell responses to conserved internal antigens or B cell response to cross-reactive haemagglutinin (HA). We studied the capacity of Modified Vaccinia Ankara (MVA)-vectored influenza vaccines to induce cross-reactive immunity to influenza virus in human nasopharynx-associated lymphoid tissue (NALT) in vitro. Adenotonsillar cells were isolated and stimulated with MVA vaccines expressing either conserved nucleoprotein (NP) and matrix protein 1 (M1) (MVA-NP-M1) or pandemic H1N1 HA (MVA-pdmH1HA). The MVA vaccine uptake and expression, and T and B cell responses were analyzed. MVA-vectored vaccines were highly efficient infecting NALT and vaccine antigens were highly expressed by B cells. MVA-NP-M1 elicited T cell response with greater numbers of IFNγ-producing CD4+ T cells and tissue-resident memory T cells than controls. MVA-pdmH1HA induced cross-reactive anti-HA antibodies to a number of influenza subtypes, in an age-dependent manner. The cross-reactive antibodies include anti-avian H5N1 and mainly target HA2 domain. CONCLUSION: MVA vaccines are efficient in infecting NALT and the vaccine antigen is highly expressed by B cells. MVA vaccines expressing conserved influenza antigens induce cross-reactive T and B cell responses in human NALT in vitro, suggesting the potential as mucosal vaccines for broader immunity against influenza.

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. Human papillomavirus (HPV) status was determined by p16 immunohistochemistry and high-risk HPV DNA in situ hybridization. Survival analyses were evaluated using Kaplan-Meier statistics. RESULTS: Tumor subsites included tonsil (n = 94; 61.5%), tongue base (n = 38; 24.8%), and soft palate (n = 21; 13.7%), with the majority being American Joint Committee on Cancer (AJCC) stage III/IVa (n = 124; 81.0%) and HPV-positive (n = 101; 66.0%). Three-year overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were 84.5%, 91.7%, and 78.2%, respectively. HPV-positivity portended favorable oncologic outcomes. One-year gastrostomy tube (G-tube) dependency was 1.3%. CONCLUSION: To the best of our knowledge, this is the largest single-center TLM oropharyngeal SCC series to date. Our data suggest that TLM +/- postoperative radiotherapy (PORT) results in at least as good oncologic outcomes as chemoradiotherapy (CRT), while conferring swallowing function advantages. © 2016 Wiley Periodicals, Inc. Head Neck , 2016 © 2016 Wiley Periodicals, Inc. Head Neck 38:1263-1270, 2016.

HPV-Related Oropharynx Cancer in the United Kingdom: An Evolution in the Understanding of Disease Etiology.

A rising incidence of oropharyngeal squamous cell carcinoma (OPSCC) incidence has occurred throughout the developed world, where it has been attributed to an increasing impact of human papillomavirus (HPV) on disease etiology. This report presents the findings of a multicenter cross-sectional retrospective study aimed at determining the proportion of HPV-positive and HPV-negative OPSCC within the United Kingdom. Archival tumor tissue blocks from 1,602 patients previously diagnosed with OPSCC (2002-2011) were collated from 11 centers. HPV status was determined with three validated commercial tests to provide valid data for 1,474 cases in total. Corresponding national incidence data from the same decade were obtained from UK Cancer registries. The overall proportion of HPV+ OPSCC between 2002 and 2011 was 51.8% [95% confidence interval (CI), 49.3-54.4], and this remained unchanged throughout the decade [unadjusted RR = 1.00 (95% CI, 0.99-1.02)]. However, over the same period, the incidence of OPSCC in the broader UK population underwent a 2-fold increase [age-standardized rate 2002: 2.1 (95% CI, 1.9-2.2); 2011: 4.1 (95% CI, 4.0-4.3)]. Although the number of OPSCCs diagnosed within the United Kingdom from 2002 to 2011 nearly doubled, the proportion of HPV+ cases remained static at approximately 50%. Our results argue that the rapidly increasing incidence of OPSCC in the United Kingdom cannot be solely attributable to the influence of HPV. The parallel increase in HPV+ and HPV- cases we documented warrants further investigation, so that appropriate future prevention strategies for both types of disease can be implemented. Cancer Res; 76(22); 6598-606. ©2016 AACR.

Squamous cell carcinoma of the head and neck outside the oropharynx is rarely human papillomavirus related.

OBJECTIVES/HYPOTHESIS: The incidence of human papillomavirus (HPV)-driven disease beyond the oropharynx varies greatly in the reported literature. STUDY DESIGN: Case series. METHODS: Two hundred twenty-one samples were strictly classified to the subsites of oral cavity, larynx, or hypopharynx at the time of primary surgery. Formalin-fixed paraffin-embedded samples were subjected to a validated, tiered, diagnostic algorithm of p16 immunohistochemistry, high-risk HPV in situ hybridization, and quantitative polymerase chain reaction for HPV E6 DNA. An additional 60 oropharyngeal cases acted as an internal biological control. RESULTS: An incidence of 4% of HPV-driven cases was observed across the subsites outside the oropharynx compared to 70% of tumors confined within it. CONCLUSIONS: This is the first reporting of a broad range of nonoropharyngeal HPV rates using this validated diagnostic algorithm. It remains unclear whether patients with HPV-driven disease originating outside the oropharynx enjoy the same survival advantage apparent in those patients with oropharyngeal squamous cell carcinomas. LEVEL OF EVIDENCE: 4 Laryngoscope, 124:2739-2744, 2014.

Who should manage acute periorbital cellulitis in children?

INTRODUCTION: Periorbital cellulitis is inflammation of the eye anterior to the palpebral ligament. The sequeale may be life or vision threatening. There is no consensus on the optimal management strategies. METHODS: A two year retrospective case note analysis was performed on all hospital admissions to a tertiary children's hospital with the diagnosis. RESULTS: 226 notes were retrieved, 13 were excluded. The incidence of periorbital cellulitis was nearly 9 cases per month (8.875): the median length of stay was 2 days: all were treated with antibiotics. Only 7 children (3%) underwent surgical intervention. DISCUSSION: Due to potentially serious intracranial and orbital complications, authors have previously argued that all patients with periorbital cellulitis need daily otorhinolaryngology assessment. This current review showed a much larger incidence than in the published literature, with the majority being managed by the paediatricians and ophthalmologists. Escalation to otorhinolaryngology when first line treatment has failed is a more appropriate use of resources.