Head and neck cancer incidence is rising but the sociodemographic profile is unchanging: a population epidemiological study (2001-2020).

Background: Increasing incidence of head and neck cancers (HNCs), driven by rising rates of oropharynx cancer (OPC), has been recorded around the world. This study examined trends in HNC and subsites (oral cavity, oropharynx, and larynx cancers) in Scotland focusing on assessing whether the sociodemographic profile has changed over the past 20 years. Methods: Scottish Cancer Registry data (2001-2020) including European Age Standardised Rates of HNC and subsites were analysed in multivariate Poisson regression by age, sex, area-based socioeconomic status, and year of diagnosis (with interaction tests). Results: Overall HNC and oral cavity cancer (OCC) incidence remained relatively stable. OPC incidence rates increased by 78%, while larynx cancer incidence declined by 27%. Over time, there were marginal shifts to a slightly older age profile for HNC (p = 0.001) and OCC (p = 0.001), but no changes in OPC (p = 0.86) and larynx cancer (p = 0.29). No shift in the sex profile of HNC was observed except for minor increases in female OCC rates (p = 0.001), and the socioeconomic distribution remained unchanged across all HNC subsites. Conclusions: There have been no significant changes in the sociodemographic profile of HNC in Scotland over the last 20 years, despite the changing trends in HNCs with dramatically increasing incidence rates in OPC and reducing larynx cancer. This information can be used to target or stratify HNC prevention and control.

Hydrogel-chitosan and polylactic acid-polycaprolactone bioengineered scaffolds for reconstruction of mandibular defects: a preclinical in vivo study with assessment of translationally relevant aspects.

Background: Reconstruction of mandibular bone defects is a surgical challenge, and microvascular reconstruction is the current gold standard. The field of tissue bioengineering has been providing an increasing number of alternative strategies for bone reconstruction. Methods: In this preclinical study, the performance of two bioengineered scaffolds, a hydrogel made of polyethylene glycol-chitosan (HyCh) and a hybrid core-shell combination of poly (L-lactic acid)/poly ( ε -caprolactone) and HyCh (PLA-PCL-HyCh), seeded with different concentrations of human mesenchymal stromal cells (hMSCs), has been explored in non-critical size mandibular defects in a rabbit model. The bone regenerative properties of the bioengineered scaffolds were analyzed by in vivo radiological examinations and ex vivo radiological, histomorphological, and immunohistochemical analyses. Results: The relative density increase (RDI) was significantly more pronounced in defects where a scaffold was placed, particularly if seeded with hMSCs. The immunohistochemical profile showed significantly higher expression of both VEGF-A and osteopontin in defects reconstructed with scaffolds. Native microarchitectural characteristics were not demonstrated in any experimental group. Conclusion: Herein, we demonstrate that bone regeneration can be boosted by scaffold- and seeded scaffold-reconstruction, achieving, respectively, 50% and 70% restoration of presurgical bone density in 120 days, compared to 40% restoration seen in spontaneous regeneration. Although optimization of the regenerative performance is needed, these results will help to establish a baseline reference for future experiments.

Early provision of clinical information with an 'opt in' approach improves patient experience in tonsillectomy referrals.

Patients referred by their general practitioner (GP) with a definite diagnosis, for example, recurrent sore throat for consideration of tonsillectomy in adults, may wait for months without receiving any further clinical information from the hospital until their outpatient consultation. Prompt provision of condition-specific information after referral has received little attention despite considerable potential to enhance patients' understanding, thereby relieving uncertainty and anxiety, and facilitating shared decision-making.This study aimed to report the experience of patients with recurrent tonsillitis who had been sent a booklet outlining the benefits and risks of tonsillectomy immediately after GP referral.Greater Glasgow and Clyde Health Board received 218 referrals of patients aged 16-40 to discuss tonsillectomy between January and August 2022. Every patient was sent a 16-page booklet by post and given the choice to opt in for a consultation.165 (76%) patients opted in, and 53 (24%) did not. Feedback was obtained from 143 patients (66%) from both groups. 99% found the information booklet easy to understand, 97% would recommend it to a friend with recurrent tonsillitis, 93% felt their questions had been answered and 92% believed it helped them to decide whether to proceed with tonsillectomy. Socioeconomic deprivation did not influence the outcome.In conclusion, most patients found provision of clinical information immediately after vetting of the referral to be beneficial, irrespective of whether they opted in for a consultation. This concept has broad applicability across all specialties, and the principles can be readily adopted and adapted by clinicians and managers in local units.

Carbon footprint of tonsillectomy.

BACKGROUND AND PURPOSE: Healthcare is responsible for 5.4% of greenhouse gas emissions in the UK. Emissions in surgery is a relatively unexplored area; in particular, this hasn't yet been looked at as a whole in ENT in the UK. The purpose of the study was to quantify the amount of greenhouse gas (GHG) emission from a tonsillectomy and assess the proportion of each source's contribution. METHODS: Operational data from tonsillectomies performed at a large university teaching hospital in the UK were gathered and converted to global warming potential using established conversion factors and data from existing healthcare-focused carbon footprint studies. The domains considered were waste, pharmaceuticals, surgical instrument decontamination, transportation, consumables use and utilities. This study used a process-based carbon footprint approach based on the "Greenhouse Gas Protocol: Product Life Cycle Accounting and Reporting Standard". MAIN FINDINGS: The carbon footprint of a typical case was 41 kgCO2e which is equivalent to driving a car for approximately 150 miles. Consumables were responsible for 17% of this; 14% came from transport, 5.4% from decontamination, 4.8% from pharmaceuticals and 4% from waste. However, the largest GHG was from utilities, of which heating, ventilation and air conditioning was the overwhelming contributor. CONCLUSIONS: While the largest sources of GHG emissions require hospital-wide initiatives, there are aspects of consumables and waste streams we can improve on in ENT surgery. These include the use of disposable vs reusable instruments as well as increased availability and use of recycling waste streams in theatres. Additionally, this study provides a template that can be applied to other ENT procedures.

Understanding the Role of Biofilms in Acute Recurrent Tonsillitis through 3D Bioprinting of a Novel Gelatin-PEGDA Hydrogel.

Acute recurrent tonsillitis is a chronic, biofilm-related infection that is a significant burden to patients and healthcare systems. It is often treated with repeated courses of antibiotics, which contributes to antimicrobial resistance. Studying biofilms is key to understanding this disease. In vitro modelling using 3D bioprinted hydrogels is a promising approach to achieve this. A novel gelatin-PEGDA pseudomonas fluorescens-laden bioink was developed and bioprinted in a 3D hydrogel construct fabricated using computer-aided design to mimic the tonsillar biofilm environment. The bioprinted constructs were cultured at 37 °C in lysogeny broth for 12 days. Bacterial growth was assessed by spectrophotometry. Cellular viability analysis was conducted using optical fluorescence microscopy (FDA/PI staining). A biocompatible 3D-printed bacteria-laden hydrogel construct was successfully fabricated. Bacterial growth was observed using optical fluorescence microscopy. A live/dead cellular-staining protocol demonstrated bacterial viability. Results obtained after the 12-day culture period showed higher bacterial growth in the 1% gelatin concentration construct compared to the 0% control. This study demonstrates the first use of a bacteria-laden gelatin-PEGDA hydrogel for biofabrication of a 3D-printed construct designed to model acute recurrent tonsillitis. Initiating a study with clinically relevant ex vivo tonsil bacteria will be an important next step in improving treatment of this impactful but understudied disease.

Impact of the COVID-19 pandemic on stage and incidence of head and neck cancer: A rapid review and meta-analysis.

OBJECTIVES: This rapid review aims to evaluate the impact of the COVID-19 pandemic on incidence of head and neck cancer (HNC) and stage distribution at diagnosis. DESIGN: Rapid review and meta-analysis. PARTICIPANTS: Comparative data for new HNC patients between a pre-pandemic cohort (before March 2020) and a pandemic cohort (after March 2020 during the lockdown period). MAIN OUTCOMES MEASURED: Data on tumour stage, incidence, referral pathway (number of new patient referrals), or workload levels (number of HNC treatments). Data on stage were summarised as odds ratios (OR) with 95% confidence intervals (CI), and data related to changes in numbers of diagnoses, referrals, and workload levels were summarised as a narrative synthesis. RESULTS: A total of 31 reports were included in this review. Individually 16 out of 23 studies did not show a significant impact on stage relative to the pre-pandemic period. However, the meta-analysis revealed that patients diagnosed with HNC during the pandemic were 16% more likely to have nodal involvement (OR = 1.16; 95% CI 1.00-1.35), 17% more likely to have a late overall stage (OR = 1.17; 95% CI 1.01-1.36), and 32% more likely to present with advanced tumour extent (T3 and T4 stage) (OR = 1.32; 95% CI 1.08-1.62). Data on incidence was extremely limited and not currently sufficient to assess trends in burden of disease. CONCLUSIONS: This review indicates that during the COVID-19 pandemic, there was upstaging of HNC at diagnosis, suggesting the provision of care to HNC patients was significantly affected.

Nanoparticle-mediated Photodynamic Therapy as a Method to Ablate Oral Cavity Squamous Cell Carcinoma in Preclinical Models.

Photodynamic therapy (PDT) is a tissue ablation technique able to selectively target tumor cells by activating the cytotoxicity of photosensitizer dyes with light. PDT is nonsurgical and tissue sparing, two advantages for treatments in anatomically complex disease sites such as the oral cavity. We have previously developed PORPHYSOME (PS) nanoparticles assembled from chlorin photosensitizer-containing building blocks (∼94,000 photosensitizers per particle) and capable of potent PDT. In this study, we demonstrate the selective uptake and curative tumor ablation of PS-enabled PDT in three preclinical models of oral cavity squamous cell carcinoma (OCSCC): biologically relevant subcutaneous Cal-33 (cell line) and MOC22 (syngeneic) mouse models, and an anatomically relevant orthotopic VX-2 rabbit model. Tumors selectively uptake PS (10 mg/kg, i.v.) with 6-to 40-fold greater concentration versus muscle 24 hours post-injection. Single PS nanoparticle-mediated PDT (PS-PDT) treatment (100 J/cm2, 100 mW/cm2) of Cal-33 tumors yielded significant apoptosis in 65.7% of tumor cells. Survival studies following PS-PDT treatments demonstrated 90% (36/40) overall response rate across all three tumor models. Complete tumor response was achieved in 65% of Cal-33 and 91% of MOC22 tumor mouse models 14 days after PS-PDT, and partial responses obtained in 25% and 9% of Cal-33 and MOC22 tumors, respectively. In buccal VX-2 rabbit tumors, combined surface and interstitial PS-PDT (200 J total) yielded complete responses in only 60% of rabbits 6 weeks after a single treatment whereas three repeated weekly treatments with PS-PDT (200 J/week) achieved complete ablation in 100% of tumors. PS-PDT treatments were well tolerated by animals with no treatment-associated toxicities and excellent cosmetic outcomes. SIGNIFICANCE: PS-PDT is a safe and repeatable treatment modality for OCSCC ablation. PS demonstrated tumor selective uptake and PS-PDT treatments achieved reproducible efficacy and effectiveness in multiple tumor models superior to other clinically tested photosensitizer drugs. Cosmetic and functional outcomes were excellent, and no clinically significant treatment-associated toxicities were detected. These results are enabling of window of opportunity trials for fluorescence-guided PS-PDT in patients with early-stage OCSCC scheduled for surgery.

Multimodal optical mesoscopy reveals the quantity and spatial distribution of Gram-positive biofilms in ex vivo tonsils.

Biofilms are known to be present in tonsils, but little is known about their spatial location and size distribution throughout the tonsil. Studies of the location and distribution of biofilms in tonsil specimens have thus far been limited to either high-magnification methods such as electron microscopy, which enables high-resolution imaging but only from a tiny tissue volume, or lower magnification techniques such as light microscopy, which allow imaging of larger specimens but with poor spatial resolution. To overcome these limitations, we report the use of multimodal optical mesoscopy to visualise and quantify the number and spatial distribution of Gram-positive biofilms in fresh, excised paediatric tonsils. This methodology supports simultaneous imaging of both the tonsil host and biofilms in whole mounts of tissue up to 5 mm × 5 mm × 3 mm with subcellular resolution throughout. A quantitative assessment of 36 tonsil specimens revealed no statistically significant difference between biofilm presence on the tonsil surface and the interior of the tonsil. This new quantitative mesoscale imaging approach may prove useful in understanding the role of biofilms in tonsillar diseases and other infections.

Digital health in head and neck cancer: a systematic review.

OBJECTIVE: Digital health tools are increasingly being recognised as effective interventions in monitoring chronic health conditions. This systematic review addressed how digital health is currently utilised in patients with head and neck cancer as an adjunct to care. METHOD: Studies of the development or evaluation of an eHealth, telemedicine or telemonitoring tool were eligible. A narrative synthesis was performed as per Preferred Reporting Items for Systematic Review and Meta-Analyses reporting guidelines. RESULTS: Twenty-nine studies of digital health tools in head and neck cancer were identified. Nine were randomised, controlled trials but most had concern of bias. Fourteen (48 per cent) of the interventions used multiple modes of delivery. The primary digital tool functions are symptom tracking and self-care, prehabilitation and rehabilitation, psychological support, and education, including decision aids. Most tools aimed to support patients during active cancer treatment. CONCLUSION: There are a small number of digital health tools for head and neck cancer patients; however, there is a lack of well-designed randomised, controlled trials to demonstrate effectiveness.

The COVID-19 pandemic has not changed stage at presentation nor treatment patterns of head and neck cancer: A retrospective cohort study.

OBJECTIVES: To evaluate the impact of the COVID-19 lockdown measures on HNC, by comparing the stage at presentation and treatment of HNC before and after the most severe COVID-19 restrictions. DESIGN: A retrospective cohort study. SETTING: A regional cancer network serving a patient population of 2.4 million. PARTICIPANTS: Newly diagnosed patients with HNC between June and October 2019 (pre-pandemic) and June and October 2021 (post-pandemic). MAIN OUTCOME MEASURES: Symptom duration before diagnosis, stage at diagnosis, patient performance status (PS) and intent of treatment delivered (palliative vs. curative). RESULTS: Five hundred forty-five patients were evaluated-250 in the 2019 and 295 in the 2021 cohort. There were no significant differences in symptom duration between the cohorts (p = .359) or patient PS (p = .821). There were no increased odds of presenting with a late (Stage III or IV) AJCC cancer stage in 2021 compared with 2019 (odds ratio [OR] = 0.90; 95% confidence interval [CI]: 0.76-1.08); nor increased odds of receiving palliative rather than curative treatment in 2021 compared with 2019 (OR = 0.68; 95% CI: 0.45-1.03). CONCLUSION: The predicted stage shift to more advanced disease at the time of diagnosis of HNC due to the COVID-19 pandemic has not been realised in the longer term. In keeping with this, there was no difference in symptom duration, patient PS, or treatment patterns between the 2019 and 2021 cohorts.

Does recreational drug use influence survival and morbidity associated with laryngeal cancer.

Background: The use of opioids is considered a risk factor for laryngeal cancer. A retrospective study was performed to explore the relationship between recreational drug exposure and laryngeal cancer. Methods: Patients diagnosed between the 1st of January 2013 and the 31st of December 2017 using ICD-10 CD-32 coding were identified from the Head and Neck Multidisciplinary Team database. We divided the study population into two cohorts (RD and non-RD) and compared the demographics, morbidity, and outcomes of these two populations. In addition, we performed case-matched analysis to control for potential confounding factors including gender, alcohol use and cigarette smoking. Findings: 329 patients in Glasgow, Scotland were included with a mean age of 64.96 ± 10.94 and a follow-up of 24 ± 13.91 months. Of these, 39 reported recreational drug use (RD). RD was associated with younger age (53.0 vs. 66.6, p<0.001) at diagnosis with laryngeal cancer. A greater proportion of tumours occurred in the supraglottic subsite (p=0.041). Furthermore, these patients were more likely to undergo tracheostomy (RR=2.50, 95% CI: 1.41-4.44, p=0.008) and laryngectomy (RR=2.25, 95% CI: 1.57-3.21, p<0.001). Recreational drug users were more likely to require enteral feeding support (RR= 1.44, 95% CI: 1.13-1.84, p=0.02) during oncological treatment. No survival differences were noted at 1, 2, or 3-years (plog-rank=0.83). Case matched analysis correcting for smoking, alcohol and gender confirmed that recreational drug users were younger at diagnosis with a predilection for the supraglottic subsite. Conclusion: Recreational drug use is associated with an increased burden of disease and morbidity in laryngeal cancer. We suggest that clinicians view recreational drug exposure as a red flag in those with suspected laryngeal cancer regardless of patient age.

Twenty-year observational study of paediatric tonsillitis and tonsillectomy.

INTRODUCTION: Tonsillectomy is now only indicated in the UK when specific criteria are met, as outlined by the Scottish Intercollegiate Guidelines Network (SIGN) and The National Institute for Health and Care Excellence (NICE). As a result, fewer numbers of tonsillectomy are being performed. Tonsillectomy is the primary treatment for recurrent tonsillitis; therefore, we hypothesise that acute admissions to hospital with tonsillitis and infective complications will have risen since criteria were introduced. Our aim was to assess the rates of acute hospital admissions with tonsillitis in children and the factors associated with this. METHODS: Data were provided by Information Service Division for all under 16s in Scotland between 1996/1997 and 2016/2017. Socioeconomic background was determined from the Scottish Index of Multiple Deprivation (SIMD) score. Poisson regression analysis was used to model predictors of surgery and correlation analysis to study the relationship between tonsillitis and other factors. RESULTS: 60 456 tonsillectomies were performed. The number of tonsillectomies dropped significantly following the introduction of SIGN guidelines, and the rates of tonsillitis increased; however, admissions with tonsillitis were already on an upward trajectory. Children from the most deprived areas were 72.0% (95% CI 60% to 85%, p<0.001) more likely to receive tonsillectomy and were also more likely to be admitted with tonsillitis than the least deprived areas. CONCLUSION: Tonsillectomy and tonsillitis rates are highest in the most deprived; postulated reasons include antibiotic stewardship and difficulty accessing primary care. Current guidelines on tonsillectomy may be disproportionately harmful in children from deprived households.

Palliation of head and neck cancer: a review of the unique difficulties.

Each year, there are 11 900 new diagnoses of head and neck cancers in the UK, with around 4000 deaths. Survival rates are higher for those diagnosed earlier, however, patients are often diagnosed later, with 20% palliative at the time of diagnosis. There is a scarcity of head and neck cancer palliative care literature available. This review article aims to discuss the unique challenges of head and neck cancer palliation. It specifically focusses on the challenges of pain management, airway obstruction, dysphagia, haemorrhage and the psychology of palliative head and neck cancer management. This article explores the advantages and disadvantages of many of the different treatment options available. It is hoped that this article will highlight the unique difficulties encountered by patients with head and neck cancer towards the end of their life and offer insights and suggestions to improve patients' quality of life in their final weeks and months.

Prognostic scores in laryngeal cancer.

PURPOSE: To evaluate the utility of various pre-treatment prognostic scoring systems for overall survival (OS) in laryngeal cancer, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), modified Glasgow Prognostic Score (mGPS) and systemic immune-inflammatory index (SIII). METHODS: We undertook a retrospective 5-year study of 220 patients with laryngeal squamous cell carcinoma undergoing active treatment. RESULTS: On multivariate analysis, low NLR (≤ 2.415, p = 0.001, OR 3.851), low PLR (≤ 269.855, p = 0.002, OR 5.520), high LMR (> 2.225, p < 0.001, OR 0.458) and low SIII (≤ 1144.465, p = 0.003, OR 3.673) were significantly associated with improved OS, accounting for confounding factors of tumour subsite, T-stage and performance status. C-reactive protein (CRP) alone (p = 0.264) and mGPS (p = 0.350) were not significantly associated with OS. CONCLUSIONS: NLR, PLR, LMR and SIII represent inexpensive, easily obtainable adjuvant decision-making tools which could help tailor individualised treatment regimes. Further investigation into the utility of combination scores and the role of different laryngeal subsites may be of interest.

Cell-free DNA and circulating tumor cell kinetics in a pre-clinical head and neck Cancer model undergoing radiation therapy.

BACKGROUND: Monitoring circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), known as liquid biopsies, continue to be developed as diagnostic and prognostic markers for a wide variety of cancer indications, mainly due to their minimally invasive nature and ability to offer a wide range of phenotypic and genetic information. While liquid biopsies maintain significant promising benefits, there is still limited information regarding the kinetics of ctDNA and CTCs following radiation therapy which remains a vital treatment modality in head and neck cancers. This study aims to describe the kinetics of ctDNA and CTCs following radiation exposure in a preclinical rabbit model with VX2 induced buccal carcinoma. METHODS: Seven rabbits were inoculated with VX2 cells in the buccal mucosa and subjected to radiation. At selected time points, blood sampling was performed to monitor differing levels of ctDNA and CTC. Plasma ctDNA was measured with quantitative PCR for papillomavirus E6 while CTCs were quantified using an immunomagnetic nanoparticles within a microfluidic device. Comparisons of CTC detection with EpCAM compared to multiple surface markers (EGFR, HER2 and PSMA) was evaluated and correlated with the tumor size. RESULTS: Plasma ctDNA reflects the overall tumor burden within the animal model. Analysis of correlations between ctDNA with tumor and lymph node volumes showed a positive correlation (R = 0.452 and R = 0.433 [p < 0.05]), respectively. Over the course of treatment, ctDNA levels declined and quickly becomes undetectable following tumor eradication. While during the course of treatment, ctDNA levels were noted to rise particularly upon initiation of radiation following scheduled treatment breaks. Levels of CTCs were observed to increase 1 week following inoculation of tumor to the primary site. For CTC detection, the use of multiple surface markers showed a greater sensitivity when compared to detection using only EpCAM. Plasma CTC levels remained elevated following radiation therapy which may account for an increased shedding of CTCs following radiation. CONCLUSION: This study demonstrates the utility of ctDNA and CTCs detection in response to radiation treatment in a preclinical head and neck model, allowing for better understanding of liquid biopsy applications in both clinical practice and research development.