Andy Ness

Background The Big Data for Quality of Life (BD4QoL) study investigates quality of life (QoL) in head and neck cancer (HNC) survivors, focusing on survivorship and characterizing survivor demographics. Methods We screened data from 5 studies across Europe (N=7276) and included patients with a diagnosis of squamous cell carcinoma (oral cavity, hypopharynx, larynx, oropharynx, nasal cavity and paranasal sinuses), treated with curative intent, alive after treatment, TNM 7th ed. stages I, II, III, IVa and IVb, with availability of QoL questionnaires. Results The cohort of 4448 HNC survivors primarily includes men (78%) with median age 61 years. Most received radiotherapy (75%) and had a history of smoking (78%). Survivors' scores on EORTC QLQ-C30 functioning scales indicated high functioning, with prevalent symptoms of fatigue, pain, and insomnia. Lower rates of missing data were observed in older patients, those with higher education and income levels, nonsmokers, married individuals, and patients not treated with radiotherapy. The odds ratios ranged from 0.47 to 0.99, indicating these factors may predict more consistent QoL data reporting in HNC survivors. Conclusions These data support the development and validation of clinical prediction models for QoL in HNC survivors in a multicentre randomized controlled trial.

Background Poor oral health has been identified as a prognostic factor potentially affecting the survival of patients with head and neck squamous cell carcinoma. However, evidence to date supporting this association has emanated from studies based on single cohorts with small-to-modest sample sizes. Methods Pooled analysis of 2449 head and neck squamous cell carcinoma participants from 4 studies of the International Head and Neck Cancer Epidemiology Consortium included data on periodontal disease, tooth brushing frequency, mouthwash use, numbers of natural teeth, and dental visits over the 10 years prior to diagnosis. Multivariable generalized linear regression models were used and adjusted for age, sex, race, geographic region, tumor site, tumor-node-metastasis stage, treatment modality, education, and smoking to estimate risk ratios (RR) of associations …

A growing proportion of head and neck cancer (HNC), especially oropharyngeal cancer (OPC), is caused by human papillomavirus (HPV). There are several markers for HPV‐driven HNC, one being HPV early antigen serology. We aimed to investigate the diagnostic accuracy of HPV serology and its performance across patient characteristics. Data from the VOYAGER consortium was used, which comprises five studies on HNC from North America and Europe. Diagnostic accuracy, that is, sensitivity, specificity, Cohen's kappa and correctly classified proportions of HPV16 E6 serology, was assessed for OPC and other HNC using p16INK4a immunohistochemistry (p16), HPV in situ hybridization (ISH) and HPV PCR as reference methods. Stratified analyses were performed for variables including age, sex, smoking and alcohol use, to test the robustness of diagnostic accuracy. A risk‐factor analysis based on serology …

Objectives To estimate both the association of surgical variables in complete unilateral cleft lip and palate (cUCLP) in the UK with outcomes at age 5 years, and the association of secondary speech surgery, volume of surgery, and surgeon with the same outcomes. Setting and Sample Population The Cleft Care UK study, a cross‐sectional study of 268 5‐year‐olds, born from 2005 to 2007, with cUCLP. Materials and Methods Information on surgical variables was extracted from a standardized questionnaire. Dento‐facial outcomes were derived from dental study casts of dental arch relationships. Three speech outcomes – intelligibility, structure and articulation – were derived using the Cleft Audit Protocol for Speech‐Augmented tool. Results Surgical and outcome data were available for 211 (79%) children from all cleft centres in the UK. Later soft palate surgery was associated with a 17% increased chance of a …

Simple Summary IgA and IgG antibodies against Epstein-Barr virus (EBV) proteins in human serum are well-known markers for EBV-positive nasopharyngeal carcinoma (NPC). Bead-based multiplex serology assays can characterize antibodies against several antigens simultaneously; however, these assays were, so far, specific for single antibody isotypes. Here, we describe the development of a duplex serological multiplex assay for the simultaneous detection of EBV IgA and IgG antibodies in a combined assay. The novel duplex assay decreases costs and effort for future epidemiological studies in EBV and NPC research and could serve as a model for other duplex multiplex applications. Abstract Epstein-Barr virus (EBV) IgA and IgG antibodies in serum from nasopharyngeal carcinoma (NPC) patients are well-established markers for EBV-positive NPC. Luminex-based multiplex serology can analyze antibodies to multiple antigens simultaneously; however, the detection of both IgA and IgG antibodies requires separate measurements. Here we describe the development and validation of a novel duplex multiplex serology assay, which can analyze IgA and IgG antibodies against several antigens simultaneously. Secondary antibody/dye combinations, as well as serum dilution factors, were optimized, and 98 NPC cases matched to 142 controls from the Head and Neck 5000 study (HN5000) were assessed and compared to data previously generated in separate IgA and IgG multiplex assays. EBER in situ hybridization (EBER-ISH) data available for 41 tumors was used to calibrate antigen-specific cut-offs using …

The aim of this study is to investigate the prognostic role of body mass index (BMI) and survival from head and neck cancer (HNC).

Background This study was designed to identify common genetic susceptibility and shared genetic variants associated with acute radiation-induced toxicity across 4 cancer types (prostate, head and neck, breast, and lung). Methods A genome-wide association study meta-analysis was performed using 19 cohorts totaling 12 042 patients. Acute standardized total average toxicity (STATacute) was modelled using a generalized linear regression model for additive effect of genetic variants, adjusted for demographic and clinical covariates (rSTATacute). Linkage disequilibrium score regression estimated shared single-nucleotide variation (SNV—formerly SNP)–based heritability of rSTATacute in all patients and for each cancer type. Results Shared SNV-based heritability of STATacute among all cancer types was estimated at 10% (SE = 0.02) and was …

Abstract A recent World Health Organization report states that at least 40% of all cancer cases may be preventable, with smoking, alcohol consumption, and obesity identified as three of the most important modifiable lifestyle factors. Given the significant decline in smoking rates, particularly within developed countries, other potentially modifiable risk factors for head and neck cancer warrant investigation. Obesity and related metabolic disorders such as type 2 diabetes (T2D) and hypertension have been associated with head and neck cancer risk in multiple observational studies. However, adiposity has also been correlated with smoking, with bias, confounding or reverse causality possibly explaining these findings. To overcome the challenges of observational studies, we conducted two-sample Mendelian randomization (inverse variance weighted [IVW] method) using genetic variants which were robustly associated with adiposity, glycaemic and blood pressure traits in genome-wide association studies (GWAS). Outcome data were taken from the largest available GWAS of 6034 oral and oropharyngeal cases, with 6585 controls. We found limited evidence of a causal effect of genetically proxied body mass index (BMI; OR IVW= 0.89, 95% CI 0.72–1.09, p= 0.26 per 1 standard deviation in BMI [4.81 kg/m2]) on oral and oropharyngeal cancer risk. Similarly, there was limited evidence for related traits including T2D and hypertension. Small effects cannot be excluded given the lack of power to detect them in currently available GWAS.

BACKGROUND: This study was designed to identify common genetic susceptibility and shared genetic variants associated with acute radiation-induced toxicity (RIT) across four cancer types (prostate, head and neck, breast, and lung).METHODS: A GWAS meta-analysis was performed using 19 cohorts including 12,042 patients. Acute standardized total average toxicity (rSTATacute) was modelled using a generalized linear regression model for additive effect of genetic variants adjusted for demographic and clinical covariates. LD score regression estimated shared SNP-based heritability of rSTATacute in all patients and for each cancer type.RESULTS: Shared SNP-based heritability of STATacute among all cancer types was estimated at 10%(se= 0.02), and was higher for prostate (17%, se= 0.07), head and neck (27%, se= 0.09), and breast (16%, se= 0.09) cancers. We identified 130 suggestive associated SNPs with rSTATacute (5.0 x10-8< P-value< 1.0 x10-5) across 25 genomic regions. rs142667902 showed the strongest association (effect allele A; effect size-0.17; P-value= 1.7 x10-7), which is located near DPPA4, encoding a protein involved in pluripotency in stem cells, which are essential for repair of radiation-induced tissue injury. Gene-set enrichment analysis identified'RNA splicing via endonucleolytic cleavage and ligation'(P= 5.1 x10-6, Pcorrected= 0.079) as the top gene set associated with rSTATacute among all patients. In-silico gene expression analysis showed the genes associated with rSTATacute were statistically significantly up-regulated in skin (not sun exposed Pcorrected= 0.004; sun exposed Pcorrected= 0.026 …

BackgroundWe examined associations between objectively-measured physical activity, depressive-symptoms, and emotional and behavioural difficulties in adolescents from a UK cohort.MethodData from 4755 participants (45% male) from the Avon Longitudinal Study of Parents and Children (ALSPAC) with physical activity assessed by accelerometry at age 11 was analysed. Indication of depressive symptoms (Short Moods and Feelings questionnaire) were obtained from parental reports at age 11 and self-reports at age 13. Behavioural and emotional problems were assessed by parents and teachers at age 11 and 13 using the Strengths and Difficulties Questionnaire (SDQ).ResultsAt age 11, males averaged 29 minutes (SD = 17) of daily moderate-to-vigorous physical activity (MVPA) compared with 18 minutes (SD = 12) among females. Higher MVPA at age 11 was associated with decreased depressive …

Head and neck cancer is often diagnosed late and prognosis for most head and neck cancer patients remains poor. To aid early detection, we developed a risk prediction model based on demographic and lifestyle risk factors, human papillomavirus (HPV) serological markers and genetic markers. A total of 10 126 head and neck cancer cases and 5254 controls from five North American and European studies were included. HPV serostatus was determined by antibodies for HPV16 early oncoproteins (E6, E7) and regulatory early proteins (E1, E2, E4). The data were split into a training set (70%) for model development and a hold‐out testing set (30%) for model performance evaluation, including discriminative ability and calibration. The risk models including demographic, lifestyle risk factors and polygenic risk score showed a reasonable predictive accuracy for head and neck cancer overall. A risk model that also …

Patients surviving head and neck cancer (HNC) suffer from high physical, psychological, and socioeconomic burdens. Achieving cancer-free survival with an optimal quality of life (QoL) is the primary goal for HNC patient management. So, maintaining lifelong surveillance is critical. An ambitious goal would be to carry this out through the advanced analysis of environmental, emotional, and behavioral data unobtrusively collected from mobile devices. The aim of this clinical trial is to reduce, with non-invasive tools (i.e., patients’ mobile devices), the proportion of HNC survivors (i.e., having completed their curative treatment from 3 months to 10 years) experiencing a clinically relevant reduction in QoL during follow-up. The Big Data for Quality of Life (BD4QoL) study is an international, multicenter, randomized (2:1), open-label trial. The primary endpoint is a clinically relevant global health-related EORTC QLQ-C30 QoL deterioration (decrease ≥10 points) at any point during 24 months post-treatment follow-up. The target sample size is 420 patients. Patients will be randomized to be followed up using the BD4QoL platform or per standard clinical practice. The BD4QoL platform includes a set of services to allow patients monitoring and empowerment through two main tools: a mobile application installed on participants’ smartphones, that includes a chatbot for e-coaching, and the Point of Care dashboard, to let the investigators manage patients data. In both arms, participants will be asked to complete QoL questionnaires at study entry and once every 6 months, and will undergo post-treatment follow up as per clinical practice. Patients randomized to the …

Objectives To determine the priorities of patients and dental professionals concerning NHS dental treatments, the factors influencing prioritisation and the willingness to contribute towards the cost of NHS dental treatments.Methods Focus groups and interviews involving patients and practitioners informed the development of a piloted questionnaire concerning the priorities for NHS dental treatments. Patients attending three purposively selected dental settings in London and Kent, as well as dental professionals working within a large London dental hospital were recruited to participate in this initial qualitative phase. Qualitative interviews were audiotaped, transcribed verbatim and analysed using the framework approach. Subsequently, another sample of patients and dental professionals within the three dental settings and dental hospital completed a questionnaire. Regression models were used to determine the …

BackgroundWalking is a simple activity that could help to reduce the prevalence of chronic diseases in all populations. Furthermore, an inverse dose–response relationship exists between steps taken and risk of premature death and cardiovascular events in middle-aged and older adults. There is a lack of information on how to effectively engage older adults around retirement age in walking. This qualitative study explored attitudes towards walking in older people with regard to habits, intensity, preferences and strategies for increasing walking behaviour.MethodsIn-depth qualitative interviews were conducted with 26 older adults who were either close to retirement or recently retired. An inductive thematic analysis was conducted.ResultsThree themes were identified from the data; 1) Engagement and perceived value of walking; was focused on the meaning of walking for the participant and the attributes they …

IntroductionA recent World Health Organization report states that at least 40% of all cancer cases may be preventable, with smoking, alcohol consumption and obesity identified as three of the most important modifiable lifestyle factors. Established risk factors for head and neck cancer include tobacco use, alcohol consumption and human papillomavirus infection. Given the significant decline in smoking rates, particularly within developing countries, other potentially modifiable risk factors warrant investigation. Obesity and related metabolic disorders such as type 2 diabetes and hypertension have all been associated with head and neck cancer risk in multiple observational studies. However, obesity has also been correlated with other major head and neck cancer risk factors such as smoking, meaning independent effects are difficult to establish. Furthermore, selection bias, confounding or reverse causality may explain the findings from observational studies.MethodsTo overcome the challenges of observational studies, we conducted two-sample Mendelian randomization (inverse variance weighted (IVW) method) using genetic variants which were robustly associated with obesity, T2D and hypertension in genome-wide association studies (GWAS). Outcome data was taken from the largest available GWAS of 6,034 oral and oropharyngeal cases, with 6,585 controls.ResultsWe found limited evidence of a causal effect of genetically proxied body mass index (OR IVW 0.89, 95%CI 0.72–1.09, p = 0.26 per 1 SD in BMI (4.81 kg/m2)) on combined oral and oropharyngeal cancer risk. Similarly, there was limited evidence for genetically-proxied T2D (OR …

Background Debate remains regarding whether to recommend a low iodine diet (LID) before radioactive‐iodine treatment and its duration and stringency. This mixed‐methods review aimed to determine if iodine status affects treatment success, the most effective diet to reduce iodine status, and how LID impacts wellbeing. Methods Five electronic databases were searched until February 2021. An effectiveness synthesis (quantitative studies) and views synthesis (qualitative, survey, and experience‐based evidence) were conducted individually and then integrated. Quality assessment was undertaken. Results Fifty‐six quantitative and three qualitative studies were identified. There was greater ablation success for those with an iodine status of <50 mcg/L (or mcg/gCr) compared with ≥250 (odds ratio [OR] = 2.63, 95% confidence interval [CI], 1.18–5.86, n = 283, GRADE certainty of evidence very low). One …

Objectives To investigate the quality of life in patients treated with either RT or surgery alone for T1a glottic carcinoma. Design This prospective cohort study aims to assess generic‐ and disease‐specific patient‐reported QoL in patients treated with either surgery or RT for T1a glottic carcinoma. Settings Multicentre, secondary care specialist head and neck units in the UK. Participants Participants were recruited as part of the multicentre, prospective Head and Neck 5000 cohort between 2011 and 2014. Main outcome measures Baseline demographic data were collected. All participants completed the EORTC QLQ C30 and EORTC QLQ H&N35 questionnaires at baseline, 4 months, 12 months and after 36 months. Results One hundred and twenty three participants received radiotherapy only (n = 68) or surgery only (n = 55). Overall QoL scores were similar between both groups. The median (IQR) EORTC …

Objective To investigate associations between markers of social functioning (trouble with social eating and social contact), depression and health‐related quality of life (QOL) among head and neck cancer survivors. Methods This cross‐sectional analysis included individuals with oral cavity, oropharynx, larynx, salivary gland and thyroid cancers from Head and Neck 5000 alive at 12 months. Trouble with social eating and social contact were measured using items from EORTC QLQ‐H&N35 and QOL using EORTC QLQ‐C30; responses were converted into a score of 0–100, with a higher score equalling more trouble or better QOL. A HADS subscale score of ≥8 was considered significant depression. Associations between tertiles of trouble with social eating and social contact and depression and QoL were assessed using multivariable logistic and linear regression (with robust errors), respectively. Results Of …

Background:Current guidance on pre-operative fasting for clear fluids to reduce aspiration risk may result in unnecessary dehydration and more liberal fluid regimes are being advocated.Methods:This randomised single blinded crossover study used an established ultrasound protocol to measure the gastric volume of 15 healthy volunteers following the 2011 European Society of Anaesthesia (ESA)‘Perioperative Fasting in Adults and Children’guidelines (nil-by-mouth two hours before induction of anaesthesia) and the 2005 Scandinavian guidelines (150 mL water with medication up to 1 hour before induction of anaesthesia).Results:We observed that gastric volumes increased following ingestion of water in all individuals compared to their fasted states. Water left the stomach within 30 minutes following ingestion in ten individuals, and within an hour in three individuals (gastric volume< 1.5 ml kg− 1). A reduction in thirst was observed in the group allowed to drink water, whereas hunger and anxiety scores were unaffected.

Background Epigenetic clocks are biomarkers of ageing derived from DNA methylation levels at a subset of CpG sites. The difference between age predicted by these clocks and chronological age, termed “epigenetic age acceleration”, has been shown to predict age-related disease and mortality. We aimed to assess the prognostic value of epigenetic age acceleration and a DNA methylation-based mortality risk score with all-cause mortality in a prospective clinical cohort of individuals with head and neck cancer: Head and Neck 5000. We investigated two markers of intrinsic epigenetic age acceleration (IEAAHorvath and IEAAHannum), one marker of extrinsic epigenetic age acceleration (EEAA), one optimised to predict physiological dysregulation (AgeAccelPheno), one optimised to predict lifespan (AgeAccelGrim) and a DNA methylation-based predictor of mortality (ZhangScore). Cox …