Inequality in survival of people with head and neck cancer

Background: Socioeconomic inequalities in the relationship between lower socioeconomic status and circumstances with poorer survival of people with head and neck cancer have previously been described. However, the extent and nature of socioeconomic inequality in survival of people with head and neck cancer is poorly understood and explanations for these inequalities are yet to be thoroughly investigated. In particular, the underlying determinants of inequality in survival of people with head and neck cancer is yet to be explored by comparing factors that might be more modifiable with factors that might be more difficult to modify or control. In addition, no study exists from the United Kingdom (UK) that has explored socioeconomic inequality in survival of people with head and neck cancer using individual measurements of socioeconomic status, such as household income or education level, and few studies have investigated the long-term impact of inequality on survival of people with head and neck cancer beyond five-years. Finally, no studies have examined inequality in survival of people with head and neck cancer by utilising metrics of inequality. Further investigations into socioeconomic inequality in survival of people with head and neck cancer need to be conducted to describe and compare inequality with the aim to explain the underlying drivers of inequality in survival for people with head and neck cancer in the short-term, middle-term, and long-term follow-up. Aim: This thesis has the potential to shine a light on the issue of socioeconomic inequality in survival of people with head and neck cancer. This thesis aims to inform the patients, public, clinicians, and policy makers who are involved with head and neck cancer services on the magnitude of socioeconomic inequality in survival of people with head and neck cancer, and what factors can explain these inequalities. A series of epidemiological studies of existing UK cohort studies will be conducted to explore this topic from different angles with the aim to inform policy and practice to further the development and delivery of head and neck cancer services. The overall aim of this thesis is to: describe the trends in socioeconomic determinants and inequalities in survival from head and neck cancer over calendar time and follow-up time; to understand socioeconomic inequality in survival of people with head and neck cancer; and to explain the underlying determinants and explanations of socioeconomic inequality in survival of people with head and neck cancer. In addition, multiple measurements of survival will be utilised and compared, including overall survival, disease-specific survival, and net survival estimates, as well as measurements of inequality including the slope index of inequality and the relative index of inequality. Finally, both area-based measurements and individual measurements of socioeconomic status will be utilised and compared for their association with inequality in survival of people with head and neck cancer. Methods: Four studies were conducted with the aim to explore the magnitude, extent, and underlying determinants of survival and inequality in survival of people with head and neck cancer in the UK. Chapter 2 provides an overview analysis of socioeconomic determinants in survival by utilising data from the Scottish Cancer Registry of people diagnosed with head and neck cancer between 1986 to 2015. Due to the limitations around the availability of data in cancer registries, the explanations for socioeconomic inequality were not explored in this chapter and therefore, this chapter was an epidemiological analysis of the trends and magnitude of socioeconomic inequalities in survival over time. Chapter 3 analyses the determinants of survival from head and neck cancer by utilising the Scottish Audit of Head and Neck Cancer (SAHNC), a population-based clinical cohort study of people with head and neck cancer who were diagnosed between 1999 and 2001. Multiple patient, tumour, and treatment factors were examined for their predictive ability with survival, including area-based socioeconomic deprivation. Several methods of measuring survival were compared and contrasted in this chapter, including overall survival, disease-specific survival, and net survival estimates after one year, five years, and 12 years of a diagnosis of head and neck cancer. Chapter 4 also uses the SAHNC cohort and built upon Chapter 3by exploring the drivers and explanations for the socioeconomic inequality observed after one year, five years, and 12 years of a diagnosis of head and neck cancer. The patient, tumour, and treatment factors were individually examined for their relationship with socioeconomic factors with the aim of determining the underlying causes of socioeconomic inequality in survival of people with head and neck cancer. This chapter also explored these inequalities via different survival metrics–overall survival, disease-specific survival, and net survival estimates. Chapter 5 investigated the relationship of individual socioeconomic factors and explanations for these relationships using a cohort of people with head and neck cancer that were diagnosed between 2011 and 2014 in a population-based clinical cohort study in England; Head and Neck 5000 (HN5000). This part of the thesis aimed to undertake an in-depth exploration into the nature and extent of the socioeconomic inequality in survival of people with head and neck cancer by considering both area-based and individual dimensions of socioeconomic circumstances. Multiple demographic, health, behavioural, tumour, and treatment factors were considered to help understand the relationship between socioeconomic factors and head and neck cancer survival. This analysis built upon the previous chapters with multiple individual socioeconomic measurements and several additional potential explanatory factors collected as part of a more recent cohort study of people with head and neck cancer, including human papillomavirus (HPV) status. Results: As a whole, this thesis demonstrated strong and consistent socioeconomic inequalities in survival of people with head and neck cancer. These inequalities in survival of people with head and neck cancer appeared to become worse over calendar time and also across follow-up period after one year, five years, and ten years of a diagnosis of head and neck cancer (Chapter 2–Scottish Cancer Registry). Chapter 3 found that socioeconomic status was not an independent predictor of survival in a cohort of people with head and neck cancer who were diagnosed in Scotland between the years of 1999 and 2001(SAHNC), while Chapter 4 investigated the underlying factors that may explain the original inequality that was observed in overall survival, disease-specific survival, and net survival estimates(also the SAHNC). Chapter 4 highlighted that in models that were adjusted by various patient, tumour, and treatment factors, none of the factors could individually explain the socioeconomic inequality in survival alone, suggesting that socioeconomic inequality in survival of people with head and neck cancer is complex, with multiple factors having a combined effect, including background mortality in the long-term follow-up (via net survival estimates). The studies that were carried out in Chapter 2 to Chapter 4 only utilised area-based socioeconomic measurements –mainly Carstairs Deprivation Index. Chapter 5 added to this picture by exploring inequality by using both an area-based (Index of Multiple Deprivation (IMD)Category) and individual measurements of socioeconomic status including highest education level attained, number of years spent in education, annual household income, proportion of income from benefits, and financial concerns of living with or after cancer. Only data from England in the HN5000 cohort could be included in this analysis since it was not possible to pool and standardise the varying measurements of IMD (including Scottish IMD and Welsh IMD) across these countries of the UK. This study determined that inequalities were present for all of the measurements of socioeconomic status, however inequality in highest education level, number of years spent in education, and financial concerns of living with or after cancer were explained (fully attenuated) by other factors such as age and smoking status. Inequality across both annual household income and the proportion of income from benefits partly attenuated following the adjustment of all of the potential explanatory factors, however, even after full adjustment, the relationship with survival of these factors of socioeconomic status could not be fully explained by any of the potential patient, tumour, or treatment factors that were included in this study. The secondary aim of Chapter 3 was to compare methods of measuring survival via the use of overall survival, disease-specific survival, and net survival estimates. The substantial differences between these survival metrics demonstrated the overestimation of deaths that are specific to head and neck cancer when using overall survival, and the underestimation of disease-specific mortality from using death certificates when people have died only from head and neck cancer. These results suggest that people are dying of other causes that are related to their head and neck cancer but are not as a direct result of their cancer, which ultimately increases with time following diagnosis. Therefore, the use of net survival provides a good compromise to traditional methods to estimate the true burden of head and neck cancer in long-term follow-up studies. As a result, throughout Chapter 2 to Chapter 4, net survival estimates have been provided alongside overall survival and disease-specific survival results to compare and contrast the outcomes of people with head and neck cancer. However, in Chapter 5, it was not possible to utilise net survival estimations since lifetables for this time point had not yet been generated at the time of this analysis. Discussion and Conclusions: The thesis studied socioeconomic inequality in survival of people with head and neck cancer in the UK using data from three sources –the Scottish Cancer Registry, the SAHNC cohort study of people with head and neck cancer in Scotland, and the HN5000 cohort study of people with head and neck cancer in England. As a whole, this thesis reported that inequality in survival of people with head and neck cancer is a persistent problem–a problem which seems to be getting worse. Moreover, the main premise of this thesis was to further the understanding of explanatory factors of socioeconomic inequality in survival of people with head and neck cancer. Although socioeconomic inequality in survival utilising an area-based measurement of socioeconomic status was explained by various underlying factors, inequality by annual household income and the proportion of income from benefits only attenuated following the adjustment of all potential explanatory factors for patients in England. Even after full adjustment, inequality in survival by annual household income and the proportion of income from benefits could not be explained by any of the potential underlying factors that were included in this study. Therefore, further investigations considering individual measurements of patients’ income following a diagnosis of cancer should be conducted. In addition, a number of recommendations related to policy, practice, and further research were drawn. This thesis has provided a comprehensive examination of socioeconomic inequalities in survival of people with head and neck cancer –a relatively underexplored field. The research involved in-depth analyses of multiple datasets and from a number of perspectives. It has shown that inequalities in survival are substantial and are a growing problem, and has endeavoured to explore the explanatory factors. This work provides a platform through which policy and practice development, along with evaluation and research, can be based to reduce inequalities in survival and improve the outcome for people who are diagnosed with head and neck cancer

Reviewing the epidemiology of head and neck cancer: definitions, trends and risk factors:definitions, trends and risk factors

Introduction Head and neck cancer appears to be increasing in incidence, with potential changes in aetiology proposed. This paper aims to provide a narrative overview of the epidemiological literature to describe the disease burden and trends in terms of incidence and mortality both in the UK and globally and to review the evidence on current risk factors. Methods A search was performed on multiple databases (PubMed and Epistemonikos), applying filters to identify systematic reviews and meta-analyses which investigated head and neck cancer incidence, mortality and risk factors. International and UK cancer registries and sources were searched for incidence and mortality data. Results Multiple definitions of head and neck cancer are employed in epidemiology. Globally, incidence rates have increased in recent decades, largely driven by oropharyngeal cancer. Mortality rates over the last decade have also started to rise, reflecting the disease incidence and static survival rates. Major risk factors include tobacco smoking alone and in combination with alcohol consumption, betel chewing (particularly in Southeast Asian populations) and the human papillomavirus in oropharyngeal cancer. Conclusions These epidemiological data can inform clinical and preventive service planning for head and neck cancer

Determinants of long-term survival in a population-based cohort study of patients with head and neck cancer from Scotland

Background: We investigated long‐term survival from head and neck cancer (HNC) using different survival approaches. Methods: Patients were followed‐up from the Scottish Audit of Head and Neck Cancer. Overall survival and disease‐specific survival were calculated using the Kaplan–Meier method. Net survival was calculated by the Pohar‐Perme method. Mutually adjusted Cox proportional hazards models were used to determine the predictors of survival. Results: A total of 1820 patients were included in the analyses. Overall survival at 12 years was 26.3% (24.3%, 28.3%). Disease‐specific survival at 12 years was 56.9% (54.3%, 59.4%). Net survival at 12 years was 41.4% (37.6%, 45.1%). Conclusion: Determinants associated with long‐term survival included age, stage, treatment modality, WHO performance status, alcohol consumption, smoking behavior, and anatomical site. We recommend that net survival is used for long‐term outcomes for HNC patients—it disentangles other causes of death, which are overestimated in overall survival and underestimated in disease‐specific survival

Inequality in the survival of patients with head and neck cancer in Scotland

Background: Socioeconomic inequalities impact on the survival of head and neck cancer patients, but there is limited understanding of the explanations of the inequality, particularly in long-term survival. Methods: Patients were recruited from the Scottish Audit of Head and Neck cancer from 1999 to 2001 and were linked to mortality data as at 30th September 2013. Socioeconomic status was determined using the area-based Carstairs 2001 index. Overall and disease-specific survival were calculated using the Kaplan-Meier method with 95% confidence intervals (CI’s) at one-, five- and 12-years. Cox proportional hazard models with 95% CIs were used to determine the explanations for the inequality in survival by all-cause mortality and disease-specific mortality with 95% CIs. Net survival at one-, five- and 12-years was also computed with 95% CIs. Results: Most patients were from the most deprived group, and were more likely to smoke, drink, have cancer of a higher stage and have a lower WHO Performance Status. A clear gradient across Carstairs fifths for unadjusted overall and disease-specific survival was observed at one-, five- and 12-years for patients with HNC. Multiple patient, tumour and treatment factors play a part in the inequality observed, particularly by five- and 12-years when the inequality could be explained in fully adjusted models. However, the inequality at one-year survival remained. The inequality in 12-year net survival was very small, suggesting that the inequality in the long-term may be partly attributable to background mortality. Conclusion: Explanations for the inequality in the survival of patients with HNC are not straightforward, and this study concludes that many factors play a part including multiple patient, tumour and treatment factors

Reviewing the epidemiology of head and neck cancer: definitions, trends and risk factors

Introduction Head and neck cancer appears to be increasing in incidence, with potential changes in aetiology proposed. This paper aims to provide a narrative overview of the epidemiological literature to describe the disease burden and trends in terms of incidence and mortality both in the UK and globally and to review the evidence on current risk factors.Methods A search was performed on multiple databases (PubMed and Epistemonikos), applying filters to identify systematic reviews and meta-analyses which investigated head and neck cancer incidence, mortality and risk factors. International and UK cancer registries and sources were searched for incidence and mortality data.Results Multiple definitions of head and neck cancer are employed in epidemiology. Globally, incidence rates have increased in recent decades, largely driven by oropharyngeal cancer. Mortality rates over the last decade have also started to rise, reflecting the disease incidence and static survival rates. Major risk factors include tobacco smoking alone and in combination with alcohol consumption, betel chewing (particularly in Southeast Asian populations) and the human papillomavirus in oropharyngeal cancer.Conclusions These epidemiological data can inform clinical and preventive service planning for head and neck cancer

Teaching classroom management – A potential public health intervention?

Author's manuscript version. The final published version is available from the publisher via: http://dx.doi.org/10.1108/HE-03-2014-0030© Emerald Group Publishing LimitedPurpose – The purpose of this paper is to explore the feasibility of a classroom management course as a public health intervention. Improved socio-emotional skills may boost children’s developmental and academic trajectory, while the costs of behaviour problems are enormous for schools with considerable impact on others’ well-being. Design/methodology/approach – In total, 40 teachers attended the Incredible Years (IY) Teacher Classroom Management (TCM) intervention in groups of ten. Afterwards teachers attended focus groups and semi-structured interviews were completed with headteachers to explore whether TCM was feasible, relevant and useful, research processes were acceptable and if it influenced teachers’ practice and pupils. Teachers completed standardised questionnaires about their professional self-efficacy, burnout and well-being before and after attendance. Findings – In all, 37/40 teachers completed the course. Teachers valued sharing experiences, the support of colleagues in the group and time out to reflect on practice and rehearse new techniques. Most teachers reported that they applied the strategies with good effect in their classrooms. Teachers’ questionnaires suggested an improvement in their self-efficacy in relation to classroom management (p=0.03); other scales changed in the predicted direction but did not reach statistical significance. Research limitations/implications – Although preliminary and small, these feasibility study findings suggest that it was worthwhile proceeding to a definitive randomised controlled trial (RCT). Practical implications – Should the RCT demonstrate effectiveness, then the intervention is an obvious candidate for implementation as a whole school approach. Originality/value – Successful intervention with one teacher potentially benefits every child that they subsequently teach and may increase the inclusion of socio-economically deprived children living in challenging circumstances in mainstream education. © Emerald Group Publishing Limited.National Institute for Health Research (NIHR

Disease trajectories, place and mode of death in people with head and neck cancer: findings from the ‘Head and Neck 5000’ population-based prospective clinical cohort study

Background: Few large studies describe initial disease trajectories and subsequent mortality in people with head and neck cancer. This is a necessary first step to identify the need for palliative care and associated services. Aim: To analyse data from the Head and Neck 5000 study to present mortality, place and mode of death within 12 months of diagnosis. Design: Prospective cohort study. Participants: In total, 5402 people with a new diagnosis of head and neck cancer were recruited from 76 cancer centres in the United Kingdom between April 2011 and December 2014. Results: Initially, 161/5402 (3%) and 5241/5402 (97%) of participants were treated with ‘non-curative’ and ‘curative’ intent respectively. Within 12 months, 109/161 (68%) in the ‘non-curative’ group died compared with 482/5241 (9%) in the ‘curative’ group. Catastrophic bleed was the terminal event for 10.4% and 9.8% of people in ‘non-curative’ and ‘curative’ groups respectively; terminal airway obstruction was recorded for 7.5% and 6.3% of people in the same corresponding groups. Similar proportions of people in both groups died in a hospice (22.9% ‘non-curative’; 23.5% ‘curative’) and 45.7% of the ‘curative’ group died in hospital. Conclusions: In addition to those with incurable head and neck cancer, there is a small but significant ‘curative’ subgroup of people who may have palliative needs shortly following diagnosis. Given the high mortality, risk of acute catastrophic event and frequent hospital death, clarifying the level and timing of palliative care services engagement would help provide assurance as to whether palliative care needs are being met

Presenting symptoms and long‐term survival in head and neck cancer

Objectives To assess how type and number of symptoms are related to survival in patients with head and neck cancer. Design Patients were followed up for over 10 years from the Scottish Audit of Head and Neck Cancer (national cohort of head and neck cancer patients in Scotland 1999‐2001). September 2013, cohort was linked to national mortality data. First, second and third presenting symptoms were recorded at diagnosis. Setting National prospective audit—Scotland. Participants A subset of 1589 patients, from the original cohort of 1895, who had cancer arising from one of the four main subsites; larynx, oropharynx, oral cavity and hypopharynx. Main outcome measures Median survival in relation to patients’ presenting symptoms. Results A total of 1146 (72%) males and 443 (28%) females, mean age at diagnosis 64 years (13‐95). There was a significant difference in survival in relation to the number of the patient's presenting symptoms; one symptom had a median survival of 5.3 years compared with 1.1 years for three symptoms. Patients who presented with weight loss had a median survival of 0.8 years, compared to 4.2 years if they did not (P < .001). Patients who presented with hoarseness had a median survival of 5.9 years compared to 2.6 years without (P < .001). There was no significant difference in long‐term survival for patients who presented with an ulcer, compared to those that did not (P = .105). Conclusions This study highlights the importance of patients’ presenting symptoms, giving valuable information in highlighting appropriate “red flag” symptoms and subsequent treatment planning and prognosis

Epstein-Barr virus and human papillomavirus serum antibodies define the viral status of nasopharyngeal carcinoma in a low endemic country

Epstein-Barr virus (EBV) causes nasopharyngeal carcinoma (NPC) in endemic regions, where almost every tumor is EBV-positive. In Western populations, NPC is rare, and human papillomavirus infection (HPV) has been suggested as another viral cause. We validated multiplex serology with molecular tumor markers, to define EBV-positive, HPV-positive, and EBV-/HPV-negative NPCs in the United Kingdom, and analyzed survival differences between those groups. Sera from NPC cases (N = 98) and age- and sex-matched controls (N = 142) from the Head and Neck 5000 clinical cohort study were analyzed. IgA and IgG serum antibodies against 13 EBV antigens were measured and compared with EBER in situ hybridization (EBER-ISH) data of 41 NPC tumors (29 EBER-ISH positive, 12 negative). IgG antibodies to EBV LF2 correctly diagnosed EBV-positive NPCs in 28 of 29 cases, while all EBER-ISH negative NPCs were seronegative to LF2 IgG (specificity = 100%, sensitivity = 97%). HPV early antigen serology was compared to HPV molecular markers (p16 expression, HPV DNA and RNA) available for 41 NPCs (13 positive, 28 negative). Serology matched molecular HPV markers in all but one case (specificity = 100%, sensitivity = 92%). EBV and HPV infections were mutually exclusive. Overall, 67% of the analyzed NPCs were defined as EBV-positive, 18% as HPV-positive and 14% as EBV/HPV-negative. There was no statistical evidence of a difference in survival between the three groups. These data provide evidence that both, EBV-positive and HPV-positive NPCs are present in a low incidence country, and that EBV and HPV serum antibodies correlate with the viral status of the tumor.</p

Inequality in survival of people with head and neck cancer:Head and Neck 5000 cohort study

Background: Explanations for socioeconomic inequalities in survival of head and neck cancer (HNC) patients have had limited attention and are not well understood. Methods: The UK Head and Neck 5000 prospective clinical cohort study was analyzed. Survival relating to measures of socioeconomic status was explored including area‐based and individual factors. Three‐year overall survival was determined using the Kaplan–Meier method. All‐cause mortality was investigated via adjusted Cox Proportional Hazard models. Results: A total of 3440 people were included. Three‐year overall survival was 76.3% (95% CI 74.9, 77.7). Inequality in survival by deprivation category, highest education level, and financial concerns was explained by age, sex, health, and behavioral factors. None of the potential explanatory factors fully explained the inequality associated with annual household income or the proportion of income of benefits. Conclusion: These results support the interventions to address the financial issues within the wider care and support provided to HNC patients