Multidimensional Approach to Understanding Head and Neck Cancer
Kabara, Ilona
2019
Abstract
Head and neck is the sixth most common cancer type worldwide, with the highest incidence observed in South and Southeast Asia. Comprised of a heterogeneous group of malignancies, head and neck cancers (HNC) span several anatomical subsites, including the: oral cavity, oropharynx, hypopharynx, nasopharynx, larynx, salivary glands, paranasal sinuses and nasal cavity. While ~90% of these neoplasms are morphologically characterized as squamous cell carcinoma, etiological differences across cancer subsite, along with geographic attributes that influence the variable global incidence and mortality trends, make HNC a therapeutically challenging and behaviorally variable disease. The goal of this dissertation is to improve the current state of knowledge surrounding HNC through the use of descriptive and molecular epidemiological methods. To do so, the first aim utilized several sources of cancer registry data to assess trends in head and neck, and separately nasopharyngeal, carcinoma to better understand how temporal changes in environmental and behavioral risk factors, as well as advances in clinical practices, influence cancer onset and survival. Culminating in four manuscripts, the first two focused on nasopharyngeal carcinoma (NPC); findings revealed Asian/Pacific Islanders living in the U.S., a non-endemic region, to have comparable rates of NPC incidence as those in endemic Thailand. Interestingly, the Epstein-Barr virus (EBV) related differentiated non-keratinizing subtype was shown to be increasing across nearly all gender and race groups in the U.S., while survival rates appeared to vary. The remaining studies highlighted the role of decreasing tobacco, alcohol and betel quid use, three major risk factors in HNC development, on decreasing laryngeal and oral cavity cancer rates across the U.S. and Southeast Asia. Nevertheless, as the world’s largest tobacco manufacturer and consumer of ~30% of the world’s cigarettes, Chinese males in Shanghai experienced a 9.1% annual increase in laryngeal cancer between 1998 and 2002. The reductions in tobacco use have elucidated the role of human papilloma virus (HPV) as an important causal factor in oropharyngeal carcinoma (OPC). To date, this etiological shift has almost exclusively been studied and proposed to effect Western, more developed countries. Using descriptive epidemiology in aim one to inform molecular analyses in aim two, the results of these studies challenged previous assumptions. Having undergone rapid socioeconomic change, cancer has superseded infectious disease as the leading cause of mortality in Thailand. In accordance with economic growth, changes in cultural norms have allowed for an etiological transition that has led to an increase in oral HPV infections, and consequently OPC incidence. Although far from the 80% prevalence observed in the U.S., OPC HPV rates in Thailand have increased from 16% in 2012 to 26% in 2017—expecting to exceed 50% by 2030. Despite medical advances in HNC treatment, 5-year relative survival has remained disappointingly stable at 50-60% over the past few decades. Recent studies have shown the presence of tumor-infiltrating lymphocytes to be an important prognostic tool in guiding HNC treatment. For the last aim, dietary factors, which have previously been shown to be important in HNC risk, progression and prognosis, were assessed and shown to significantly influence tumor immune response and subsequently survival. Overall, the research presented in this dissertation not only provides a better understanding of HNC on a global scale, but also offers a basis for future studies to aid in elucidating etiology and improving treatment and prevention for this highly disfiguring and deadly disease.Subjects
Head and Neck Cancer Global Epidemiology Descriptive Epidemiology Molecular Epidemiology Translational Epidemiology
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