Associations between Human Papillomavirus Infection and Peripheral Blood Gene Expression Among Patients with Head and Neck Cancer Before and After Radiotherapy Open Access

Abstract

Human papillomavirus (HPV) is a highly prevalent sexually transmitted infection linked to the development of some cancers, including head and neck squamous cell carcinoma (HNSCC). HNSCCs have surpassed cervical cancer as the most common HPV-related malignancy in the United States and other high-income countries. HPV-related cancers are associated with over 70% of oropharyngeal cancer cases and often have a more favorable prognosis compared to non- HPV associated HNSCC. However, the molecular mechanisms are still not fully known. This study aimed to examine the association between HPV infection and gene expression among patients with HNSCC. Blood samples were collected from 146 patients with HNSCC at baseline, before radiotherapy with or without chemotherapy, and at the end of treatment. A multiple linear regression model was used to analyze 19,556 genes and explore the association between HPV and gene expression. While 204 genes showed significant differential gene expression at baseline and 123 genes after treatment (p < 0.05), none remained significant after false discovery rate (FDR) < 0.05 adjustment. An enrichment analysis was performed among the top 100 differently expressed genes (p < 0.05). The biological processes highlighted at baseline are mainly associated with immune response and protein coding. The top biological processes revealed posttreatment include metabolic activities, gene expression, and cellular responses. Despite this, further investigation, using alternative analysis methods and a larger sample size is important to identify genes associated with the progression of HPV-related HNSCC. This research contributes to the molecular understanding of HPV-related HNSCC and emphasizes the need for continued research to identify biomarkers and targets for improved patient treatment. 

Table of Contents

Table of Contents

Introduction .....................................................................................................................................1

Descriptive Epidemiology ...........................................................................................................1

Genetic Characteristics of HNSCC .............................................................................................3

Treatment and Prognosis .............................................................................................................3

Methods ...........................................................................................................................................4

Study Design ...............................................................................................................................4

Study Population .........................................................................................................................5

Clinical and Demographic Measures...........................................................................................5

Laboratory Measures ...................................................................................................................6

Data Analysis...............................................................................................................................6

Results .............................................................................................................................................8

Demographic Characteristics.......................................................................................................8

Differentially Expressed Genes .................................................................................................10

Discussion......................................................................................................................................15

Limitations + Strengths .............................................................................................................18 Conclusion.................................................................................................................................19

References .....................................................................................................................................20

Supplemental Tables......................................................................................................................23 

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Epidemiology - MPH & MSPH
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health Health Sciences, Oncology Health Sciences, Epidemiology
Keyword	treatment human papillomavirus gene expression cancer
Committee Chair / Thesis Advisor	Joellen Schildkraut, Emory University
Committee Members	Canhua Xiao, Emory University

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