Prognostic Relevance of HPV Infection in Cases of Anal Squamous Cell Carcinoma: A Weighted Propensity Score Analysis Open Access

Abstract

Aim: Our goal was to evaluate the prognostic relevance of Human Papilloma Virus (HPV) infection for cases of non-metastatic anal squamous cell carcinoma treated with definitive concurrent chemo-radiation in the National Cancer Database (NCDB).

Methods: The 2014 Anal Cancer NCDB was queried for non-metastatic, histologically confirmed, anal squamous cell carcinoma patients diagnosed between the years 2008 and 2013. All eligible patients were required to have documented HPV status. Subjects were then stratified into two groups: HPV+ and HPV-. Univariate analysis (UVA) was performed using the χ² test for categorical covariates and ANOVA for numerical covariates. Multivariable analysis (MVA) was performed using Cox proportional hazard model for overall survival (OS). Hazard ratios (HR) and 95% confidence intervals (CI) were generated for each covariate. To minimize selection bias, propensity score (PS) weighting was implemented to balance OS related co-variates between the cohorts.

Results: A total of 1,063 patients fit the study inclusion criteria. Patients were stratified into HPV+ (n=498, 46.8%) and HPV- (n=565, 53.2%). After PS weighting, MVA for OS showed that for men, those with HPV infection had improved OS (HR 0.60, CI 0.38-0.96; p=0.034). However, for women, HPV infection demonstrated a statistical trend towards worse OS (HR 1.47, CI 0.96-2.25; p=0.074).

Conclusion: To our knowledge, this is the largest study evaluating the impact of HPV infection on OS in patients with anal cancer. We found that HPV infection confers a statistically significant survival advantage for men with ASCC. In contrast, for women, HPV infection portrayed a statistical trend towards survival detriment. HPV infection should be considered as a prognostic variable in future anal cancer clinical trials.

Table of Contents

Introduction 1

Background & Rationale 1

Study Objective 3

Methods 4

Data Source 4

Study Population 4

Study Cohorts 5

Covariates of Interest 5

Statistical Analysis 8

Descriptive & Univariate Statistics 8

Univariate & Multivariable Survival Analysis 9

Propensity Score Analysis 10

Results 16

Descriptive Statistics 16

Univariate Association with HPV Status 18

Univariate Association with Overall Survival 18

Multivariable Survival Analysis 19

Propensity Score Analysis 20

Discussion 22

References 25

Appendix 28

About this Master's Thesis

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School	Laney Graduate School
Department	Biostatistics
Degree	MS
Submission	Master's Thesis
Language	English
Research Field	Statistics Health Sciences, Public Health Health Sciences, Oncology
Keyword	biostatistics national cancer database propensity score
Committee Chair / Thesis Advisor	Liu, Yuan, Emory University
Committee Members	Safo, Sandra E, Emory University Ko, Yi-An , Emory University

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