Date of Award

January 2020

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Benjamin L. Judson

Abstract

Determine the prognostic role of extranodal extension (ENE) among patients with HPV(+) oropharyngeal squamous cell carcinoma (OPSCC) through a systematic review and meta-analysis of institutional studies. Two independent authors searched MEDLINE, EMBASE, Scopus and PubMed databases on 12/03/2019 to identify studies of HPV(+) OPSCC comparing prognostic outcomes stratified by ENE. The I2 statistic was used to determine heterogeneity. Fixed and random effects models were used to determine hazard ratios (HRs) with 95% confidence intervals (CIs). Eighteen observational studies met inclusion criteria, yielding a total of 3,606 HPV(+) OPSCC patients [1,524 ENE(+) and 2,082 ENE(-)] with a median follow-up of 49 months. The presence of pathologic (p) ENE and radiologic (r) ENE were associated with decreased overall survival (pENE HR:1.71 [95% CI: 1.20-2.43] I2=35%; rENE HR:2.64 [95% CI:1.46-4.78] I2=75%) and distant recurrence (pENE HR:3.23 [95% CI:1.25-8.33]; rENE HR:3.83 [95% CI:1.88-7.80] I2=0%). Neither pENE (HR: 0.75, p=0.67, I2=0%) nor rENE (HR: 2.03, p=0.11, I2=0%) were associated with locoregional recurrence. ENE is associated with an increased risk of all-cause mortality and recurrence with distant metastasis in a cohort of patients with HPV(+) OPSCC. These findings may be used to inform exclusion criteria for de-intensification trials and assist in refined risk stratification.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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