Date of Award

January 2020

Document Type


Degree Name

Medical Doctor (MD)



First Advisor

Benjamin L. Judson


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.


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