Prognostic Significance of Extranodal Extension in HPV-Mediated Oropharyngeal Carcinoma: A Systematic Review and Meta-analysis

Objective To determine the prognostic role of extranodal extension (ENE) among patients with human papilloma virus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) through a systematic review and meta-analysis of institutional studies. Data Sources MEDLINE, Embase, Scopus, and PubMed. Review Methods Two independent authors searched the databases on December 3, 2019, to identify studies of HPV+ OPSCC comparing prognostic outcomes stratified by ENE. TheI(2)statistic was used to determine study heterogeneity. Fixed and random effects models were used to determine hazard ratios (HRs) with 95% CIs. Results Eighteen observational studies met inclusion criteria, yielding 3603 patients with HPV+ OPSCC (1521 ENE+ and 2082 ENE-) with a median follow-up of 49 months. The presence of pathologic ENE (pENE) and radiologic ENE (rENE) was associated with decreased overall survival (pENE HR, 1.89 [95% CI, 1.15-3.13],I-2= 35%; rENE HR, 2.64 [95% CI, 1.46-4.78],I-2= 75%) and distant recurrence (pENE HR, 3.23 [95% CI, 1.25-8.33],I-2= 0%; rENE HR, 3.83 [95% CI, 1.88-7.80],I-2= 0%). Neither pENE nor rENE was associated with locoregional recurrence (pENE HR, 0.75 [95% CI, 0.20-2.84],I-2= 0%; rENE HR, 2.03 [95% CI, 0.86-4.79],I-2= 0%). pENE was not associated with disease-specific survival (pENE HR, 1.45 [95% CI, 0.84-2.49],I-2= 0%). Conclusion pENE and rENE are moderately 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 deintensification trials and assist in refined risk stratification.