Prognostic Significance of Extranodal Extension in HPV‐Mediated Oropharyngeal Carcinoma: A Systematic Review and Meta‐analysis
Liliya Benchetrit, Sina J. Torabi, Babak Givi, Bruce H. Haughey, Benjamin L. Judson
Abstract
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. The I 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.