The prognostic value of extranodal extension in human papillomavirus-associated oropharyngeal squamous cell carcinoma.
BACKGROUND
Extranodal (or extracapsular) extension (ENE) is an adverse prognostic factor in patients with head and neck cancers who undergo primary surgery. However, the significance of ENE in human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is not well established, and single-institution studies have not established that ENE predicts inferior outcome. The authors investigated the prognostic value of ENE in HPV-positive patients who underwent primary surgery and whether adjuvant chemoradiation improved overall survival (OS) compared with radiation alone in ENE-positive patients.


METHODS
Patients who underwent primary surgery for pathologic T1 (pT1) through pT4 tumors, pathologic N1 (pN1) through pN3 lymph node status, HPV-positive OPSCC were identified in the National Cancer Data Base from 2010 through 2012. Features associated with ENE were analyzed. Univariable and multivariable Cox regression analyses identified predictors of OS. The effect of adjuvant treatment on OS in ENE-positive cohort was also evaluated.


RESULTS
In total, 1043 patients met inclusion criteria, among whom 43.5% were ENE-positive. Of the ENE-positive patients who had treatment details available, 72% received concurrent chemoradiotherapy, 16% received radiotherapy, and 12% received no adjuvant treatment. After a median follow-up of 28.4 months, ENE was associated with worse 3-year OS (89.3% vs 93.6%; P = .01). On multivariable analysis that included involved lymph nodes, only ENE, lymphovascular invasion, pT3/pT4 tumors, and Charlson-Deyo score were associated with worse OS. Among ENE-positive patients, there was no difference in 3-year OS between those who received adjuvant concurrent chemoradiotherapy versus radiotherapy alone (89.6% vs 89.3%, respectively; P = .55). Propensity score-matched comparison revealed similar results.


CONCLUSIONS
ENE is associated with inferior OS in patients with HPV-positive OPSCC. However, OS was not better with adjuvant chemoradiotherapy compared with radiotherapy alone in ENE-positive patients. The current findings support the need for prospective studies of adjuvant chemoradiation in HPV-positive patients with ENE. Cancer 2017;123:2762-72. © 2017 American Cancer Society.
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut.
Yi
Y
An
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut.
Henry S
http://orcid.org/0000-0002-9366-8514
HS
Park
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut.
Jacqueline R
JR
Kelly
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut.
John M
JM
Stahl
Division of Otolaryngology, Department of Surgery, Yale University School of Medicine, New Haven, Connecticut.|Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.|Yale Cancer Center, New Haven, Connecticut.
Wendell G
WG
Yarbrough
Yale Cancer Center, New Haven, Connecticut.|Department of Medical Oncology, Yale University School of Medicine, New Haven, Connecticut.
Barbara A
BA
Burtness
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut.|Yale Cancer Center, New Haven, Connecticut.
Joseph N
JN
Contessa
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut.|Yale Cancer Center, New Haven, Connecticut.
Roy H
RH
Decker
Department of Radiation Oncology, University of Chicago School of Medicine, Chicago, Illinois.
Matthew
M
Koshy
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut.|Yale Cancer Center, New Haven, Connecticut.
Zain A
ZA
Husain
D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000601:surgery / Q000821:virology; D059186:Chemoradiotherapy, Adjuvant; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology* / Q000601:surgery / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000473:pathology* / Q000601:surgery / Q000821:virology; D013517:Otorhinolaryngologic Surgical Procedures; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000473:pathology*; D011379:Prognosis; D057216:Propensity Score; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D015996:Survival Rate
adjuvant therapy; chemoradiation; extranodal extension; head and neck cancer; human papillomavirus (HPV)-associated oropharyngeal carcinoma