Prognostic impact of extranodal extension (ENE) in surgically managed treatment-naive HPV-positive oropharyngeal squamous cell carcinoma with nodal metastasis Journal Article


Authors: Xu, B.; Saliba, M.; Alzumaili, B.; Alghamdi, M.; Lee, N.; Riaz, N.; Patel, S. G.; Ganly, I.; Dogan, S.; Ghossein, R. A.; Katabi, N.
Article Title: Prognostic impact of extranodal extension (ENE) in surgically managed treatment-naive HPV-positive oropharyngeal squamous cell carcinoma with nodal metastasis
Abstract: Extranodal extension (ENE) is a significant prognostic factor for human papilloma virus (HPV)-negative head and neck squamous cell carcinoma and is incorporated into AJCC 8th edition pN stage. It remains controversial whether ENE or the degree of ENE is prognostically relevant in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). A detailed clinicopathologic review was conducted in a large retrospective cohort of 232 surgically treated patients with HPV-positive OPSCC and nodal metastasis. Fifty-six patients (24%) had nodal metastasis with ENE. The median vertical extent of ENE was 2.9 mm (range 0.2–20.3 mm), and the median horizontal span of ENE was 2.5 mm (range: 0.3–14.0 mm). Comparing with patients without ENE, those with ENE were associated with a higher number of positive lymph nodes, lymphovascular invasion, perineural invasion, adjuvant chemotherapy, larger primary tumor size, and shorter follow up period. Patients with ENE had shortened overall survival (OS), disease specific survival (DSS), disease free survival (DFS), distant metastasis free survival (DMFS), and regional recurrence free survival (RRFS) on univariate survival analysis. The 5-year OS, DSS, and DFS were 95%, 97%, and 90% respectively for the group without ENE, and 64%, 71%, and 65% respectively for the group with ENE. On Multivariate survival analysis, the presence of ENE was an independent adverse prognostic factor for OS, DSS, and DFS. Additionally, major ENE defined as a vertical extent of ≥4 mm or irregular soft tissue deposit independently predicted shortened OS, DSS, and RFS. In conclusion, the presence of ENE, in particular major ENE, is an independent prognostic factor in HPV-positive OPSCC. Therefore, we propose to document the presence and extent of ENE for these tumors. Consideration may be given for AJCC 9th edition to include ENE into pN stage of HPV-positive OPSCC. © 2022, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
Keywords: adult; cancer survival; controlled study; survival analysis; cancer surgery; primary tumor; retrospective studies; major clinical study; overall survival; cancer recurrence; squamous cell carcinoma; carcinoma, squamous cell; cancer patient; disease free survival; cancer staging; follow up; neoplasm staging; cohort analysis; pathology; retrospective study; soft tissue; head and neck neoplasms; adjuvant chemotherapy; lymph node; cancer size; disease specific survival; head and neck tumor; perineural invasion; oropharyngeal neoplasms; papillomavirus infections; recurrence free survival; oropharynx tumor; papillomavirus infection; cancer prognosis; lymph vessel metastasis; distant metastasis free survival; extranodal extension; humans; prognosis; human; male; female; article; oropharynx squamous cell carcinoma; squamous cell carcinoma of head and neck; wart
Journal Title: Modern Pathology
Volume: 35
Issue: 11
ISSN: 0893-3952
Publisher: Nature Research  
Date Published: 2022-11-01
Start Page: 1578
End Page: 1586
Language: English
DOI: 10.1038/s41379-022-01120-9
PUBMED: 35690646
PROVIDER: scopus
PMCID: PMC10368196
DOI/URL:
Notes: Article -- Export Date: 1 December 2022 -- Source: Scopus
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MSK Authors
  1. Ronald A Ghossein
    487 Ghossein
  2. Snehal G Patel
    414 Patel
  3. Nadeem Riaz
    421 Riaz
  4. Nancy Y. Lee
    884 Lee
  5. Nora Katabi
    307 Katabi
  6. Snjezana Dogan
    190 Dogan
  7. Ian Ganly
    432 Ganly
  8. Bin   Xu
    231 Xu
  9. Maelle Fouad Saliba
    24 Saliba