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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.

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Fig. 1: Extranodal extension (ENE) in HPV-positive oropharyngeal squamous cell carcinoma.
Fig. 2: The impacts of extranodal extension (ENE, top row) and the extent of ENE (bottom row) on survival.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

Research reported in this publication was supported in part by the Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute under award number P30CA008748.

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Study design and conception; BX, NK. Pathology and clinical review: BX, MS, BA, SD, RAG, NK. Database management and statistics: BX. Manuscript drafting: BX. Manuscript editing: MS, BA, MA, NL, NR, SGP, IG, SD, RAG, NK.

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Correspondence to Nora Katabi.

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The authors declare no competing interests.

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The study was approved by the institutional review board of MSKCC. All of the research meets the ethics guidelines, including adherence to the legal requirements of the country where the study was performed.

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Xu, B., Saliba, M., Alzumaili, B. et al. Prognostic impact of extranodal extension (ENE) in surgically managed treatment-naive HPV-positive oropharyngeal squamous cell carcinoma with nodal metastasis. Mod Pathol (2022). https://doi.org/10.1038/s41379-022-01120-9

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