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. 2025 Jan-Dec:54:19160216251316219.
doi: 10.1177/19160216251316219.

Perineural Invasion Unveiled: Deciphering the Prognostic Impact of Diameter and Quantity Subcategories in Oral Cancer

Hui-Wen Cheng  1 , Li-Han Lin  1   2 , Hung-Pin Lin  3   4 , Chung-Ji Liu  1   2   5
Affiliations

Perineural Invasion Unveiled: Deciphering the Prognostic Impact of Diameter and Quantity Subcategories in Oral Cancer

Hui-Wen Cheng et al. J Otolaryngol Head Neck Surg. 2025 Jan-Dec.

Abstract

Importance: Perineural invasion (PNI) is an established prognostic factor in oral squamous cell carcinoma (OSCC), but the impact of its subcategories on survival is not fully understood. This study quantifies the number and diameter of PNI foci to assess their prognostic relevance in OSCC.

Objective: To evaluate the prognostic significance of PNI subcategories, specifically the number and diameter of PNI foci, as predictors of overall survival (OS) and disease-free survival (DFS) in OSCC patients.

Design: Retrospective cohort study, adhering to STROBE guidelines.

Setting: Single-center study at MacKay Memorial Hospital, Taiwan, including patients diagnosed with OSCC from 2005 to 2018.

Participants: Nine hundred twenty-six patients with biopsy-proven OSCC, excluding those with perioperative mortality or incomplete follow-up.

Exposure: Histological evaluation of PNI, including quantifying the number and diameter of invaded nerves, along with clinicopathological features such as tumor stage and lymphovascular invasion (LVI).

Main outcome measures: OS and DFS, assessed via Cox proportional hazards models, Kaplan-Meier survival analysis, and receiver operating characteristic curve analysis for PNI foci subcategories.

Results: PNI was present in 138 (14.9%) patients and was significantly associated with adverse histologic features, advanced tumor stage, nodal involvement, metastasis, and LVI. Multivariate analysis revealed that both the number of PNI foci greater than 4 and nerve diameters exceeding 0.21 mm were significantly associated with poorer OS and DFS (P < .05). After adjusting for clinical variables, PNI remained an independent predictor of worse OS [hazard ratio (HR): 1.37] and DFS (HR: 1.46).

Conclusions and relevance: PNI is a significant independent prognostic factor in OSCC. Patients with more than 4 PNI foci or nerve involvement greater than 0.21 mm in diameter experienced significantly worse survival outcomes. These findings suggest that detailed assessment of PNI subcategories should be incorporated into OSCC management, guiding treatment decisions and potentially informing the need for adjuvant therapies.

Keywords: oral cancer; perineural invasion; prognosis; survival.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Graphical abstract
Graphical abstract
Visual Abstract
Visual Abstract
Figure 1.
Figure 1.
(A, C, and E) Kaplan–Meier analysis for overall survival according to quality and involved diameter of nerve in OSCC patients. (B, D, and F) Kaplan–Meier analysis of disease-free survival in OSCC patients. P-values were calculated by the log-rank test. OSCC, oral squamous cell carcinoma.
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