Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May;86(6):993-1000.
doi: 10.1111/his.15406. Epub 2025 Jan 6.

Significance of location and extent of perineural invasion in early-stage oral cavity squamous cell carcinoma

Shima Mohamed  1 , Deirdre Callanan  2   3 , Patrick Sheahan  2   3   4 , Linda Feeley  1   4
Affiliations

Significance of location and extent of perineural invasion in early-stage oral cavity squamous cell carcinoma

Shima Mohamed et al. Histopathology. 2025 May.

Abstract

Aims: Perineural invasion (PNI) is associated with survival in oral cavity squamous cell carcinoma (OCSCC). There is evidence to suggest that PNI location and extent may be of additional significance. The primary aim of this study was to evaluate the prognostic ability of PNI, including location and extent, in early-stage OCSCC.

Methods and results: This was a retrospective study, with the main cohort comprising of 129 patients with pT1/T2 pN0/Nx TNM8 OCSCC. Slides were re-reviewed in cases reported as having PNI to classify location as intratumoural (IT) and/or extratumoural (ET) and extent as unifocal (UF) or multifocal (MF). Univariate and multivariate analysis assessing impact of pathological features on survival outcomes was performed. On multivariate analysis, IT PNI was significantly associated with locoregional recurrence-free survival (LRS) [odds ratio = 5.69, 95% confidence interval (CI) = 1.50-21.63, P = 0.01]. Disease-specific survival (DSS) and overall survival (OS) were non-significant. In comparison, ET PNI was predictive of LRS (odds ratio = 20.57, 95% CI = 3.48-121.73, P = 0.001), DSS (odds ratio = 40.47, 95% CI = 5.17-316.96, P = 0.0004) and OS (odds ratio = 11.92, 95% CI = 2.18-65.22, P = 0.004). Multifocal PNI was significant on univariate analysis for all three outcome parameters evaluated, but these findings were not maintained on multivariate assessment.

Conclusions: Extratumoural PNI is strongly predictive of survival outcomes, including OS, in early-stage OCSCC. These findings support the reporting of PNI location as a mandatory data element. The impact of PNI extent requires further study.

Keywords: head and neck cancer; oral cancer; perineural invasion; prognosis; squamous cell carcinoma.

PubMed Disclaimer

Figures

Figure 1
Figure 1
A, Extratumoural perineural invasion (ET PNI) bottom left, intervening muscle, invasive tumour front top right. B, Multifocal PNI. C, PNI characterised by near complete encirclement of the nerve by tumour. D. PNI characterised by partial encirclement of the nerve and invasion of the endoneurium.
Figure 2
Figure 2
Locoregional recurrence‐free survival (LRS): no perineural invasion (PNI) versus intratumoural PNI versus extratumoural PNI.
Figure 3
Figure 3
Disease‐specific survival (DSS): no perineural invasion (PNI) versus intratumoural PNI versus extratumoural PNI.
Figure 4
Figure 4
Overall survival (OS): no perineural invasion (PNI) versus intratumoural PNI versus extratumoural PNI.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Smith BD, Haffty BG. Prognostic factoris in patients with head and neck cancer. In Harrison LB, Sessions RB, Hong WK eds. Head and neck cancer: A multidisciplinary approach. Philadelphia, PA: Lippincott Williams and Wilkins, 2009; 51–75.
    1. Fagan JJ, Collins B, Barnes L, D'Amico F, Myers EN, Johnson JT. Perineural invasion in squamous cell carcinoma of the head and neck. Arch. Otolaryngol. Head Neck Surg. 1998; 124; 637–640. - PubMed
    1. Sethi S, Lu M, Kapke A, Benninger MS, Worsham MJ. Patient and tumor factors at diagnosis in a multi‐ethnic primary head and neck squamous cell carcinoma cohort. J. Surg. Oncol. 2009; 99; 104–108. - PMC - PubMed
    1. Brandwein‐Gensler M, Smith RV, Wang B et al. Validation of the histologic risk model in a new cohort of patients with head and neck squamous cell carcinoma. Am. J. Surg. Pathol. 2010; 34; 676–688. - PubMed
    1. Chinn SB, Spector ME, Bellile EL et al. Impact of perineural invasion in the pathologically N0 neck in oral cavity squamous cell carcinoma. Otolaryngol. Head Neck Surg. 2013; 149; 893–899. - PMC - PubMed