Prognostic significance of perineural invasion in oral and oropharyngeal carcinoma

doi:10.1016/j.tripleo.2003.10.014

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology

Volume 97, Issue 4, April 2004, Pages 423-431

https://doi.org/10.1016/j.tripleo.2003.10.014 Get rights and content

Abstract

Objective

To evaluate the occurrence and prognostic significance of perineural invasion (PNI) in squamous cell carcinomas (SCC) of the oral cavity and oropharynx.

Study design

A retrospective study of 101 patients with previously untreated SCC of the oral cavity and oropharynx was undertaken to evaluate the occurrence and prognostic significance of PNI in relation to local recurrence, regional recurrence, distant metastasis and survival. The logistic regression test was used for univariate and multivariate analyses. Actuarial survival curves were determined using the Kaplan-Meier method.

Results

PNI was present in 26 (25.7%) of 101 patients and was significantly associated with tumor differentiation, lymph node metastasis, and depth of invasion. Univariate analyses showed PNI was associated with local recurrence (P = .005), regional recurrence (P = .007), and distant metastasis (P = .013). In multivariate analysis, PNI was significantly associated with regional recurrence (P = .033) and distant metastasis (P = .021), but not with local recurrence (P = .109). The 5-year disease-specific survival for patients with and without PNI was 56.6% and 94.6%, respectively (P<.0001).

Conclusion

PNI is an important predictor for outcome of patients with SCC of the oral cavity and oropharynx.

Section snippets

Materials and methods

One hundred one patients with previously untreated SCC of the oral cavity and oropharynx who were treated surgically at the First Department of Oral and Maxillofacial Surgery, Niigata University, were the subjects of this study. Patients with unresectable tumors at diagnosis and those refusing surgery were excluded from this study. There were 64 male and 37 female patients, with an average age of 60 years (range 26-86 years). The anatomic site of the primary tumor was the oral cavity in 91

Results

Twenty-nine (28.7%) patients had a recurrence or metastases, including 8 patients with recurrence at the primary site, 14 patients with metastases in the neck, and 7 patients with distant metastases. Seventy-five percent of them occurred within 1 year and 92% within 2 years after the initial treatment. Secondary surgery or irradiations were performed for 2 local and twelve neck lesions. One patient with local recurrence and 7 patients with neck recurrence were salvaged successfully with the

Discussion

Perineural spaces are well recognized routes for the extension of tumors of various histologic types arising in the head and neck region.8., 12., 13., 14., 15., 16. In the literature, the occurrence of PNI from carcinomas of the head and neck is reported to range from 6% to 30%,4., 6., 16., 17. similar to the 25.7% rate in the present study. According to the results of our study, PNI is associated with tumor thickness, differentiation, and lymph node metastasis and is an important predictor of

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Sensory nerve release of CGRP increases tumor growth in HNSCC by suppressing TILs
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Perineural invasion (PNI) and nerve density within the tumor microenvironment (TME) have long been associated with worse outcomes in head and neck squamous cell carcinoma (HNSCC). This prompted an investigation into how nerves within the tumor microenvironment affect the adaptive immune system and tumor growth.
We used RNA sequencing analysis of human tumor tissue from a recent HNSCC clinical trial, proteomics of human nerves from HNSCC patients, and syngeneic orthotopic murine models of HPV-unrelated HNSCC to investigate how sensory nerves modulate the adaptive immune system.
Calcitonin gene-related peptide (CGRP) directly inhibited CD8 T cell activity in vitro, and blocking sensory nerve function surgically, pharmacologically, or genetically increased CD8 and CD4 T cell activity in vivo.
Our data support sensory nerves playing a role in accelerating tumor growth by directly acting on the adaptive immune system to decrease Th1 CD4 T cells and activated CD8 T cells in the TME. These data support further investigation into the role of sensory nerves in the TME of HNSCC and points toward the possible treatment efficacy of blocking sensory nerve function or specifically inhibiting CGRP release or activity within the TME to improve outcomes.
1R01DE028282-01, 1R01DE028529-01, 1P50CA261605-01 (to S.D.K.), 1R01CA284651-01 (to S.D.K.), and F31 DE029997 (to L.B.D.).
Perineural invasion is a poor prognostic factor for sinonasal squamous cell carcinoma
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In this study, our primary objective is to elucidate the correlation between sinonasal squamous cell carcinoma (SCC) and perineural invasion (PNI), a topic that has received limited attention in prior literature. Furthermore, we have undertaken an examination of various other clinicopathological factors.
We retrospectively reviewed the medical records of patients aged ≥ 20 years with newly diagnosed sinonasal cancer and received treatment and care at a tertiary medical center. We excluded patients who did not have an SCC diagnosis, those who underwent palliative surgery, and individuals with insufficient follow-up data at the study endpoint. Ultimately, a total of 49 eligible participants were included in our further analysis.
PNI and advanced T staging were associated with increased risk of local recurrence (LR). Furthermore, PNI was significantly associated with an adverse prognosis in terms of LR-free survival. Participants with PNI had significantly worse overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS). Patients with LR had significantly worse OS, DFS, and DSS.
PNI is associated with an elevated risk of LR and reduced OS, DFS, and DSS in patients with sinonasal SCC. These findings can facilitate the formulation of more targeted and effective treatment strategies for sinonasal SCC in clinical practice.
A case of recurrent lip cancer with middle skull base invasion with response to cetuximab and paclitaxel combination chemotherapy after nivolumab monotherapy
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Cranial base invasion involves the cranial nerves, causing various neurological symptoms and seriously affecting patients’ quality of life. We encountered a 64-year-old woman with recurrent lip cancer with skull base invasion treated with nivolumab followed by cetuximab and paclitaxel (Cmab+PTX) combination chemotherapy. The therapy showed promising efficacy based on FoundationOne® CDx and achieved complete response (CR). The patient discovered an ulcer on the left side of her lip and visited our department in August 201X. She was diagnosed with left-sided lip cancer (squamous cell carcinoma, T1N0M0) and received external-beam radiation (70 Gy). However, primary-site recurrence was noted in December 201X, and she underwent tumor resection. In April 201X+ 2, she underwent neck dissection for cervical lymph node metastasis and postoperative radiation chemotherapy (60 Gy, two courses of CDDP). In February 201X+ 3, local recurrence due to tumor invasion into the middle skull base and ocular symptoms were noted. Therefore, eight nivolumab courses were administered; however, the primary tumor increased, and an oncogene panel test was performed. Based on EGFR amplification results, Cmab+PTX was administered. Recurrent metastasis is frequently associated with poor prognoses, and cytotoxic chemotherapy after immune checkpoint inhibitor therapy is effective in managing cancer recurrence and metastasis, as in the case of our patient. The patient’s ocular symptoms disappeared, indicating CR. Six years have passed since the initial diagnosis, and there is no evidence of recurrence or metastasis.
The impact of lymph node density as a predictive factor for survival and recurrence of tongue squamous cell carcinoma
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The oral tongue is considered the most frequently involved site in cases of oral squamous cell carcinoma (OSCC). Lymph node (LN) density, defined as the number of positive LNs divided by the total number of resected LNs, is considered an important prognostic factor in OSCC; however the cut-off point remains uncertain. A retrospective study was performed involving 104 patients who underwent a glossectomy procedure for oral tongue squamous cell carcinoma (OTSCC) between the years 2008 and 2018. LN density and other related prognostic factors, including pathological N-stage (pN), extranodal extension (ENE), perineural invasion (PNI), and depth of invasion (DOI), were investigated in relation to survival and recurrence rates. pN + stage, the presence of ENE, the presence of PNI, and increased DOI were found to be associated with increased LN density values, as well as lower patient survival and higher recurrence rates. The statistical analysis identified a cut-off point for LN density of 2.5%. In advanced stage disease, LN density values above 2.5% had a significant impact on the survival rate (P = 0.005), as well as the recurrence rate (P = 0.038). In conclusion, in addition to other previously known prognostic factors, LN density may serve as a strong prognostic factor for survival and recurrence in patients with advanced- and early-stage OTSCC.
Prediction of Lymphovascular and Perineural Invasion of Oral Squamous Cell Carcinoma by Combined Expression of p63 and Cyclin D1
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Objectives The aim of this study was to determine the value of immune expression of p63 and cyclin D1 in the prediction of lymphovascular invasion (LVI) and perineural invasion (PNI) in oral squamous cell carcinoma (OSCC).
Materials and Methods Clinical and histopathologic features of 65 subjects with histologically confirmed OSCC were collected. Tissue microarray blocks representing all subjects were prepared for the immunohistochemical quantification of the nuclear expression of p63 and cyclin D1 using immune ratio plugin of image J software. Image analysis was performed by two independent pathologists. Independent samples t -test, analysis of variance, and receiver operating characteristic curve tests were used for statistical analysis. The level of significance was set at p ≤ 0.05.
Results The optimum cutoff value for the prediction of LVI for p63 and cyclin D1 was found to be 100 and 93.2, respectively, while the optimum cutoff value for the prediction of PNI for p63 and cyclin D1 was found to be 95.9 and 94, respectively. p63 and cyclin D1 expression correlated with several clinicopathologic features of the studied population. p63 expression was a significant predictor of moderate/poorly differentiated OSCC compared with well-differentiated OSCC. A parallel combination of positive p63 and cyclin D1 increased the specificity of predicting LVI from 89.1% and 67.4% for either p63 or cyclin D1, respectively, to 93.5% with a positive predictive value of 92.5%. Similarly, the parallel combination of the two markers raised the specificity of predicting PNI from 70% and 77.5% for either p63 or cyclin D1, respectively, to 90% with a positive predictive value of 86.3%.
Conclusion Combined overexpression of nuclear markers p63 and cyclin D1 can be considered as a valuable independent predictor of LVI and PNI, and hence tumor progression, in OSCC.
Impact of Adjuvant Radiotherapy in Squamous Cell Carcinoma of the Oral Cavity with Perineural Invasion
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Oral and Maxillofacial SurgeryPrognostic significance of perineural invasion in oral and oropharyngeal carcinoma

Abstract

Objective

Study design

Results

Conclusion

Section snippets

Materials and methods

Results

Discussion

J Oral Maxillofac Surg

Am J Surg

Int J Radiat Oncol Biol Phys

Am J Surg

Am J Surg

Am J Surg

J Oral Maxillofac Surg

Oral Surg Oral Med Oral Pathol Oral Radiol Endod

Am J Surg

Am J Otolaryngol

J Maxillofac Surg

Oral Surg Oral Med Oral Pathol Oral Radiol Endod

J Oral Maxillofac Surg

Surgical treatment of early-stage carcinoma of the oral tongue—would adjuvant treatment be beneficial?

Head Neck Surg

Treatment of stage I and II oral tongue cancer

Head Neck

Oral and Maxillofacial Surgery
Prognostic significance of perineural invasion in oral and oropharyngeal carcinoma