Pretreatment pain predicts perineural invasion in patients with head and neck squamous cell carcinoma

Abstract

Objectives: Perineural invasion (PNI) in head and neck cancer (HNC) is a distinct pathological feature used to indicate aggressive tumor behavior and drive treatment strategies. Our study examined the prevalence and predictors of PNI in HNC patients stratified by tumor site.

Study design and methods: A retrospective analysis of head and neck squamous cell carcinoma (HNSCC) patients who underwent surgical resection at the University of Pittsburgh Medical Center between 2015 and 2018 was performed. Pretreatment pain was assessed at least 1 week before surgery using the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N). Demographics, clinical characteristics, and concomitant medications were obtained from medical records. Patients with cancers at the oropharynx and non-oropharynx (i.e., cancer at oral cavity, mandible, larynx) sites were separately analyzed. Tumor blocks were obtained from 10 patients for histological evaluation of intertumoral nerve presence.

Results: A total of 292 patients (202 males, median age = 60.94 ± 11.06) were assessed. Pain and PNI were significantly associated with higher T stage (p < 0.001) and tumor site (p < 0.001); patients with non-oropharynx tumors reported more pain and had a higher incidence of PNI compared to oropharynx tumors. However, multivariable analysis identified pain as a significant variable uniquely associated with PNI for both tumor sites. Evaluation of nerve presence in tumor tissue showed 5-fold higher nerve density in T2 oral cavity tumors compared to oropharyngeal tumors.

Conclusions: Our study finds that PNI is associated with pretreatment pain and tumor stage. These data support the need for additional research into the impact of tumor location when investigating targeted therapies of tumor regression.

Keywords: Head and neck cancer; Nerves; Pain; Patient-reported outcomes; Perineural invasion.

Fig. 1

Quantification of nerve presence in head and neck tumors stratified by location. A Representative S100 immunoreactivity in tumor tissue from oropharyngeal (left) and non-oropharyngeal (right) tumor tissue. Tissue was counterstained with hematoxylin. Red box in upper panels indicated area selected for 20× magnification in lower panels. Black arrows indicate S100-positive nerve bundles. B Analysis of total nerve presence across 10 patients with disease located in the oropharyngeal (white bar, n = 5) and non-oropharyngeal (gray bar, n = 5) region found higher S100 immunoreactivity in non-oropharyngeal tumor tissue. Independent t test, **p < 0.01