title: The role of perineural invasion in treatment decisions for oral cancer patients: A review of the literature.
abstract: OBJECTIVE
  The role of perineural invasion (PNI) in the management of patients with oral squamous cell carcinoma (OSSC) is still controversial, and there is no consensus regarding the most appropriate therapeutic approach. The purpose of this study is to review the findings in the literature describing OSCC as a neurotropic malignancy, with the aim of correlating perineural invasion with treatment decisions and disease prognosis.
  
  
  METHODS
  A literature search was conducted of references based on the MEDLINE and Cochrane Database of Systematic Reviews, with subject keywords including four main categories: perineural invasion, perineural spread, oral squamous cell cancinoma, neurotropic carcinoma.
  
  
  RESULTS
  In this systematic review and analysis, more than 350 publications met the eligibility criteria of the authors.
  
  
  CONCLUSIONS
  Perineural invasion (PNI) is a widely recognized indicator of poor prognosis in oral cancer patients, strongly correlating with aggressive tumor behavior, disease recurrence, and increased morbidity and mortality. Elective neck dissection could be an indicator in improving neck control in PNI-positive patients, while the addition of adjuvant postoperative radiotherapy may not significantly improve survival rates. Various molecular markers have been correlated with perineural tumor spread, but further investigations are required before targeting PNI as part of advanced cancer therapies.
authors.affiliation: Department of Oral and Maxillofacial Surgery, 401 General Military Hospital, Athens, Greece. Electronic address: Ioannis.chatzistefanou@gmail.com.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Chatzistefanou
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Maryland, Baltimore, MD, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Lubek
authors.affiliation: Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Aristotele University, Thessaloniki, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Markou
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Maryland, Baltimore, MD, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Ord
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D008207:Lymphatic Metastasis; D009062:Mouth Neoplasms / Q000473:pathology* / Q000628:therapy*; D037981:Neck Dissection; D009361:Neoplasm Invasiveness; D010525:Peripheral Nerves / Q000473:pathology*; D011379:Prognosis; D018714:Radiotherapy, Adjuvant
chemical_list: D014408:Biomarkers, Tumor
keywords: Oral cancer; Perineurial invasion; Therapy