What is the etiology of recurrence of oral squamous cell carcinoma (OSCC)?

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Last updated: April 15, 2025View editorial policy

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From the Guidelines

Recurrence of oral squamous cell carcinoma is primarily caused by incomplete surgical removal of the primary tumor, field cancerization, and continued exposure to risk factors such as smoking and alcohol consumption, with up to 40% of patients suffering recurrence after therapy, as stated in the most recent study 1. The etiology of recurrence is multifactorial, involving various factors that contribute to the development of new tumors or the growth of residual cancer cells.

  • Incomplete surgical removal of the primary tumor is a significant cause, where cancer cells remain at the surgical margins or in nearby tissues, as mentioned in the study 1.
  • Field cancerization is another major factor, where multiple areas of the oral mucosa have undergone premalignant changes due to prolonged exposure to carcinogens like tobacco and alcohol, creating a favorable environment for new tumors to develop.
  • Continued exposure to risk factors such as smoking, alcohol consumption, and betel quid chewing significantly increases recurrence risk, as supported by the study 1.
  • Patients with certain genetic mutations, particularly in p53 and EGFR genes, face higher recurrence rates, although this is not explicitly mentioned in the provided studies.
  • Human papillomavirus (HPV) status can also influence recurrence patterns, with HPV-negative tumors generally having worse outcomes, as implied in the study 1.
  • Advanced initial tumor stage, poor differentiation, perineural invasion, and lymphovascular invasion are histopathological features associated with higher recurrence risk, as stated in the study 1.
  • Additionally, patients with compromised immune systems due to conditions like HIV or immunosuppressive medications have increased susceptibility to recurrence. Regular follow-up examinations every 1-3 months in the first two years after treatment are essential for early detection of recurrence, as this period represents the highest risk timeframe, with the majority of recurrences occurring in the first 2 years following treatment, as mentioned in the study 1. The management of recurrent and/or metastatic disease not amenable to curative RT or surgery involves various treatment options, including pembrolizumab monotherapy, pembrolizumab plus platinum/5-FU, and platinum/5-FU/cetuximab, as outlined in the study 1.

From the Research

Etiology of Recurrence of Oral Squamous Cell Carcinoma

The recurrence of oral squamous cell carcinoma (OSCC) is a complex phenomenon influenced by various factors. Studies have identified several clinicopathological and genetic factors associated with recurrence.

  • Clinicopathological factors:
    • T stage, degree of differentiation, and pN stage have been identified as independent factors of recurrence 2
    • Margin status, lymph node ratio, and grading of the primary tumor have been found to be significantly correlated with the timing of recurrence 3
    • Positive surgical margins, pathological T staging, and alcohol consumption have been associated with recurrence 4
  • Genetic factors:
    • Genetic profiling has revealed that the CASP8 gene is significantly altered in the recurrent group 4
    • Copy number alterations in cytoband 5p15.33, involving amplification in the telomerase reverse-transcriptase (TERT) gene, have been found to be significant in the recurrent group 4
  • Other factors:
    • The site of the primary tumor, with buccal mucosa origin being a significant risk factor for recurrence 4
    • The presence of extracapsular spread in the primary tumor and the performance of salvage treatment have been identified as independent risk factors for overall survival in patients with recurrent OSCC 3

Risk Factors for Recurrence

Several risk factors for recurrence have been identified, including:

  • Advanced T stage 2, 4
  • Poor degree of differentiation 2
  • Positive pN stage 2
  • Positive surgical margins 4
  • Lymph node ratio 3
  • Grading of the primary tumor 3
  • Alcohol consumption 4
  • Presence of extracapsular spread in the primary tumor 3

Impact of Treatment on Recurrence

Treatment modalities, such as surgery, radiation therapy, and chemotherapy, have been evaluated for their impact on recurrence.

  • Surgery has been found to significantly increase overall survival time and survival time after recurrence 5
  • Radiation therapy and chemotherapy have not been found to have a significant survival benefit as therapy for recurrence 5
  • Salvage surgery has been found to increase survival after recurrence 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Survival analysis and risk factors for recurrence in oral squamous cell carcinoma: does surgical salvage affect outcome?

Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons, 2010

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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