Association of Oral Cavity and Oropharyngeal Cancer Biomarkers in Surgical Drain Fluid With Patient Outcomes | Facial Plastic Surgery | JAMA Otolaryngology–Head & Neck Surgery | JAMA Network
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Original Investigation
July 2017

Association of Oral Cavity and Oropharyngeal Cancer Biomarkers in Surgical Drain Fluid With Patient Outcomes

Author Affiliations
  • 1Division of Head and Neck Surgery, Department of Otolaryngology–Head and Neck Surgery, University of Minnesota, Minneapolis
  • 2Department of Otolaryngology–Head and Neck Surgery, Hennepin County Medical Center, Minneapolis, Minnesota
  • 3Division of General Internal Medicine, Department of Medicine, University of Minnesota, Minneapolis
  • 4Division of Biostatistics, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
JAMA Otolaryngol Head Neck Surg. 2017;143(7):670-678. doi:10.1001/jamaoto.2016.3595
Key Points

Question  Are wound fluid biomarkers in patients with oral cavity or oropharyngeal cancer associated with cancer prognosis?

Findings  In this cohort study of 20 adults after surgical extirpation, assays of wound fluid biomarkers indicated that levels of matrix metalloproteinases 1 and 3 and soluble fms-like tyrosine kinase 1 were associated with recurrence; vascular endothelial growth factor isoform A, with nodal metastasis; and basic fibroblast growth factor, with lymphovascular invasion. No biomarkers assayed showed a statistically significant association with disease-free survival.

Meaning  Measurement of biomarkers in surgical drain fluid potentially represents a novel means of assessing cancer prognosis in this population.


Importance  Survival rates for head and neck cancer have been relatively stable for several decades. Individualized prognostic indicators are needed to identify patients at risk for poorer outcomes.

Objective  To determine whether biomarker levels in surgical drain fluid of patients with head and neck cancer are associated with poor cancer outcomes.

Design, Setting, and Participants  This prospective cohort study enrolled patients with squamous cell carcinoma (SCC) of the oral cavity and oropharynx who required surgical treatment from April 1, 2011, to February 1, 2016, at a tertiary or academic care center. Twenty patients, including 14 with stage IV disease, had complete specimen collection. Differences in cytokine and MMP levels by disease outcomes were evaluated.

Interventions  Patients underwent surgical treatment with drain placement as dictated by the standard of care. Drain fluid samples were collected every 8 hours postoperatively until drains were removed because of clinical criteria. Levels of cytokines and matrix metalloproteinases (MMPs) were measured using electrochemiluminescent, patterned array, multiplex technology.

Main Outcomes and Measures  The primary clinical outcome measures were survival outcome and recurrence. The biomarkers measured included the cytokines basic fibroblastic growth factor, vascular endothelial growth factor isoform A, soluble fms-like tyrosine kinase-1 (sFlt-1), and placental growth factor (PIGF) and MMP-1, MMP-3, and MMP-9. Other clinical and pathologic cancer characteristics were recorded.

Results  In this cohort of 20 patients with SCC (15 men and 5 women; mean [SD] age, 63.5 [9.9] years), a significant association with recurrence was found for levels of MMP-1 (relative difference between groups, 2.78; 95% CI, 1.23-6.29), MMP-3 (relative difference between groups, 5.29; 95% CI, 2.14-13.05), and sFlt-1 (relative difference between groups, 3.75; 95% CI, 1.84-7.65). No biomarkers were associated with disease outcome. Vascular endothelial growth factor isoform A was associated with nodal metastasis (relative difference between groups, 1.98; 95% CI, 1.12-3.51), and basic fibroblastic growth factor was associated with lymphovascular invasion (relative difference between groups, 1.74; 95% CI, 1.02-2.97).

Conclusions and Relevance  In this pilot sample of patients with SCC of the oral cavity and oropharynx, MMP-1, MMP-3, and sFlt-1 levels in wound fluid were associated with poor clinical cancer outcomes in the form of recurrence. This finding is consistent with the literature of tumor microenvironment in saliva, serum, and tumor tissue biomarkers. To our knowledge, this report is the first of such findings in surgical drain fluid, an easily accessible means of cytokine measurement. Measurement of these biomarkers in surgical fluid potentially represents a novel means of assessing cancer prognosis in this population.