Cumulative suppressive index as a predictor of relapse free survival and overall survival in Human Papilloma Virus-negative oral squamous cell carcinomas with negative resection margins

Lauren Hum; Daniel Bethmann; Zipei Feng; Shu-Ching Chang; Alexander Eckert; Carmen Ballesteros-Merino; Claudia Keschke; Matthias Kappler; Carlo B Bifulco; Claudia Wickenhauser; Barbara Seliger; Bernard A Fox; Richard Bryan Bell

doi:10.1002/hed.26520

Cumulative suppressive index as a predictor of relapse free survival and overall survival in Human Papilloma Virus-negative oral squamous cell carcinomas with negative resection margins

Head Neck. 2021 Feb;43(2):568-576. doi: 10.1002/hed.26520. Epub 2020 Oct 23.

Authors

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Oregon Health & Science University, Portland, Oregon, USA.
² Institute of Pathology, University Hospital Halle, Halle, Germany.
³ Department of Otolaryngology, Baylor College of Medicine, Houston, Texas, USA.
⁴ Medical Data Research Center, Providence St. Joseph Health, Portland, Oregon, USA.
⁵ Department of Oral and Maxillofacial Plastic Surgery, University Hospital Halle, Halle, Germany.
⁶ Earle A. Chiles Research Institute at Robert W. Franz Cancer Center, Providence Cancer Institute, Portland, Oregon, USA.
⁷ Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle, Germany.
⁸ Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon, USA.
⁹ Providence Head and Neck Cancer Program and Clinic, Providence Cancer Institute, Portland, Oregon, USA.

PMID: 33094869
DOI: 10.1002/hed.26520

Abstract

Background: This study aimed to analyze margin status and the impact of the immune elements on recurrence in patients with oral squamous cell carcinoma (OSCC), employing a prognostic biomarker, cumulative suppressive index (CSI), which reflects FoxP3+, PD-L1+, and CD8+ cell spatial relationships in the tumor microenvironment.

Methods: Cox proportional hazards regression was used to evaluate the interactive effect of the margin by CSI discrepancy (high, 3-4 vs low, 0-2) on recurrence free survival (RFS) and overall survival (OS) in 119 patients with stage I to IVA OSCC.

Results: In cases with negative margins, multivariable analysis showed high CSI was significantly associated with worse RFS (HR = 2.59, 95% CI [1.03, 6.49], P = .04) and OS (HR = 5.49, 95% CI [1.48, 20.35], P = .01) compared to low CSI. However, high CSI was not significantly associated with recurrence in cases with positive margins.

Conclusions: Immune architecture analysis can augment our current histopathological risk assessment of margin status.

Keywords: biomarker; head and neck cancer; immunotherapy; margins; oral cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Squamous Cell* / surgery
Head and Neck Neoplasms*
Humans
Margins of Excision
Mouth Neoplasms* / surgery
Neoplasm Recurrence, Local
Papillomaviridae
Prognosis
Squamous Cell Carcinoma of Head and Neck / surgery
Tumor Microenvironment