University of Oulu

Almangush, A.; Bello, I.O.; Heikkinen, I.; Hagström, J.; Haglund, C.; Kowalski, L.P.; Coletta, R.D.; Mäkitie, A.A.; Salo, T.; Leivo, I. Improving Risk Stratification of Early Oral Tongue Cancer with TNM-Immune (TNM-I) Staging System. Cancers 2021, 13, 3235.

Improving risk stratification of early oral tongue cancer with TNM-Immune (TNM-I) staging system

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Author: Almangush, Alhadi1,2,3,4; Bello, Ibrahim O.1,5; Heikkinen, Ilkka1,6;
Organizations: 1Department of Pathology, University of Helsinki, 00014 Helsinki, Finland
2Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland
3Institute of Biomedicine, Pathology, University of Turku, 20520 Turku, Finland
4Faculty of Dentistry, Misurata University, Misurata 2478, Libya
5Department of Oral Medicine and Diagnostic Sciences, King Saud University College of Dentistry, Riyadh 11545, Saudi Arabia
6Department of Oral and Maxillofacial Diseases, University of Helsinki, 00014 Helsinki, Finland
7Research Programs Unit, Translational Cancer Medicine, University of Helsinki, 00014 Helsinki, Finland
8Department of Oral Pathology and Radiology, University of Turku and Turku University Hospital, 20520 Turku, Finland
9Department of Surgery, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland
10Department of Head and Neck Surgery and Otorhinolaryngology, A.C. Camargo Cancer Center, São Paulo 01509-900, Brazil
11Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, São Paulo 13083-970, Brazil
12Department of Otorhinolaryngology—Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, 00130 Helsinki, Finland
13Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet and Karolinska University Hospital, 17177 Stockholm, Sweden
14Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, 90220 Oulu, Finland
15Turku University Hospital, 20521 Turku, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.6 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2021
Publish Date: 2021-11-01


Although patients with early-stage oral tongue squamous cell carcinoma (OTSCC) show better survival than those with advanced disease, there is still a number of early-stage cases who will suffer from recurrence, cancer-related mortality and worse overall survival. Incorporation of an immune descriptive factor in the staging system can aid in improving risk assessment of early OTSCC. A total of 290 cases of early-stage OTSCC re-classified according to the American Joint Committee on Cancer (AJCC 8) staging were included in this study. Scores of tumor-infiltrating lymphocytes (TILs) were divided as low or high and incorporated in TNM AJCC 8 to form our proposed TNM-Immune system. Using AJCC 8, there were no significant differences in survival between T1 and T2 tumors (p > 0.05). Our proposed TNM-Immune staging system allowed for significant discrimination in risk between tumors of T1N0M0-Immune vs. T2N0M0-Immune. The latter associated with a worse overall survival with hazard ratio (HR) of 2.87 (95% CI 1.92–4.28; p < 0.001); HR of 2.41 (95% CI 1.26–4.60; p = 0.008) for disease-specific survival; and HR of 1.97 (95% CI 1.13–3.43; p = 0.017) for disease-free survival. The TNM-Immune staging system showed a powerful ability to identify cases with worse survival. The immune response is an important player which can be assessed by evaluating TILs, and it can be implemented in the staging criteria of early OTSCC. TNM-Immune staging forms a step towards a more personalized classification of early OTSCC.

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Series: Cancers
ISSN: 2072-6694
ISSN-E: 2072-6694
ISSN-L: 2072-6694
Volume: 13
Issue: 13
Article number: 3235
DOI: 10.3390/cancers13133235
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This research was funded by the Turku University Hospital Fund, Helsinki University Hospital Research Fund, the Finnish Cancer Society, Finska Läkaresällskapet, and the Maritza and Reino Salonen Foundation.
Copyright information: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (