Early Prediction of Oral Cancer by S100A7 Immunohistochemistry Signature-based Assessment

A Multi-Centre Prospective Community-Based Observational Study on Prediction of Malignant Progression of Clinically Suspicious Oral Lesions With STRATICYTE

The purpose of this observational study is to evaluate the utility of the S100A7 immunohistochemistry signature-based assessment - STRATICYTE - in determining the risk of progression to cancer of clinically suspicious oral lesions.

Study Overview

• Status: Recruiting
• Conditions: Oral Neoplasm
• Intervention / Treatment: Procedure: Standard of Care Histopathology; Procedure: STRATICYTE Assessment

Detailed Description

Background: The standard of care for potentially premalignant oral epithelial lesion (PPOEL) risk assessment for progression to cancer is dysplasia grading by histopathology. With significant overlap between dysplasia grades and high inter- and intra-observer variations, dysplasia grading alone has been shown to be inadequate as a prognostic tool. To investigate the utility of the S100A7 immunohistochemistry signature-based assessment - STRATICYTE - in the early diagnosis of invasive oral cancer, a prospective multi-center observational study was designed with specimens obtained from community-based practices.

Methods: Patients that qualify to enroll in the study will be assessed for both standard of care histopathological assessment for dysplasia grade and STRATICYTE risk assessment, and followed for up to 60 months (from initial biopsy) to determine the outcome of their oral lesion(s).

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Jason Hwang, PhD; Phone Number: (647) 255-1370; Email: jhwang@proteocyte.com
• Study Contact Backup: Name: Mark Darling, MSc, MChD; Phone Number: 86399 (519) 661-2111; Email: mark.darling@schulich.uwo.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1C9
      • Recruiting
      • University of Alberta
      • Contact: Tim McGaw, DDS, MSc, MD
      • Principal Investigator: Tim McGaw, DDS, MSc, MD
    • Edmonton, Alberta, Canada, T5M 3Z7
      • Recruiting
      • Kingsway Oral & Maxillofacial Surgery
      • Contact: Tim McGaw, DDS, MSc, MD
      • Principal Investigator: Tim McGaw, DDS, MSc, MD
  • Ontario
    • London, Ontario, Canada, N6A 5C1
      • Recruiting
      • Western University
      • Contact: Mark Darling, MSc, MChD
      • Principal Investigator: Mark Darling, MSc, MChD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 90 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study population will be selected from community-based Oral & Maxillofacial Surgery practices in the provinces of Ontario and Alberta, Canada

Description

Inclusion Criteria:

• Any clinically suspicious lesion biopsied to rule-out oral epithelial dysplasia/oral squamous cell carcinoma

Exclusion Criteria:

• Biopsied lesion with or without dysplasia concomitant with oral squamous cell carcinoma at initial biopsy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Oral Mucosal Biopsies With or Without Evidence of Epithelial Dysplasia; No evidence of dysplasia Mild dysplasia Moderate dysplasia Severe dysplasia	Procedure: Standard of Care Histopathology; Assessment for mild, moderate, or severe dysplasia, and risk of progression to oral cancer; Other Names: H&E assessment for dysplasia grade; Procedure: STRATICYTE Assessment; Assessment for risk of progression to oral cancer; Other Names: S100A7 Immunohistochemistry Signature-based Assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Malignant Transformation Rate: Dysplasia	Cancer progression rate in patients with oral neoplasia with dysplasia and STRATICYTE Low-Risk or Elevated Risk	60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Malignant Transformation Rate: No Dysplasia	Cancer progression rate in patients with oral neoplasia without dysplasia and STRATICYTE Low-Risk or Elevated-Risk	60 months
Recurrence Rate	Recurrence rate in patients with oral neoplasia with or without dysplasia and STRATICYTE Low-Risk or Elevated-Risk	60 months

Collaborators and Investigators

• Sponsor: Proteocyte Diagnostics Inc.
• Investigators: Principal Investigator: Mark Darling, MSc, MChD, Western University

Publications and helpful links

General Publications

• Ralhan R, Desouza LV, Matta A, Tripathi SC, Ghanny S, Datta Gupta S, Bahadur S, Siu KW. Discovery and verification of head-and-neck cancer biomarkers by differential protein expression analysis using iTRAQ labeling, multidimensional liquid chromatography, and tandem mass spectrometry. Mol Cell Proteomics. 2008 Jun;7(6):1162-73. doi: 10.1074/mcp.M700500-MCP200. Epub 2008 Mar 13.
• Ralhan R, Desouza LV, Matta A, Tripathi SC, Ghanny S, Dattagupta S, Thakar A, Chauhan SS, Siu KW. iTRAQ-multidimensional liquid chromatography and tandem mass spectrometry-based identification of potential biomarkers of oral epithelial dysplasia and novel networks between inflammation and premalignancy. J Proteome Res. 2009 Jan;8(1):300-9. doi: 10.1021/pr800501j.
• Tripathi SC, Matta A, Kaur J, Grigull J, Chauhan SS, Thakar A, Shukla NK, Duggal R, DattaGupta S, Ralhan R, Siu KW. Nuclear S100A7 is associated with poor prognosis in head and neck cancer. PLoS One. 2010 Aug 3;5(8):e11939. doi: 10.1371/journal.pone.0011939.
• Kaur J, Matta A, Kak I, Srivastava G, Assi J, Leong I, Witterick I, Colgan TJ, Macmillan C, Siu KW, Walfish PG, Ralhan R. S100A7 overexpression is a predictive marker for high risk of malignant transformation in oral dysplasia. Int J Cancer. 2014 Mar 15;134(6):1379-88. doi: 10.1002/ijc.28473. Epub 2013 Oct 8.
• Hwang JT, Gu YR, Shen M, Ralhan R, Walfish PG, Pritzker KP, Mock D. Individualized five-year risk assessment for oral premalignant lesion progression to cancer. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Mar;123(3):374-381. doi: 10.1016/j.oooo.2016.11.004. Epub 2016 Nov 22.

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2015
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 4, 2020
• First Submitted That Met QC Criteria: November 4, 2020
• First Posted (Actual): November 10, 2020

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Lesion; Artificial Intelligence; Personalized Medicine; Hyperplasia; Early Diagnosis; Oral Cancer; Machine Learning; OPMD; Leukoplakia; Oral Potentially Malignant Disorder; Oral Potentially Malignant Lesion; Erythroplakia; Erythroleukoplakia; Oral Epithelial Dysplasia; S100A7 Biomarker; S100A7 Immunohistochemistry Signature-based; STRATICYTE; Oral Neoplasia; Oral Epithelial Atypia; Hyperkeratosis; Oral Squamous Cell Carcinoma; Potentially Premalignant Oral Epithelial Lesion; Mild Dysplasia; Moderate Dysplasia; Severe Dysplasia; Low-grade Dysplasia; High-grade Dysplasia; Predictive Assay; Whole Slide Imaging; Computational Pathology; Digital Pathology; OPML
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Mouth Neoplasms
• Other Study ID Numbers: PRO-STR-PPOEL-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No