Oral Potentially Malignant Disorders (OPMD): What is the clinical utility of dysplasia grade?

ABSTRACT

Introduction

Oral epithelial dysplasia is considered a potential histologic precursor of subsequent squamous cell cancer. As standard clinical practice, pathologists grade dysplasia to assess risk for progression to malignancy. Except for the most advanced grade, severe dysplasia, dysplasia grading has failed to correlate well with the risk to develop invasive cancer. The questions of what process dysplasia grading best represents and what clinical utility dysplasia grading may have are explored.

Areas covered

This narrative review is based on PubMed search with emphasis on papers since 2010. Epithelial dysplasia as a precursor lesion of cancer and dysplasia grading as a risk assessment tool for progression to cancer are discussed. The close clinical association of dysplasia with known carcinogens, alcohol, and tobacco products is presented.

Expert opinion

Oral epithelial dysplasia is often, associated with prolonged exposure to tobacco and alcohol products. With reduction of carcinogen exposure, dysplasia is known to regress in some cases. It is proposed that histologic dysplasia grade together with macroscopic images of dysplastic clinical lesions be used as an educational tool to incentivize patients to reduce their known carcinogen exposure. This strategy has the potential to reduce lesion progression thereby reducing the disease burden of oral cancer.

KEYWORDS:

• Oral epithelial dysplasia
• dysplasia grade
• oral squamous cell carcinoma
• oral Potentially Malignant Disorders (OPMD)
• leukoplakia
• cancer risk
• increased cell saturation density

ARTICLE HIGHLIGHTS

• Despite recognition of oral potentially malignant disorders (OPMDs), clinical conditions known to be potential precursors to subsequent oral squamous cell carcinoma (OSCC) and major etiologic factors, the morbidity and mortality rates of OSCC patients remain unacceptably high throughout the world. This situation can be ascribed to lack of early diagnosis for potentially malignant lesions.

• Oral epithelial dysplasia (OED), the most common subset of OPMD, is graded by pathologists on the basis of histologic features with assumptions that high-grade lesions are indicative of higher risk of malignant transformation, while low-grade lesions would very rarely transform to OSCC. However, repeated clinical pathologic studies have refuted this assumption, rendering the clinical strategy to manage OPMD on the basis of OED and OED grade, ineffective.

• Genetic multi-step mutation accumulation models of oral carcinogenesis with microscopically visible nuclear and cytoplasmic changes (OED) are in keeping with current concepts of carcinogenesis in other epithelial tissues which have evolved over the past 120 years. A more focused concept increased saturation density of epithelial cells resulting in cell persistence and disturbed cell spatial dynamics should be considered as a major contributory factor to development of invasive OSCC.

• While the focus of oral pathologists for decades has been centered on the predictive value of OED presence and grade to determine progression risk, OSCC has been shown to develop in the absence of known OED and without any evidence of neoplasia seen histologically in previously and conventionally stained oral biopsies in >20% of previously biopsied cases. The various approaches to improve determination of progression risk include: 1) improve dysplasia grade classification, 2) augment dysplasia grade with adjunct biomarkers, 3) identify specific OPMDs that have elevated risk of malignant transformation irrespective of OED presence and 4) associate markers independent of OED grade or even OED itself with amount of risk to progress to OSCC.

• Recognizing that OED grade is of limited utility as a risk prediction marker for invasive OSCC and that pathologists will continue to assess OED, the clinical utility of OED grading should be re-evaluated. As OED grade has been shown to correlate with cumulative exposure to carcinogens like tobacco, alcohol and solar radiation, the authors propose a combined practice and education strategy where quantitative OED grade at biopsy together with serial quantitative observation of OPMD could be used to encourage patients to understand, follow and provide incentive to be more aware of their own disease and thereby change behavior to reduce risk factor exposure. Further, since OSCC can supervene on OPMD without OED, clinicians should be more sensitive to follow-up of clinically concerning lesions even if the biopsy report fails to detect OED.

• While the search for effective prognostic biomarkers continues, the active measures proposed, combined with further investigation of markers independent of OED and OED grade, have the potential to reduce OSCC disease burden by enabling earlier detection of suspicious lesions.

Declaration of interest

KPH Pritzker, JTK  Hwang, & D Mock have financial interests in Proteocyte Diagnostics Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.