Histological features
connect to cancer and survival
Mild Dysplasia
- Slight nuclear abnormalities, most marked in the basal third of the epithelial thickness and minimal in the upper layers, where the cells show maturation and stratification.
- A few abnormalities, but no abnormal mitoses may be present, usually accompanied by keratosis and chronic inflammation.
Moderate Dysplasia
- More marked nuclear abnormalities and nucleoli tend to be present with changes most marked in the basal two-third of the epithelium, nuclear abnormalities may persist up to the surface, but cell maturation and stratification are evident in the upper layers.
- Mitoses are present in the parabasal and intermediate layers, but none is abnormal.
Severe Dysplasia
- Marked nuclear abnormalities and loss of maturation involve more than two-third of the epithelium with some stratification of the most superficial layers.
- Mitoses some of which are abnormal may be present in the upper layers.
Normal Cells may become Cancer
Leukoplakia patients with dysplasia are at increased risk of recurrence and malignant progression
- Based on prevalence estimates of 2% of the general population there are an 15M leukoplakia patients in the US (6.6M) and EU (8.9M) combined.
- Approximately 80% of leukoplakia lesions occur in the oral cavity and could be treated by a gel (as determined by market research.
- Dysplastic lesions are present in 20% of cases and represent a high-risk patient population. These patients are treated surgically today, but have a high risk of progression and recurrence
- 3–7x increased risk of progression to squamous cell carcinoma
- 30% progress to oral cancer within 10 years
- Physicians readily identify patient characteristics for which a pharmacological treatment is likely to be preferred based on the following characteristic.
- Leukoplakia can present throughout the oral cavity, with the shape and edge definition linked to cancer risk
- It is estimated that about 80% of leukoplakia occurs in the oral cavity, with the remainder in the throat or larynx.
- 60% present as homogeneous oral leukoplakia (A)
- Flat and uniform plaque with a smooth surface and well-defined margins 20 – 30% of homogeneous lesions will become cancerous.
- 40% present as non-homogeneous oral leukoplakia (B)
- Also called proliferative leukoplakia, white plaque and areas of erythema accompanied by areas that contain nodules and/or verrucous parts with ill-defined margins 50–60% of non-homogenous will become cancerous.
- Risk of progression to oral cancer statistically significantly increased with the grade of dysplasia. Most oral cancers have a premalignant lesion stage. Regular monitoring for progression of premalignant lesions is critical for the early detection and treatment of oral cancer. Oral leukoplakia, the most common potentially cancerous oral lesion, progresses to squamous cell carcinoma.
Physicians and payers aligned on dysplastic patients not recommended for surgery as the most relevant population, with possible expansion later
- Patients not recommended for surgery serve as the point of entry. The trial design and payer support for these patients is more straightforward, especially for EU payers.
- Patients not recommended for surgery serve as the point of entry. The trial design and payer support for these patients is more straightforward, especially for EU payers.
Patient Characteristic
- Patients with leukoplakia in the oral cavity
- Lesions on the gingiva, tongue, buccal mucosa and palate, are accessible regions where the gel can adhere
- Patients with confirmed diagnosis of leukoplakia with dysplasia
- All levels of dysplasia, but not cancerous as that requires more immediate excision or cancer therapies
- Oral medicine specialists noted the importance of a biopsy to exclude patients with keratosis or scarring that may look like leukoplakia
- Patients not recommended for surgery or excision
- Non-homogenous lesions: Due to their proliferative nature, these lesions are not well defined and often cover broad areas, making excision extremely difficult or impossible
- Sensitive locations: Excision from areas such as the tongue risk loss of oral function, potentially hindering a patient’s ability to eat and talk
- Additionally, patients should be undergoing cancer-related lifestyle adjustments, such as cessation of tobacco
- Oral leukoplakia (OL) has a malignant transformation rate, which means that it can develop into oral cancer over time.
Total prevalence of 1.39%
(up to 4%)
- Up to 30% risk of OLK will develop into oral cancer
- Approx. 80% of oral leukoplakia cases may be overtreated with surgery, resulting in unnecessary interventions.
- 5-year survival rate drops to 50-66% once a person develops oral cancer.
- One of the most important factors that affects the malignant transformation rate of OL is the presence and degree of epithelial dysplasia, which is a microscopic sign of abnormal cell growth and differentiation. Epithelial dysplasia can be classified into low-risk or high-risk dysplasia according to a new binary system proposed by the World Health Organization (WHO).
- Low-risk dysplasia includes mild and moderate dysplasia, while high-risk dysplasia includes severe dysplasia and carcinoma in situ.
- High-risk dysplastic OL has a significantly higher risk of malignant transformation than low-risk dysplastic OL
- A retrospective cohort study with OL found that high-risk dysplastic OL had a 4.57-fold increased risk of malignant transformation compared with low-risk dysplastic OL
- Oral cancer incidence was substantially elevated in oral leukoplakia patients.
- Risk of progression to oral cancer statistically significantly increased with the grade of dysplasia. Most oral cancers have a premalignant lesion stage. Regular monitoring for progression of premalignant lesions is critical for the early detection and treatment of oral cancer. Oral leukoplakia, the most common potentially cancerous oral lesion, progresses to squamous cell carcinoma.
- Cancers of the oral cavity (lip, oral tongue, gingiva, floor of mouth, palate, and other mouth, including buccal mucosa) account for approximately 250.000 annual incident cases. Incidence of oral cancer was substantially elevated in patients with oral leukoplakia), including enormously high risk in the first year following a leukoplakia diagnosis.
- Defined clinically based on visual examination (a white gel in the mouth), erythroplakia (a red gel in the mouth), and oral submucous fibrosis (irreversible fibrosis of the submucous tissue) as well as histopathologically based on the presence of dysplasia.
- The natural history of oral leukoplakia, the most common oral precancerous lesion, remains poorly characterized. The rate of progression of oral leukoplakia to invasive oral cancer are poorly defined.