Evaluating Treatment Strategies for p53 Mutant Oral Cancer and Oral Cancer Precursors

Evaluating Treatment Strategies for p53 Mutant Oral Epithelial Dysplasia and SCC Study

The goal of this clinical trial is to optimize treatment strategies for patients with p53-mutant oral epithelial dysplasia (OED) and early-stage oral squamous cell carcinoma (OSCC). The main question it aims to answer is what the most optimal treatment is at each diagnostic stage. It is hypothesized that lesions with p53-abnormal low-grade dysplasia (LGD) without surgical intervention will progress to high-grade dysplasia (HGD) or SCC in 4 years. It is also predicted that a clear p53 and severe/CIS excision margins in patients with p53-abnormal HGD will reduce the progression to invasive SCC, compared to clear severe/CIS margins, within 4 years. Finally, it is thought that patients with p53-abnormal cT1N0 and DOI<4mm receiving an END will have improved disease free and overall survival. This research will elucidate whether or not these hypotheses are correct.

Participants in each diagnostic cohort will be assigned to one of two different treatment options, listed below:

Cohort 1:

A) No intervention, observation only B) Surgical excision with clear margins

Cohort 2:

A) Surgical excision with clear severe/CIS margins B) Surgical excision with clear severe/CIS and p53 margins

Cohort 3:

A) Surgical excision and elective neck dissection (END) B) Surgical excision and close follow-up, only salvage ND if development of nodal disease

Inclusion Criteria:

• Adults age 18 or over
• No history of head and neck radiation
• p53-abnormal IHC patterns (surrogate marker for TP53 mutation)

Cohort 1:

• Biopsy-confirmed mild/moderate dysplasia

Cohort 2:

• Biopsy-confirmed severe dysplasia or CIS

Cohort 3:

• T1 SCC with depth of Invasion (DOI) <4mm
• Clinically and radiologically node-negative (confirmed by contrast-enhanced CT)

Exclusion Criteria:

• Immunocompromised status
• Lesions greater than 3 cm
• Presence of Proliferative Verrucous Leukoplakia

Cohort 1:

• Had prior treatment for oral premalignant lesions

Cohort 2:

• Presence of invasive SCC on initial biopsy

Cohort 3:

• Positive nodes on contrast-enhanced CT
• DOI >= 4mm