Providing clinicians with more accurate and objective data to help them determine treatment options for their patients with oral lesions

Straticyte™ is a novel prognostic tool developed by Proteocyte AI that can provide, as a complement to histopathology, an individual personalized assessment of the 5-year risk for an oral lesion to progress from a precancerous lesion to an invasive squamous cell cancer. By categorizing oral lesions more accurately than the current histological dysplasia grading, Straticyte enables better patient care as more effective follow-up regimens can be developed for individual patients.

Oral Lesions:

Lichen Planus

  • Common muco-cutaneous disorder
  • Multiple presentations
  • Malignant potential controversial, erosive form has been suggested
  • If real, less than 2% develop malignancy over a 10 year period
  • Necessary to distinguish from lichenoid dysplasia
Leukoplakia

  • White plaque that cannot be scraped off, cannot be given another specific diagnosis and has no known etiology (except tobacco use)
  • 7 to 15% show dysplasia or malignancy at biopsy
  • Varying patterns, granular, verruciform, thick, thin
Erythroleukoplakia

  • Variable likelihood of malignancy or premalignancy
  • > red = > likelihood
  • > white = < likelihood
Erythroplakia

  • Clinical term, red macule which does not rub off and is not explained by any other process
  • >80% show malignancy or significant dysplasia at biopsy
Actinic Cheilitis

  • Effect of direct exposure to sunlight over a prolonged period of time
  • Lower lip>>>upper lip
  • Common in outdoor workers, sun soakers
  • Deceptively benign in appearance, both clinically and histologically
Sublingual Keratosis

  • Uncommon variant of “leukoplakia”
  • Well-demarcated, thick white patch on ventral tongue, floor of mouth
  • Initial biopsy often benign
  • High incidence of carcinoma
  • Recommended treatment – excision
Proliferative Verrucous Leukoplakia (PVL)

  • First described – 1985 RARE
  • White plaque with nodular, papillary or verruciform surface
  • Spreads rapidly
  • Females>>>males
  • Age range ~20-80
  • Buccal mucosa and tongue most affected
  • 70% will develop a ca within a decade following diagnosis.
  • Aggressive surgical treatment
Stomatitis in Reverse Smokers

  • Lit end in the mouth
  • Common practice in parts of India, South America and the Philippines.
  • Largely older women
  • Differs from nicotinic stomatitis
  • Accounts for ~ 50% of malignancies in some parts of the world

%

Straticyte was able to reclassify 65% of mild dysplasia cases into a higher risk category. These reclassified cases are 2.5 times more likely to progress to cancer within 5 years than the other mild dysplasia cases.

Clinical Need

Clinicians can identify cancer-prone lesions before these lesions become tumours

Oral cancer affects 450,000 people/year worldwide, with a 5-year mortality rate of approximately 47% in the United States and 50% worldwide, predominantly due to late diagnosis. Late stage cancers are more costly and difficult to treat. In the United States, treatment of oral cancer in the first year costs on average $79,000 per patient. However, early stage diagnosis of localized disease significantly lowers the mortality rate, to 17%, and the treatment costs by up to $50,000 per patient.

Our current understanding of oral cancer development is of a step-wise cellular progression from normal to premalignant and then to invasive carcinoma. Oral Premalignant Lesions are quite common, are frequently asymptomatic, occurring in around 2.5% of the population, and are generally detected during a routine intraoral exam. While the transformation rate of precancerous lesion to cancerous lesions is less than 5% per year, most early stage cancers and premalignant lesions are also asymptomatic, making identification more difficult. Most premalignant lesions do not require aggressive treatment; however, preventing the transformation to malignancy is key to impacting oral cancer morbidity and mortality. For effective treatment, clinicians must first identify these often asymptomatic precancerous lesions and then develop a management plan prior to their transformation to malignant lesions.

The high mortality rate associated with oral cancer and the low transformation rate of premalignant lesions (≈1 in 20) creates a strong need for a reliable way to more accurately identify lesions at high risk of transformation, separating these lesions from those at lesser transformation risk. Straticyte has been developed to meet this need.

The standard of care for oral premalignant lesion risk assessment is dysplasia grading by histopathology. Historically, histopathology is impacted by intra- and inter-observer variation as well as significant overlap between grades, affecting its usefulness as a prognostic tool. In particular, for mild and moderate dysplasias, grading does not provide clinicians with the prognostic information, including risk for progression, to allow them to categorize their patient’s cancer risk. Further data is needed for these lower grade lesions as a certain percentage of mild dysplastic lesions are associated with significant transformation risk, while a percentage of moderate dysplastic lesions are associated with a wide prognostic range which overlaps both mild and severe dysplasia.

The limitations with the current standard of care have led to a widely recognized urgent need for more effective prognostic biomarkers for oral premalignant lesions amongst the clinicians who treat oral cancer.

Figure 1. Oral dysplasia: Straticyte sample quantitation by Image Analysis (1A, immunohistochemistry; 1B, labelled biomarker locations)

 

Straticyte Retrospective Clinical Data

Straticyte was developed utilizing retrospective clinical data (168 dysplasia cases and 427 cancer cases). The company is committed to enriching its dataset with retrospective cohorts. Proteocyte AI is currently initiating several retrospective studies with major Canadian oral pathology centres.

Straticyte™

Straticyte is a novel prognostic tool which provides an individual, personalized, quantitative risk score for an oral premalignant lesion to progress to a cancerous lesion within 5 years. Using biomarkers, Straticyte provides additional and more accurate information about an oral lesion compared to what histopathology alone offers.

Straticyte better defines the patient’s risk for developing oral cancer by separating the lesions into risk categories (low, medium, or high) with very little overlap. A low Straticyte score signifies that the risk for progression to cancer is <19% over 5 years (<4% /year). Straticyte classifies many lesions identified by histopathology with moderate dysplasia (and uncertain risk for progression) into the low or high risk categories. With a more accurate understanding of a patient’s risk, a clinician can more confidently determine treatment plans for the patient.

The protein S100A7, along with other candidate biomarkers for oral pharyngeal early neoplasia, was discovered by researchers at York University and Mount Sinai Hospital in Toronto, Canada through proteomic studies in head and neck cancer. S100A7 was found to be an excellent prognostic marker for cancer progression in mucosal oral premalignant lesions (dysplasia). Straticyte uses S100A7 immunohistochemistry on adjacent slides cut from the same biopsy sample used for standard histopathology (Sample image below). No additional biopsy material is needed.

Within the sample, S100A7-positive cells are quantified and combined, via proprietary algorithms, to produce an index number. This index number is converted into a risk score following a comparison with Proteocyte AI’s eference database (containing >150 annotated oral dysplasia cases with 5-year outcomes). The resultant risk score is reported as the individual probability of cancer occurrence within 5 years and a risk category (low, medium, or high). Proteocyte AI is continuously expanding its reference database through retrospective clinical studies.