Evaluation of Two Non-Invasive Methods, High-Resolution Microendoscopy and Liquid-Based Cytology, for Detection of Oral Precancer

Summary

Cancers of the oral cavity (lip, oral tongue, gingivae, floor of mouth, hard palate, and other mouth tissues including buccal mucosa) are amongst the most common worldwide, with an estimated annual burden of over 300,000 incident cases. Most oral cancers (\>75%) are attributable to cigarette smoking, alcohol drinking, and chewing of areca nut/betel quid with or without tobacco, and very few are related to human papillomavirus infection. Oral cancer incidence geographically tracks with the prevalence of these risk factors and is notably high in the Indian subcontinent (due to tobacco chewing and smoking) and southeast Asia (due to betel quid chewing without tobacco and smoking).

The current standard for screening for oral precancer/cancer is visual and tactile examination by an expert for the presence of clinical/visual lesions (leukoplakia, erythroplakia, and oral submucous fibrosis). Such visually identified lesions are further triaged based on clinical impression for a biopsy to determine histopathologic presence/grade of dysplasia. Several observations point to key limitations of oral cancer screening based on clinical impression-based biopsy of visually identified lesions, including the decision to biopsy a lesion, which lesion to biopsy, and where within the lesion to direct a biopsy. Thus, there is a need for tools for improved triage of visual precancers for biopsy and targeting areas for biopsy within a lesion for more effective risk stratification and better provision of care.

Two non-invasive methods hold promise for triage of lesions for biopsy-oral liquid-based cytology and high-resolution microendoscopy (HRME). Oral cytology provides a method to non-invasively sample visible oral lesions and holds promise to enable triage of lesions for biopsy. HRME utilizes optical fiber-based imaging in combination with the fluorescent contrast agent proflavine to image sub-cellular features in vivo in lesions/epithelial tissues, functionally an in situ biopsy.

The investigators propose to conduct a cross-sectional study to evaluate the clinical utility of these two non-invasive methods for detecting oral precancer and early oral cavity cancer- the performance of oral cytology and HRME as an adjunct for triage of visible lesions for biopsy and the performance of HRME as an adjunct to enable better within-lesion targeting of areas for biopsy. If successful, this study would facilitate the development of a non-invasive, 3-step algorithm for oral cancer screening: identification of lesions through visual inspection, triage for biopsy through cytology or HRME, and targeted within-lesion biopsy (if needed) through HRME.

Conditions

• Oral Precancer
• Oral Cancer
• Oral Cancer Screening

Interventions

DEVICE

High-resolution microendoscopy of visible oral precancerous lesions

high-resolution images of nuclear morphometry within lesions will be obtained in vivo and displayed in real-time on a tablet. A handheld widefield imaging system will capture images with white light. Proflavine solution (0.01% w/v), a fluorescent antiseptic that stains cell nuclei, will be applied locally. The HRME will be placed in contact with each lesion and capture high resolution images from a 790 µm field of view. Optical markers will be calculated for each site imaged, and biopsy areas within lesion will be selected based on optical markers.

OTHER

Standard of care

Biopsy of ora precancer based on clinical assessment

Sponsors & Collaborators

• National Taiwan University Hospital

  collaborator OTHER

• Anil Chaturvedi

  lead NIH

Principal Investigators

• Anil Chaturvedi, PhD · Division of Cancer Epidemiology and Genetics, National Cancer Institute

• Philip Castle, PhD · Division of Cancer Epidemiology and Genetics, National Cancer Institute

• Cheng-Ping Wang, MD PhD · National Taiwan University Hospital

• Tseng-Cheng Chen · National Taiwan University Hospital

Study Design

Allocation

RANDOMIZED

Purpose

SCREENING

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

30 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-12-15

Primary Completion

2028-01-30

Completion

2029-01-30

Countries

• Taiwan