Oral PrecancerNCT07260344
Evaluation of Two Non-Invasive Methods, High-Resolution Microendoscopy and Liquid-Based Cytology, for Detection of Oral Precancer
A study testing High-resolution microendoscopy of visible oral precancerous lesions in people with Oral Precancer and Oral Cancer, run by Anil Chaturvedi at 1 site in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Oral Precancer, Oral Cancer, Oral Cancer Screening
- What is being tested?
- High-resolution microendoscopy of visible oral precancerous lesions
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 1 siteTaiwan
- Study dates
- 15 Dec 2025to 30 Jan 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Individuals aged 30-80 years
- Individuals with visible oral precancerous lesions of at 1 cm in greatest diameter
Who cannot join
- Individuals who are undergoing current cancer treatment or had a cancer within the last 12 months
- Individuals who are unwilling or unable to provide informed consent to participate
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Taiwan1 site, 1 recruiting
- Recruiting
National Taiwan University Hospital
Taipei, Taipei, 100
Cheng-Ping Wang, MD PhD, 886-(02)2312-3456 ext. 263155, wangcp@ntu.edu.tw
About this study
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.
Read more
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.
Read the detailed description
The investigators propose to conduct a cross-sectional randomized study to evaluate the performance of oral cytology and HRME (separately) versus clinical impression for triage of lesions for biopsy and the performance of HRME-directed biopsies versus clinician-directed biopsies. Performance will be evaluated based on yield of histopathologic disease- defined as diagnosis of any dysplasia (encompassing mild dysplasia, moderate dysplasia, severe dysplasia, or cancer) and high-grade disease (encompassing moderate dysplasia or above).
Upon identification of visible lesions, study investigators will ask the clinicians to provide a clinical impression regarding whether or not they would biopsy each lesion. Patients with visual oral precancer will then be randomized to one of two arms: 1) a standard-of-care clinical-directed biopsy arm or 2) HRME-directed biopsy arm. The biopsy decision in the clinical-biopsy arm will be guided by clinical impression/ examination under white light and the biopsy decision in the HRME-biopsy arm will be guided by HRME features. However, clinical impression and HRME features will be collected in both arms. Such availability of data will enhance the sample sizes for comparisons of clinical site of biopsy versus HRME site of biopsy.
The study specific aims are:
Aim 1: To evaluate the performance of oral cytology or HRME for triage of visually-identified lesions for biopsy. For cytology evaluation, this aim will combine participants from both arms and thus be non-randomized. For HRME evaluation, this aim will utilize participants from the HRME-directed biopsy arm. The yield of histopathologic disease will be compared between clinicians' response as to whether or not they would biopsy a lesion versus oral cytology or versus HRME.
Aim 2: To evaluate the performance of HRME for within-lesion targeting of regions for biopsy. This aim will be a randomized comparison of diagnostic yields of histopathologic disease between the clinician-directed biopsy arm versus the HRME-directed biopsy arm.
Combining both arms, different cut points (HRME scores range from 0-100) will be evaluated for the identification of any dysplasia or high-grade disease.
Aims 1 and 2 together will validate the performance of two non-invasive methods of diagnosing oral precancer. Cytology samples the entire lesion and could be a better representation of underlying disease status of the lesion when compared to visually-guided triage, while HRME allows better targeting of within-lesion areas for biopsy than visual impression.
Aim 3: To evaluate the within-lesion agreement between the area of clinician-directed biopsy and HRME-directed biopsy. This aim will combine participants from both arms and thus be non-randomized. This aim is anticipated to provide a potential explanation for why HRME does or does not improve the yield of disease when compared to clinical impression of within-lesion regions for biopsy.
Study design and procedures: This is a cross-sectional randomized study of 400 patients with visual oral precancer (leukoplakia, erythroplakia). Patients will be randomized (1:1 ratio) into 2 arms: 1) clinician-directed biopsy based on clinical examination/ impression or 2) HRME-directed biopsy based on HRME features.
Standard-of-care screening for visual oral precancer (through their national screening program) will be conducted by ENT clinicians through standard visual and tactile examination. Those eligible (defined as individuals ages 30-80 years with visible lesions with at least 1 cm in greatest diameter) will be approached and offered participation with informed consent.
Pre-randomization, all consenting participants will provide detailed demographic and behavioral information and will receive (in order) digital images of visible lesions, recording of whether or not the clinician would biopsy each lesion, recording of clinically-guided area of biopsy (regardless of clinician's decision to biopsy a lesion), and recording of HRME and HRME-guided area of biopsy. Participants will be randomized individually to one of the two study arms.
- In the clinician-directed biopsy arm, the clinician will take biopsy(s) from the predetermined location from the initial clinical assessment.
- In the HRME-directed biopsy arm, the clinician will take biopsies from lesion areas based on the prerecorded HRME reading.
Oral cytology will be collected after the HRME procedure to avoid tissue changes through cytology.
Study sites: The study would be conducted at the National Taiwan University Hospital (NTUH), Taipei.
- Conditions
- Oral Precancer, Oral Cancer, Oral Cancer Screening
- Being tested
- High-resolution microendoscopy of visible oral precancerous lesions, Standard of care
- Keywords
- oral cancer screening
- Medical subject headings
- Mouth Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-resolution microendoscopy of visible oral precancerous lesionsDevice
Also called Standard of care
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.
Standard of careOther
Biopsy of ora precancer based on clinical assessment
| Study group | Role | What they receive |
|---|---|---|
| Standard of care arm | Active comparator | Patients randomized to the standard of care arm will receive biopsy of visible oral precancer based on clinical assessment. Receives: Other: Standard of care |
| HRME arm | Experimental | Patients randomized to the HRME arm will receive biopsy of visible oral precancer based on high-resolution microendoscopy assessment. Receives: Device: High-resolution microendoscopy of visible oral precancerous lesions |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of oral dysplasia
Prevalence of any grade of dysplasia or high-grade dysplasia (moderate dysplasia, severe dysplasia, or cancer)
Measured: At study enrolment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2025
- Study start15 Dec 2025
- Primary completion30 Jan 2028 (estimated)
- Study completion30 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Oral PrecancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized individually to one of the two study arms. 1. In the clinician-directed biopsy arm, the clinician will take biopsy(s) from the predetermined location from the initial clinical assessment. 2. In the HRME-directed biopsy arm, the clinician will take biopsies from lesion areas based on the prerecorded HRME reading.
- Masking
- None (open label)
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Anil Chaturvedi
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Taiwan University Hospital
- Responsible party
- Sponsor-investigator, Anil Chaturvedi, National Institutes of Health Clinical Center (CC)
- Investigators
- Anil Chaturvedi, PhD, Principal investigator, Division of Cancer Epidemiology and Genetics, National Cancer InstitutePhilip Castle, PhD, Principal investigator, Division of Cancer Epidemiology and Genetics, National Cancer InstituteCheng-Ping Wang, MD PhD, Principal investigator, National Taiwan University HospitalTseng-Cheng Chen, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07260344
- Sponsor's protocol ID
- DCEG-SRP-2025-001
- Status last verified
- Nov 2025
- First submitted
- 1 Dec 2025
- Last updated
- 14 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified individual-level patient data will be shared by study investigators upon written request and review
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Two Non-Invasive Methods, High-Resolution Microendoscopy and Liquid-Based Cytology, for Detection of Oral Precancer
- ClinicalTrials.gov ID
- NCT07260344
- Acronym / sponsor ID
- DCEG-SRP-2025-001
- Conditions
- Oral Precancer, Oral Cancer, Oral Cancer Screening
- Keywords
- oral cancer screening
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Anil ChaturvediUS National Institutes of Health
- Collaborators
- National Taiwan University Hospital
- Study start
- 15 Dec 2025 (actual)
- Primary completion
- 30 Jan 2028 (estimated)
- Study completion
- 30 Jan 2029 (estimated)
- First posted
- 3 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The investigators propose to conduct a cross-sectional randomized study to evaluate the performance of oral cytology and HRME (separately) versus clinical impression for triage of lesions for biopsy and the performance of HRME-directed biopsies versus clinician-directed biopsies. Performance will be evaluated based on yield of histopathologic disease- defined as diagnosis of any dysplasia (encompassing mild dysplasia, moderate dysplasia, severe dysplasia, or cancer) and high-grade disease (encompassing moderate dysplasia or above).
Upon identification of visible lesions, study investigators will ask the clinicians to provide a clinical impression regarding whether or not they would biopsy each lesion. Patients with visual oral precancer will then be randomized to one of two arms: 1) a standard-of-care clinical-directed biopsy arm or 2) HRME-directed biopsy arm. The biopsy decision in the clinical-biopsy arm will be guided by clinical impression/ examination under white light and the biopsy decision in the HRME-biopsy arm will be guided by HRME features. However, clinical impression and HRME features will be collected in both arms. Such availability of data will enhance the sample sizes for comparisons of clinical site of biopsy versus HRME site of biopsy.
The study specific aims are:
Aim 1: To evaluate the performance of oral cytology or HRME for triage of visually-identified lesions for biopsy. For cytology evaluation, this aim will combine participants from both arms and thus be non-randomized. For HRME evaluation, this aim will utilize participants from the HRME-directed biopsy arm. The yield of histopathologic disease will be compared between clinicians' response as to whether or not they would biopsy a lesion versus oral cytology or versus HRME.
Aim 2: To evaluate the performance of HRME for within-lesion targeting of regions for biopsy. This aim will be a randomized comparison of diagnostic yields of histopathologic disease between the clinician-directed biopsy arm versus the HRME-directed biopsy arm.
Combining both arms, different cut points (HRME scores range from 0-100) will be evaluated for the identification of any dysplasia or high-grade disease.
Aims 1 and 2 together will validate the performance of two non-invasive methods of diagnosing oral precancer. Cytology samples the entire lesion and could be a better representation of underlying disease status of the lesion when compared to visually-guided triage, while HRME allows better targeting of within-lesion areas for biopsy than visual impression.
Aim 3: To evaluate the within-lesion agreement between the area of clinician-directed biopsy and HRME-directed biopsy. This aim will combine participants from both arms and thus be non-randomized. This aim is anticipated to provide a potential explanation for why HRME does or does not improve the yield of disease when compared to clinical impression of within-lesion regions for biopsy.
Study design and procedures: This is a cross-sectional randomized study of 400 patients with visual oral precancer (leukoplakia, erythroplakia). Patients will be randomized (1:1 ratio) into 2 arms: 1) clinician-directed biopsy based on clinical examination/ impression or 2) HRME-directed biopsy based on HRME features.
Standard-of-care screening for visual oral precancer (through their national screening program) will be conducted by ENT clinicians through standard visual and tactile examination. Those eligible (defined as individuals ages 30-80 years with visible lesions with at least 1 cm in greatest diameter) will be approached and offered participation with informed consent.
Pre-randomization, all consenting participants will provide detailed demographic and behavioral information and will receive (in order) digital images of visible lesions, recording of whether or not the clinician would biopsy each lesion, recording of clinically-guided area of biopsy (regardless of clinician's decision to biopsy a lesion), and recording of HRME and HRME-guided area of biopsy. Participants will be randomized individually to one of the two study arms.
- In the clinician-directed biopsy arm, the clinician will take biopsy(s) from the predetermined location from the initial clinical assessment.
- In the HRME-directed biopsy arm, the clinician will take biopsies from lesion areas based on the prerecorded HRME reading.
Oral cytology will be collected after the HRME procedure to avoid tissue changes through cytology.
Study sites: The study would be conducted at the National Taiwan University Hospital (NTUH), Taipei.
Study design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants will be randomized individually to one of the two study arms. 1. In the clinician-directed biopsy arm, the clinician will take biopsy(s) from the predetermined location from the initial clinical assessment. 2. In the HRME-directed biopsy arm, the clinician will take biopsies from lesion areas based on the prerecorded HRME reading.
| Arm | Type | Receives |
|---|---|---|
| Standard of care arm | Active comparator | Other: Standard of carePatients randomized to the standard of care arm will receive biopsy of visible oral precancer based on clinical assessment. |
| HRME arm | Experimental | Device: High-resolution microendoscopy of visible oral precancerous lesionsPatients randomized to the HRME arm will receive biopsy of visible oral precancer based on high-resolution microendoscopy assessment. |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Individuals aged 30-80 years
- Individuals with visible oral precancerous lesions of at 1 cm in greatest diameter
Key exclusion criteria (2 listed)
- Individuals who are undergoing current cancer treatment or had a cancer within the last 12 months
- Individuals who are unwilling or unable to provide informed consent to participate
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High-resolution microendoscopy of visible oral precancerous lesionsAlso: Standard of carehigh-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. | Device | HRME arm |
| Standard of careBiopsy of ora precancer based on clinical assessment | Other | Standard of care arm |
Primary outcome
Prevalence of oral dysplasia
Time frame: At study enrolment
Prevalence of any grade of dysplasia or high-grade dysplasia (moderate dysplasia, severe dysplasia, or cancer)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2026.
- Individual participant dataSharing planned: Yes. Deidentified individual-level patient data will be shared by study investigators upon written request and review
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Anil Chaturvedi, PhD principal investigator
Division of Cancer Epidemiology and Genetics, National Cancer Institute
Philip Castle, PhD principal investigator
Division of Cancer Epidemiology and Genetics, National Cancer Institute
Cheng-Ping Wang, MD PhD principal investigator
National Taiwan University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High-resolution microendoscopy of visible oral precancerous lesions in people with Oral Precancer and Oral Cancer, run by Anil Chaturvedi at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kelly Yu, PhD (240-276-7041, yuke@mail.nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevalence of oral dysplasia (time frame: At study enrolment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2026.