Diagnostic Accuracy of Salivary DNA Integrity Index in Oral Malignant and Premalignant Lesions

• ClinicalTrials.gov Identifier: NCT03682562
• Recruitment Status: Completed
• First Posted: September 24, 2018
• Last Update Posted: July 15, 2020
• Sponsor: Cairo University
• Information provided by (Responsible Party): Noha Adel Azab, Cairo University

Study Description

Brief Summary:

This study aims to identify the accuracy of DNA integrity index in differentiating between oral premalignant lesions and oral cancer.

Condition or disease	Intervention/treatment
Oral Cancer; Oral Lichen Planus; Oral Leukoplakia	Diagnostic Test: DNA Integrity Index

Detailed Description:

As stated by the U.S. Preventive Services Task Force and the National Institute of Dental and Craniofacial Research, the main screening test for oral cancer remains conventional oral examination of the oral cavity. Most cases of oral cancer are preceded by a clinically visible lesion. These lesions are called oral potentially malignant disorders. These are leukoplakia, erythroplakia, oral submucous fibrosis, oral lichen planus and discoid lupus erythematosis. Leukoplakia has a reported annual transformation rate of 2-3%, while OLP has a rate of 0.5% .

Full thickness tissue biopsy is the "gold standard" for diagnosing suspicious lesions should they be encountered during COE. However, oral biopsy is an invasive technique that can be challenging in sites as the floor of the mouth or the soft palate . The invasive nature of a biopsy also makes it unsuitable for cancer screening in high-risk populations.

Thus there is a need for a diagnostic aid that can help primary care providers determine which patients need to be biopsied or referred to a specialist.

Nucleic acids can be released actively or passively into the circulation by both living and dead cells, where the latter is considered the predominant source. Programmed cell death gives neatly digested DNA fragments of approximately 180 bp in length. In case of solid tumors, cell-free DNA is released through necrosis which generates longer DNA fragments due to haphazard and incomplete digestion of DNA. Thus, the integrity of the DNA fragment can determine its origin making DNA integrity a potential marker for oral cancer.

The DNA integrity index (DII) is the ratio between the longer DNA fragments to the shorter ones. A higher index has been reported in breast, prostate, liver and cervical cancer. Jiang et al. 2006 found that the DNA integrity index was significantly higher in oral cancer patients than in normal ones and reported a sensitivity and specificity values of 84.5% 83% respectively . The next step for such a marker would be early quantification of performance in clinical settings to determine if it is possible to extrapolate cut off values.

Study Design

• Study Type: Observational
• Actual Enrollment: 93 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Diagnostic Accuracy of Salivary DNA Integrity Index in Oral Malignant and Premalignant Lesions
• Actual Study Start Date: September 15, 2019
• Actual Primary Completion Date: March 10, 2020
• Actual Study Completion Date: March 10, 2020

Groups and Cohorts

Group/Cohort	Intervention/treatment
Oral Cancer; Patients diagnosed clinically and histopathologically as having oral cancer.	Diagnostic Test: DNA Integrity Index; This test will be performed for ALL three groups: Sample collection: Patients will be given a sterile cup containing 5mL saline solution with which they will vigorously rinse their mouth while rubbing their tongues against the oral mucosa for 30 seconds, then spit it back into the cup. The solution will then be used for DNA extraction. DNA integrity analysis: The DNA integrity will be done through measuring a housekeeping gene using competitive polymerase chain reaction where the isolated DNA will be combined with DNA capture probes for sequence-specific DNA fragments. The DNA integrity index will be calculated as the ratio of the concentration of longer DNA fragments to the ratio of shorter ones.
Premalignant Oral Lesions; Patients diagnosed clinically and histopathologically with either leukoplakia or oral lichen planus as stated by modified WHO criteria	Diagnostic Test: DNA Integrity Index; This test will be performed for ALL three groups: Sample collection: Patients will be given a sterile cup containing 5mL saline solution with which they will vigorously rinse their mouth while rubbing their tongues against the oral mucosa for 30 seconds, then spit it back into the cup. The solution will then be used for DNA extraction. DNA integrity analysis: The DNA integrity will be done through measuring a housekeeping gene using competitive polymerase chain reaction where the isolated DNA will be combined with DNA capture probes for sequence-specific DNA fragments. The DNA integrity index will be calculated as the ratio of the concentration of longer DNA fragments to the ratio of shorter ones.
Normal Subjects; Patients who give a history of: No smoking; No alcohol; No systemic disease; and who on conventional oral examination have:; No visible oral lesions on conventional oral examination .; Good oral hygiene.	Diagnostic Test: DNA Integrity Index; This test will be performed for ALL three groups: Sample collection: Patients will be given a sterile cup containing 5mL saline solution with which they will vigorously rinse their mouth while rubbing their tongues against the oral mucosa for 30 seconds, then spit it back into the cup. The solution will then be used for DNA extraction. DNA integrity analysis: The DNA integrity will be done through measuring a housekeeping gene using competitive polymerase chain reaction where the isolated DNA will be combined with DNA capture probes for sequence-specific DNA fragments. The DNA integrity index will be calculated as the ratio of the concentration of longer DNA fragments to the ratio of shorter ones.

Outcome Measures

Primary Outcome Measures :

1. Difference in DNA Integrity Index [ Time Frame: 1 month after the end of patient recruitment ]
   The DNA integrity will be compared between the three group to determine whether there is a difference between them in that aspect or not

Biospecimen Retention:   Samples With DNA

Salivary Samples will be obtained for DNA extraction, Biosamples will be stored in -80 degrees after patient's consent

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Sampling Method: Non-Probability Sample

Study Population

Group I: (Clinical examination and Biopsy) Patients diagnosed clinically and histopathologically as having oral cancer. Group II: (History and Clinical examination)

Patients who give a history of:

• No smoking
• No alcohol
• No systemic disease; and who on conventional oral examination(National Institute of Dental and Craniofacial Research, 2013b) have:
• No visible oral lesions on conventional oral examination .
• Good oral hygiene. Group III: (Clinical examination and Biopsy) Patients diagnosed clinically and histopathologically with oral lichen planus as stated by modified WHO criteria (van der Meij and van der Waal, 2003).

Criteria

Patients in this study will be divided into three groups:

Group I: Patients diagnosed histopathologically with oral cancer recruited from the National Cancer Institute, who have yet to receive treatment.

Group II: Healthy Controls

Inclusion Criteria:

• No visible oral lesions as detected by conventional oral examination
• Good oral hygiene, with healthy gingival tissues
• Non-smokers
• No systemic disease Group III: Patients diagnosed with oral lichen planus according to the modified WHO (van der Meij and van der Waal, 2003)diagnostic criteria not receiving treatment at least 8 weeks prior to enrollment.

Contacts and Locations

Locations

Egypt

Faculty of Dentistry - Cairo University

Cairo, Egypt, 11553

Sponsors and Collaborators

Cairo University

More Information

• Responsible Party: Noha Adel Azab, Researcher, Cairo University
• ClinicalTrials.gov Identifier: NCT03682562
• Other Study ID Numbers: N1P1H1D1
• First Posted: September 24, 2018
• Last Update Posted: July 15, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: According to the mode of data entry, if it is solely numerical it can be more easily shared and deposited on repositories, however patient clinical photos may not be possible to share

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Mouth Neoplasms; Precancerous Conditions; Leukoplakia; Leukoplakia, Oral; Lichen Planus, Oral; Lichen Planus; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases; Lichenoid Eruptions; Skin Diseases, Papulosquamous; Skin Diseases; Pathological Conditions, Anatomical