Oral Epithelial Dysplasia, Mild or Moderate Grade
Conditions
Keywords
oral epithelial dysplasia, p16 methylation, prognosis, malignant transformation, oral squamous cell carcinoma
Brief summary
Oral epithelial dysplasia (OED) is one of the common precancerous lesions among Chinese adults. Biomarker is not available for detection of malignant potential of OED till now. p16 is an important tumor suppressor gene, which is inactivated frequently by methylation of CpG island in early stage of carcinogenesis. The present cohort study is to investigate whether p16 methylation is correlated with malignant transformation of OED.
Detailed description
* Background: Identification of malignant potential of oral epithelial dysplasia (OED) is virtually impossible on histopathological grounds alone. Inactivation of p16 gene by CpG methylation is an early frequent event during oral carcinogenesis. To investigate the predictive value of p16 methylation on malignant potential in OED, we carried out the prospective cohort study. * Methods: 101 patients with histologically confirmed mild or moderate OED were included in the present study. Baseline information of p16 methylation status of the OED lesions from 93 cases was obtained by methylation-specific PCR. Progression of the OEDs lesions was examined in 78 cases histologically during the 45.8 months double-blind followup survey (78/93). The association between p16 methylation and progression of OED was analyzed with SPSS13.0 software. All P-values were two-sided.
Interventions
None listed
Sponsors
Peking University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* histological diagnosis of mild or moderate grade OED; and * enough amount of tissue sample from OED lesion for genomic DNA extraction; and * available of methylation status of p16 CpG island in the extracted DNA sample.
Exclusion criteria
* histological diagnosis of severe grade OED or malignant disease; or * amount of tissue sample is not enough for preparation of genomic DNA (20ng); or * quality of the prepared DNA is not good enough for detection of p16 methylation; or * OED treatment history by LASER, radiotherapy, or chemotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With Both Clinical and Histological Evidence of Malignant Transformation of Oral Epithelial Dysplasia | from 3 months to 124 months | The follow-up examination was carried out with a 3-month interval. Re-biopsy was done as clinically indicated, e.g. the lesion recurs or has tendency for malignant development. Pathologic diagnosis was made by at least two pathologists without the knowledge of baseline p16 methylation, based on the World Health Organization's criteria, at Peking University School of Stomatology. The number of participants with malignant transformation of oral dysplasia was calculated based on the number of participants with oral dysplasia progressed to carcinoma by the end of the trial in each cohorts. |
Secondary
| Measure | Time frame |
|---|---|
| Cancer-free Survival Time for Patients With Oral Epithelial Dysplasia | from 3 months to 124 months |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| p16-methylated patients with mild or moderate oral epithelial dysplasia containing methylated p16 CpG island. | 35 |
| p16-unmethylated patients with mild or moderate oral epithelial dysplasia NOT containing methylated p16 CpG island. | 58 |
| Total | 93 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 12 |
Baseline characteristics
| Characteristic | Total | p16-methylated | p16-unmethylated |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 31 Participants | 12 Participants | 19 Participants |
| Age, Categorical Between 18 and 65 years | 62 Participants | 23 Participants | 39 Participants |
| Age, Continuous | 57.7 years STANDARD_DEVIATION 11.3 | 57.5 years STANDARD_DEVIATION 12 | 57.9 years STANDARD_DEVIATION 11 |
| Region of Enrollment China | 93 participants | 35 participants | 58 participants |
| Sex: Female, Male Female | 57 Participants | 21 Participants | 36 Participants |
| Sex: Female, Male Male | 36 Participants | 14 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 35 | 0 / 58 |
| serious Total, serious adverse events | 0 / 35 | 0 / 58 |
Outcome results
Primary
The Number of Participants With Both Clinical and Histological Evidence of Malignant Transformation of Oral Epithelial Dysplasia
The follow-up examination was carried out with a 3-month interval. Re-biopsy was done as clinically indicated, e.g. the lesion recurs or has tendency for malignant development. Pathologic diagnosis was made by at least two pathologists without the knowledge of baseline p16 methylation, based on the World Health Organization's criteria, at Peking University School of Stomatology. The number of participants with malignant transformation of oral dysplasia was calculated based on the number of participants with oral dysplasia progressed to carcinoma by the end of the trial in each cohorts.
Time frame: from 3 months to 124 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| p16-methylated | The Number of Participants With Both Clinical and Histological Evidence of Malignant Transformation of Oral Epithelial Dysplasia | 32 participants |
| p16-unmethylated | The Number of Participants With Both Clinical and Histological Evidence of Malignant Transformation of Oral Epithelial Dysplasia | 46 participants |
Secondary
Cancer-free Survival Time for Patients With Oral Epithelial Dysplasia
Time frame: from 3 months to 124 months