Prevalence of human papillomavirus in oral cancer in Asia: A systematic review and meta-analysis.

OBJECTIVE: To determine the prevalence of human papillomavirus (HPV) in oral squamous cell carcinoma (OSCC) across Asian countries, focusing on South and Southeast Asia. METHODS: A systematic search of four databases-MEDLINE/PubMed, EMBASE, Scopus, and ProQuest-was conducted to identify observational studies published between January 2013 and December 2023. The pooled prevalence of HPV was estimated using random-effects models, and subgroup analysis was performed to investigate the source of heterogeneity. RESULTS: A total of 77 studies were included, comprising 7289 OSCC cases from 11 countries. The pooled HPV prevalence in OSCC was 23.1% (95% CI 17.9-28.7, I2 = 96.7%). South Asia had the highest prevalence (27.1%), followed by East Asia (19.4%), and Southeast Asia (16.7%). Two subtypes were commonly reported: HPV-16 (9.1%) and HPV-18 (5.1%). Anatomical subsites, buccal mucosa (34.0%), and floor of the mouth (33.2%) had similar ranges of HPV prevalence. All studies exhibited a high degree of heterogeneity, with the OSCC location and risk of bias identified as potential sources of heterogeneity. CONCLUSIONS: Due to the high HPV prevalence in OSCC in Asia, HPV detection in routine pathology practice is recommended. Future studies should be conducted in multicentre settings using similar HPV detection methods and reporting detailed demographic and clinical information on oral sub-sites.

Expression of CLLD7 and CHC1L Proteins in Oral Epithelial Dysplasia in a Group of Thai Patients.

OBJECTIVES: Previous study showed aberrant CLLD7 and CHC1L protein expression in oral squamous cell carcinoma (OSCC) compared to normal oral mucosa (NOM). This study aimed to evaluate the expression of these proteins in oral epithelial dysplasia (OED). MATERIALS AND METHODS: Forty specimens of OED and 11 NOM were used. The expression of CLLD7 and CHC1L was determined by immunohistochemistry. In each case, at least 1000 cells were counted. Presence of nuclear, cytoplasmic, and/or membrane staining of CLLD7 and CHC1L were considered positive. Percentages of total positive cells and positive cells at different locations were recorded. SPSS version 18 was used to compare variation between groups with statistical significance at p<0.05. RESULTS: No significant differences in the percentages of total positive cells of CLLD7 and CHC1L were found between NOM and all grades of OED. Nevertheless, there were significant differences in subcellular staining of these two proteins. In CLLD7, the nuclear staining of the moderate and the severe OED groups was significantly lower than that of the NOM group (p<0.05). The percentages of membrane staining of CHC1L in moderate and severe OED were significantly higher than that of NOM (p<0.001). In addition, the nuclear staining of CHC1L in each grade of OED was significantly lower than that of NOM (p<0.05). CONCLUSION: The subcellular mislocalization of CLLD7 and CHC1L in OED suggests that the expression of these potential tumor suppressor proteins might be dysregulated during the dysplastic process. The distinct membrane staining of CHC1L observed in OED but not in NOM is a useful characteristic that can be used to separate OED from NOM. Thus, CHC1L may be a good marker to assist in the diagnosis of OED.

Detection of high-risk HPV 16 genotypes in cervical cancers using isothermal DNA amplification with electrochemical genosensor.

Cervical cancer emerges as the third most prevalent types of malignancy among women on a global scale. Cervical cancer is significantly associated with the persistent infection of human papillomavirus (HPV) type 16. The process of diagnosing is crucial in order to prevent the progression of a condition into a malignant state. The early detection of cervical cancer through initial stage screening is of the utmost significance in both the prevention and effective management of this disease. The present detection methodology is dependent on quantitative polymerase chain reaction (qPCR), which necessitates the use of a costly heat cycler instrument. In this study, we report the development of an electrochemical DNA biosensor integrated with an isothermal recombinase polymerase amplification (RPA) reaction for the detection and identification of the high-risk HPV-16 genotype. The electrochemical biosensor exhibited a high degree of specificity and sensitivity, as evidenced by its limit of detection (LOD) of 0.23 copies/µL of HPV-16 DNA. The validity of this electrochemical platform was confirmed through the analysis of 40 cervical tissues samples, and the findings were consistent with those obtained through polymerase chain reaction (PCR) testing. Our straightforward electrochemical detection technology and quick turnaround time at 75 min make the assay suitable for point-of-care testing in low-resource settings.

The development of an online serious game for oral diagnosis and treatment planning: evaluation of knowledge acquisition and retention.

BACKGROUND: While serious games seem to be supportive in healthcare education, none of them had been designed to develop competence in diagnosis and treatment planning of oral lesions. Therefore, this research aimed to develop an online simulation-based serious game for training diagnosis and treatment planning of oral lesions (SimOL) and to evaluate its educational impact in terms of knowledge improvement and retention. METHODS: As a mandatory task in an oral lesion course, all 28 students were required to participate in SimOL activities. Participants were instructed to complete a pre-knowledge assessment following a one-week washout period prior to the game activity. Subsequent to the game completion, they were tasked to complete a post-knowledge assessment I (Full score = 15) and satisfaction questionnaire. A post-knowledge assessment II was administered a week later to evaluate knowledge retention. RESULTS: The findings demonstrated a significant increase in the assessment scores after interacting with the game (P < 0.001), where the pre- and immediate post-knowledge assessment scores were 8.00 (SD = 2.11) and 11.71 (SD = 2.39), respectively. The game also exhibited a positive impact on knowledge retention, as there was no significant difference between the scores of post-knowledge assessment I and II (P > 0.05). Additionally, students perceived the game as positively in all aspects, although the entertainment aspect achieved a slightly lower score of 3.70 (SD = 0.21), in comparison to the usefulness and ease of use with a score of 4.02 (SD = 0.11) and 4.02 (SD = 0.16), respectively. CONCLUSION: SimOL demonstrated its potential as an effective learning tool for improving and retaining knowledge for diagnosis and treatment planning of oral lesions. The game was perceived positively by dental students in all aspects, however further improvements should prioritize the enhancement of entertaining components.

Oral mucous membrane pemphigoid in a group of Thai patients-A 15-year retrospective study.

Background/purpose: Mucous membrane pemphigoid (MMP) is a rare autoimmune disease affecting mucous membrane of the body. Oral involvement is common causing chronic and painful lesions. This study aimed to characterize oral MMP in a group of Thai patients and to analyze treatment regimens. Materials and methods: The files of patients attending Oral Medicine Clinic were retrospectively studied. Patients fulfilled diagnostic criteria of MMP were included. Chief complaints, medical and dental history, oral manifestations and investigations of individual patients were summarized. Treatment regimens and efficacy were also analyzed. Results: There were fourteen patients (age range 33-70 years) with a diagnosis of MMP. The prevalence of oral MMP was 0.51%. The lesions presented as vesicles, blood blisters, erosions, ulcers, erythema, either one type or in combination. Common complaints were chronic painful and bleeding gums. Gingival lesions were found in 13 of 14 patients (92.86%). The most common direct immunofluorescence findings were linear C3 at basement membrane zone (92.31%) followed by linear IgG deposition (84.62%). Most lesions were successfully managed with topical and/or systemic corticosteroids. The average time to control disease was 1.97 months (IQR, 0.69-12.73 months). Conclusion: Gingival lesions are very common in MMP. Mainstay of treatment is combination of systemic and topical corticosteroids. Multidisciplinary care including oral hygiene maintenance is necessary.

A Multianalyte Electrochemical Genosensor for the Detection of High-Risk HPV Genotypes in Oral and Cervical Cancers.

Infection with high-risk human papillomavirus (HPV) is a major risk factor for oral and cervical cancers. Hence, we developed a multianalyte electrochemical DNA biosensor that could be used for both oral and cervical samples to detect the high-risk HPV genotypes 16 and 18. The assay involves the sandwich hybridization of the HPV target to the silica-redox dye reporter probe and capture probe, followed by electrochemical detection. The sensor was found to be highly specific and sensitive, with a detection limit of 22 fM for HPV-16 and 20 fM for HPV-18, between the range of 1 fM and 1 µM. Evaluation with oral and cervical samples showed that the biosensor result was consistent with the nested PCR/gel electrophoresis detection. The biosensor assay could be completed within 90 min. Due to its simplicity, rapidity, and high sensitivity, this biosensor could be used as an alternative method for HPV detection in clinical laboratories as well as for epidemiological studies.

Potential Role of Epstein-Barr Virus in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma: A Scoping Review.

Though the oral cavity is anatomically proximate to the nasal cavity and acts as a key reservoir of EBV habitation and transmission, it is still unclear whether EBV plays a significant role in oral carcinogenesis. Many studies have detected EBV DNA in tissues and exfoliated cells from OSCC patients. However, very few studies have investigated the expression of functional EBV proteins implicated in its oncogenicity. The most studied are latent membrane protein 1 (LMP-1), a protein associated with the activation of signalling pathways; EBV determined nuclear antigen (EBNA)-1, a protein involved in the regulation of gene expression; and EBV-encoded small non-polyadenylated RNA (EBER)-2. LMP-1 is considered the major oncoprotein, and overexpression of LMP-1 observed in OSCC indicates that this molecule might play a significant role in oral carcinogenesis. Although numerous studies have detected EBV DNA and proteins from OSCC and oral potentially malignant disorders, heterogeneity in methodologies has led to discrepant results, hindering interpretation. Elucidating the exact functions of EBV and its proteins when expressed is vital in establishing the role of viruses in oral oncogenesis. This review summarises the current evidence on the potential role of EBV in oral oncogenesis and discusses the implications as well as recommendations for future research.

Overexpression of Epstein-Barr virus-encoded latent membrane protein-1 (LMP-1) in oral squamous cell carcinoma.

BACKGROUND: As oral cavity is the main location of Epstein-Barr virus (EBV) latency and shedding, and as EBV-encoded latent membrane protein-1 (LMP-1) has a crucial role in cell transformation, association between EBV infection, LMP-1 expression and oral malignancy is of interest. Although EBV DNA has been detected in oral squamous cell carcinoma (OSCC), studies on LMP-1 expression in OSCC and oral potentially malignant disorders are scarce and still controversial. This study aimed to evaluate the expression of LMP-1 in OSCC and oral leukoplakia (OL). METHODS: Biopsy specimens of 36 OSCC, 69 OL with and without dysplasia and 10 normal oral mucosa were assessed for the expression of LMP-1 using immunohistochemistry. In each case, at least 1000 cells were counted. Cells with staining were considered positive, classified by location as nuclear, cytoplasmic and nuclear plus cytoplasmic staining. Percentage of positive cells at different locations and of total positive cells were determined. For statistical analysis, SPSS version 21 was used. Statistical significance was considered at p < 0.05. RESULTS: LMP-1 was expressed in all studied specimens. In terms of percentage of total positive cells, LMP-1 expression was higher from normal mucosa (26.36%), OL without dysplasia (28.03%), OL with dysplasia (34.15%), to the significantly highest, (59.67%) in OSCC. In addition, cells with nuclear staining alone, cytoplasmic staining alone and cells with nuclear plus cytoplasmic staining were significantly higher in OSCC compared to those of normal mucosa, OL with and without dysplasia. CONCLUSIONS: LMP-1 was overexpressed in OSCC. Our analysis on subcellular localization of LMP-1 in OSCC revealed prominent distinguished pattern, cytoplasmic distribution. Further studies in cell lines and animals are required to clarify the association between this EBV-encoded proteins and oral carcinogenesis.

Putative salivary protein biomarkers for the diagnosis of oral lichen planus: a case-control study.

BACKGROUND: Salivary protein biomarkers for screening and diagnosis of oral lichen planus (OLP) are not well-defined. The objective of this study was to identify putative protein biomarkers for OLP using proteomic approaches. METHODS: Pooled unstimulated whole saliva was collected from five OLP patients and five healthy control participants. Saliva samples were then subjected to two-dimensional gel electrophoresis, followed by mass spectrometry to identify putative protein biomarkers. Subsequently, a subset of these putative biomarkers were validated in 24 OLP patients and 24 age-matched healthy control subjects, using an enzyme-linked immunosorbent assay (ELISA). Immunoblotting analyses were then performed in 3 pairs of age- and sex-matched OLP patients and healthy controls to confirm results from the ELISA study. RESULTS: Thirty-one protein spots were identified, corresponding to 20 unique proteins. Notably, fibrinogen fragment D and complement component C3c exhibited increased expression in OLP patients, while cystatin SA exhibited decreased expression in OLP patients, compared with healthy control subjects. ELISA analyses indicated increased expression of fibrinogen fragment D and complement component C3c, and decreased expression of cystatin SA, in the saliva of OLP patients. Statistical differences in the expression of salivary complement C3c were observed between OLP patients and healthy control subjects. Immunoblotting analyses confirmed the results of our ELISA study. CONCLUSION: Complement C3c, fibrinogen fragment D and cystatin SA may serve as salivary biomarkers for screening and/or diagnosis of OLP.

Direct Immunofluorescence in Oral Lichen Planus.

INTRODUCTION: Oral lichen planus (OLP) is a common immune-mediated oral mucosal disease. Diagnosis of OLP depends mainly on both clinical and histopathological features. Direct immunofluorescence (DIF) is a useful investigation method to distinguish between similar lesions and to confirm diagnosis in cases of uncharacterized features. AIM: The purpose of this study was to evaluate the prevalence and pattern of DIF in a group of Thai patients with OLP. MATERIALS AND METHODS: Records of clinically and histologically diagnosed OLP patients attending the Oral Medicine Clinic, Faculty of Dentistry, Mahidol University, Bangkok, Thailand were consecutively reviewed for DIF results. The DIF patterns in these patients were analysed. RESULTS: There were 82 atrophic and/or erosive OLP patients with a mean age of 51.6 years. Male to female ratio was 1:5. Of these, 82.9% showed positive DIF. Buccal mucosa was superior to the gingiva and palate in terms of sensitivity for DIF. All specimens except one (98.5%) demonstrated deposition of fibrinogen at the basement membrane zone (BMZ) in a shaggy pattern. The most common DIF pattern was shaggy fibrinogen at BMZ with IgM deposition on the colloid bodies (CB) (35.3%) followed by shaggy fibrinogen along BMZ (27.9%). CONCLUSION: The prevalence of positive DIF in Thai OLP patients was 82.9%. The most common finding was shaggy fibrinogen at BMZ. The typical pattern was shaggy fibrinogen along BMZ with or without positive IgM at CB. DIF pattern could be evaluated for the diagnosis of OLP lacking clinical and/or histopathological characteristic features.

Knowledge of human papillomavirus and its association with head and neck benign and malignant lesions in a group of dental patients in pakistan.

Human papillomaviruses (HPVs) remain a serious world health problem due to their association with cervical and head and neck cancers. While over 100 HPV types have been identified, only a few subtypes are associated with malignancies. HPV 16 and 18 are the most prevalent oncogenic types in head and neck cancers. Although it has been proven that some subsets of benign and malignant head and neck lesions are associated with HPV, the general population have very little awareness and knowledge of their association with HPV. Therefore, the purpose of this study was to determine the knowledge of HPV and its links with head and neck benign and malignant lesions in a group of Pakistani dental patients who attended the Dental Department of the Sandeman provincial hospital in Quetta, Pakistan. One hundred and ninety-two patients were recruited and requested to answer a questionnaire. It was revealed that there was a low level of knowledge about HPV and its association with head and neck benign and malignant lesions among the participants. This result suggested that more education regarding the relationship of HPV in inducing head and neck benign and malignant lesions is required in this group of patients.

Detection of human papillomavirus in normal oral cavity in a group of Pakistani subjects using real-time PCR.

Since there is evidence that human papillomavirus (HPV) may play some role in oral carcinogenesis, we investigated the presence of HPV in a group of Pakistani subjects with normal oral cavity using real-time PCR analysis. Two-hundred patients attending the Dental Department, Sandaman Provincial Hospital, Balochistan, Pakistan, were recruited. After interview, oral epithelial cells were collected by scraping and subjected to DNA extraction. The HPV-positive DNA samples were further analyzed using primer sets specific for HPV-16 and -18. It was found that out of 200 DNA samples, 192 were PCR-positive for the ß-globin gene and these were subsequently examined for the presence of HPV DNA. Among these, 47 (24.5%) were HPV-positive with the virus copy number ranged between 0.43-32 copies per 1 µg of total DNA (9-99 copies per PCR reaction). There were 4 and 11 samples containing HPV-16 and -18, respectively. Additionally, one sample harbored both types of HPV. Among the investigated clinical parameters, smoking habit was associated with the presence of HPV (p=0.001) while others indicated no significant association. The prevalence of HPV in normal oral cavity in our Pakistani subjects appears to be comparable to other studies. However, the association between the presence of HPV and smoking warrants further investigations whether both of these factors can cooperate in inducing oral cancer in this group of patients.

In vitro antifungal activities of longan (Dimocarpus longan Lour.) seed extract.

Longan, Dimocarpus longan Lour., contains polyphenolic compounds which exhibit several pharmacological properties. This study aims to evaluate antifungal activities of longan fruit extract in comparison to its active compounds. The results showed that longan seed exhibited antifungal activity against the opportunistic yeasts (Candida species and Cryptococcus neoformans). In contrast, longan pulp and whole fruit did not demonstrate any inhibitory effects. Ellagic acid showed the most potent antifungal activity followed by corilagin and gallic acid, respectively. Ellagic acid inhibited Candida parapsilosis and C. neoformans more effectively than Candida krusei and also some Candida albicans clinical strains. Baidam cultivar possessed higher antifungal activity (MIC=500-4000 µg/ml) as it contained higher contents of ellagic acid and gallic acid than Edor (MIC=1000-8000 µg/ml). For antibacterial activity, only corilagin and gallic acid possessed weak to moderate inhibitory effects against Staphylococcus aureus and Streptococcus mutans, respectively. Longan seed was then applied in the oral care products. Longan effervescent granule (5% extract) significantly reduced adhesion of C. albicans to acrylic strips. Mouthwash containing 0.5% extract exhibited good antifungal activity compared to a commercial product. These findings indicated that longan seed extract and its polyphenolic compounds can be used as an antifungal agent in oral care products for the treatment of opportunistic yeast infection.

Overexpression of cdk4 and p16 in oral lichen planus supports the concept of premalignancy.

BACKGROUND: Cell cycle arrest and increased cell proliferation have been demonstrated in oral lichen planus (OLP). This study evaluated the expression of cdk4, cdk6 and p16, important proteins in the G1 phase, in OLP and compared the expression of these proteins of OLP with those of normal mucosa. METHODS: Expression of cdk4, cdk6 and p16 were investigated in 23 OLP and 10 normal mucosae using immunohistochemistry technique. Positive cells were counted and presented as a percentage of positive cells. RESULTS: Expression of cdk4, cdk6 and p16 was observed in 3/10 (30%), 1/10 (10%) and none of normal mucosa, respectively. Expression of cdk4, cdk6 and p16 was detected in 18/23 (78.3%), 8/23 (34.8%) and 15/23 (65.2%), of OLP, respectively. The numbers of cdk4 and p16 positive cases of OLP were significantly higher than normal mucosa. In normal mucosa, the averages of the percentage of positive cells for cdk4 and cdk6 staining were 1.48 and 0.18, respectively. In OLP, the averages of the percentage of positive cells for cdk4, cdk6 and p16 staining were 2.73, 1.06 and 2.24, respectively. The percentage of cdk4-positive cells of OLP was significantly higher than those of normal mucosa group. CONCLUSION: Oral lichen planus demonstrated overexpression of cdk4 and p16, but not cdk6, suggesting that epithelial cells in OLP are in the hyperproliferative state and in cell arrest. Altered expression of cdk4 and p16 provides evidence of the malignant potential in OLP.

Alteration in the expression of cdk4 and cdk6 proteins in oral cancer and premalignant lesions.

BACKGROUND: Cdk4 and cdk6, key players in G1 phase, have been shown to play an important role in the development of oral squamous cell carcinoma (OSCC). This study investigated the expression of these two proteins in OSCC and premalignant lesions including oral leukoplakia (OL) with and without dysplasia and determined if alterations in the expression of these two proteins could be used as markers of malignant transformation. METHODS: Expressions of cdk4 and cdk6 were evaluated in 61 samples including OSCC, OL with and without dysplasia and normal oral mucosa using immunohistochemistry method. Nuclear staining of the keratinocytes was considered positive and the percentage of positive cells was calculated. RESULTS: Expression of cdk4 was found in 11/15 (73.33%) OSCC, 13/14 (92.85%) OL with dysplasia, 13/20 (65%) OL without dysplasia and 3/12 (25%) normal mucosa. Expression of cdk6 was detected in 9/15 (60%) OSCC, 3/14 (21.43%) OL with dysplasia, 5/20 (25%) OL without dysplasia and 1/12 (8.33%) normal mucosa. In cdk4 stained specimens, the frequency of positive cases and the percentage of positive cells in normal mucosa was significantly lower than OL with dysplasia and OSCC. For cdk6 staining, the prevalence of positive cases and the percentage of positive cells in normal mucosa were significantly lower than OSCC. CONCLUSIONS: Overexpressions of cdk4 and cdk6 were observed in OSCC, indicating that these two proteins play a crucial role in OSCC. The aberrant expression of cdk4 was found in OL with dysplasia, suggesting that cdk4 may be involved in the early event of carcinogenesis.

Expression of p16 in oral cancer and premalignant lesions.

BACKGROUND: Expression of p16 has been proposed as a marker for malignant transformation. This study aimed to evaluate p16 expression in oral squamous cell carcinoma (OSCC) and premalignant lesions including oral leukoplakia (OL) with and without dysplasia. METHODS: Expression of p16 was investigated in 56 samples including OSCC, OL with and without dysplasia, and normal oral mucosa. Expression of p16 was identified by immunohistochemistry, using the CINtecTM p16INK4a Histology Kit. Both nuclear and/or cytoplasmic staining of the keratinocytes were considered to be positive and the percentage of positive cells was calculated. RESULTS: Expression of p16 was detected in 3/16 (18.75%) cases of OSCC, in 4/15 (26.7%) cases of OL without dysplasia, and in none of OL with dysplasia and normal mucosa. No significant differences in p16 expression prevalence were found among OSCC, OL with and without dysplasia and normal mucosa. The percentages of positive cells in OSCC and OL without dysplasia were 0.89 and 0.17, respectively. No significant difference in the percentage of positive keratinocytes was found. CONCLUSION: As a marker, p16 is not reliable for oral mucosal dysplasia and malignant transformation.

Reduction of micronuclei in oral lichen planus supplemented with beta-carotene.

An elevated frequency of micronucleated exfoliated cells (MEC) in atrophic and erosive oral lichen planus (OLP) has been reported. To evaluate the effects of supplemental beta-carotene (BC) on MEC frequency in OLP lesions, we performed an open trial in 20 patients with atrophic and/or erosive OLP. Each patient received 15 mg of BC four times daily for 3 months. The frequency of MEC in both lesions and adjacent normal mucosa in each patient was evaluated and compared before and after supplementation. Serum levels of BC and retinol were also determined. After BC supplementation, all patients had higher levels of serum BC and retinol. The MEC frequency in OLP lesions was significantly reduced (P < 0.01). No significant changes were seen in the MEC frequency in adjacent normal mucosa. BC supplementation thus significantly reduces MEC frequency in atrophic and erosive OLP.

Detection of human papillomavirus in oral squamous cell carcinoma, leukoplakia and lichen planus in Thai patients.

Although tobacco, alcohol abuse and betel nut chewing habit are well recognized risk factors for oral squamous cell carcinoma (OSCC), there is evidence to indicate that human papillomavirus (HPV) may also play some inducing role. The purpose of this study was to investigate the presence of HPV in Thai patients with oral squamous cell carcinoma, leukoplakia and lichen planus using the polymerase chain reaction (PCR). Biopsies of oral squamous cell carcinoma, leukoplakia and lichen planus were obtained from 65 patients, 15 males and 50 females, aged between 30- 88 years old. Extracted DNA was evaluated for HPV infections by PCR analysis using consensus primers specific for L1 region of HPV. Only one sample (1.54%) was positive, suggesting that HPV may not play an important role in this group of Thai patients.

Frequency of micronucleated exfoliated cells in oral lichen planus.

OBJECTIVE: The purpose of this study was to determine the frequency of micronucleated exfoliated cells (MEC) in atrophic and erosive oral lichen planus (OLP). MATERIALS AND METHODS: Twenty-two patients with atrophic and/or erosive OLP participated in this study. Lesions were scored ranging from 0 (no lesion) to 5 (large erosion) according to the severity and assessed for MEC. Exfoliated cells were obtained by swabbing the lesions and normal-appearing mucosa adjacent to the lesions. Swabbing was also performed in age-sex-matched normal individuals. Five hundred exfoliated cells were screened for nuclear anomalies including micronuclei, karyorhexis, pycnosis, and chromatid clumping. RESULTS: The severity score of OLP ranged from 2 to 4 with the average of 2. The frequency of MEC in OLP patients was 3.79% and 0.37% in the lesions and normal-appearing mucosa, respectively. In normal individuals, the frequency of MEC was also 0.37%. Using a paired t-test, it was found that the MEC frequency in the OLP lesions was significantly elevated (p<0.01) as compared to that in normal-appearing mucosa adjacent to lesions and that in normal individuals. There were no statistically significant differences in the MEC frequency of the three severity scores as analyzed by Kruskal-Wallis one way analysis of variance on ranks (p>0.05). CONCLUSION: This study revealed an increase in micronuclei in OLP lesions. The results indicate genotoxic damage in atrophic and erosive OLP.

Interaction of the CDK2-associated protein-1, p12(DOC-1/CDK2AP1), with its homolog, p14(DOC-1R).

Human DOC-1/CDK2AP1 gene encodes a growth suppressor protein of 12kDa (p12(DOC-1/CDK2AP1)). Recently, p12(DOC-1/CDK2AP1) has been shown to associate with cell cycle proteins including CDK2 and DNA polymerase alpha/primase. It negatively regulates CDK2 activities and suppresses DNA replication. Therefore, identification of other p12(DOC-1/CDK2AP1) interacting proteins might clarify its role in the cell cycle regulation and carcinogenesis. The purpose of this study was to identify additional p12(DOC-1/CDK2AP1) interacting proteins using the yeast two-hybrid system. Using human p12(DOC-1/CDK2AP1) as a bait in a liver cDNA library screening, cDNA clones identical to human DOC-1R transcript were identified. The interaction between p12(DOC-1/CDK2AP1) and p14(DOC-1R) was verified in vitro and in cells. GST pull-down assay and immunoprecipitation experiments confirmed the interaction between the two proteins. The critical region for p12(DOC-1/CDK2AP1)'s interaction with p14(DOC-1R) was defined to amino acids 20-25 by using a series of deletion mutants as baits in the yeast two-hybrid system. Our data indicated that p12(DOC-1/CDK2AP1) could associate with its homologous protein, p14(DOC-1R).