Association between low bone mineral density and periodontitis in generally healthy perimenopausal women.

BACKGROUND: The association between low bone mineral density (BMD) and periodontitis in perimenopausal women is controversial. The purpose of this study was to determine whether osteoporosis or osteopenia is associated with periodontal disease in a population of adult women. METHODS: A sample of over-45-year-old women with or without low BMD underwent lumbar spine and hip bone densitometry and a complete periodontal examination. The extent/severity or absence of periodontal disease was noted using two different case definitions. Data were gathered on socio-economic status, medication history, systemic co-morbidities, alcohol or tobacco use as well as serum levels of calcium and vitamin D. RESULTS: One hundred seventy three women aged between 45 and 72 years old were recruited with a mean age of 57.8 years. One hundred and three had decreased BMD (61 with osteoporosis and 42 with osteopenia) and 70 were healthy. Moderate or severe periodontitis was present in 52.6% of the women. Multivariate analysis showed a clear association between low BMD and periodontitis, but only in women above 58 years old and independent of tobacco consumption or oral hygiene. CONCLUSION: In this sample of generally healthy perimenopausal women, low BMD was associated with clinical attachment level (CAL). Women over 58 years old with decreased BMD presented with a higher mean percentage of sites with CAL ≥ 4 mm as well as CAL ≥ 6 mm when compared to controls, independent of active smoking status or poor oral hygiene.

An update of knowledge on PD-L1 in head and neck cancers: Physiologic, prognostic and therapeutic perspectives.

Programmed cell death-ligand 1 (PD-L1) is a transmembrane protein that acts as a co-inhibitory factor in the immune response. Its receptor, programmed cell death protein 1 (PD-1), is found on immune cells, where binding to PD-L1 can reduce the proliferation of PD-1-positive cells, inhibit their cytokine secretion and induce apoptosis. PD-L1 in immune-privileged tissue plays a crucial role in peripheral tolerance. PD-L1 can be overexpressed in various malignancies, including oral squamous cell carcinoma, where it can attenuate the host immune response to tumour cells and has been associated with a worse prognosis. Monoclonal antibody therapies targeting the PD-1:PD-L1 axis have shown initial promise, but further research is needed to identify which patients will benefit. We provide an update of knowledge on PD-L1, including its structure, function and regulation. We also review studies on the overexpression of PD-L1 in cancer, specifically oral squamous cell carcinoma, and explore its potential value as a therapeutic target.

Malignant transformation risk of oral lichen planus: A systematic review and comprehensive meta-analysis.

OBJECTIVES: To evaluate current evidence on the malignant transformation of oral lichen planus (OLP), oral lichenoid lesions (OLLs), and oral lichenoid reactions (LRs) and to determine the variables with greatest influence on cancer development. MATERIAL AND METHODS: We searched PubMed, Embase, Web of Science, and Scopus for studies published before November 2018. We evaluated the quality of studies (QUIPS tool). We carried out meta-analyses to fulfill our objectives. We examined the between-study heterogeneity and small-study effects, and conducted sensitivity studies and subgroup analyses. RESULTS: Inclusion criteria were met by 82 studies (26,742 patients. The combined malignant transformation rate was 1.14% for OLP (95% CI = 0.84-1.49), 1.88% for OLLs (95% CI = 0.15-4.95) and 1.71% for LRs (95% CI = 0.00-5.46). Subgroup analysis revealed a higher malignant transformation rate in studies when the presence of epithelial dysplasia was not an exclusion criterion (p = 0.001), when both clinical and histopathological criteria were used for diagnosis (p < 0.001), when the follow-up was at least 12 months (p = 0.048), and when there was lower risk of potential bias (p = 0.002). Malignant transformation risk factors were: tongue localization (RR = 1.82, 95% CI = 1.21-2.74, p = 0.004), presence of atrophic-erosive lesions (RR = 4.09, 95% CI = 2.40-6.98, p < 0.001), tobacco use (RR = 1.98, 95% CI = 1.28-3.05, p = 0.002), alcohol consumption (RR = 2.28, 95% CI = 1.14-4.56, p = 0.02), and hepatitis C virus infection (RR = 4.46, 95% CI = 0.98-20.22, p = 0.053). CONCLUSIONS: The malignant transformation rates of OLP, OLLs and LRs are underestimated due essentially to restrictive diagnostic criteria, inadequate follow-up periods, and/or low quality of studies.

Predictive value of CCND1/cyclin D1 alterations in the malignant transformation of potentially malignant head and neck disorders: Systematic review and meta-analysis.

BACKGROUND: To evaluate published evidence on the predictive value of CCND1 amplification/cyclin D1 overexpression as malignant transformation risk markers in potentially malignant disorders (PMDs) of the head and neck. MATERIAL AND METHODS: We searched PubMed, Embase, Web of Science, and Scopus for studies published before June 2018. We conducted a meta-analysis to quantify the impact of CCND1/cyclin D1 amplification/overexpression on malignant transformation of head and neck PMDs. RESULTS: Nine studies met inclusion criteria. Quantitative evaluation indicated strong statistically significant association between CCND1/cyclin D1 amplification/overexpression and the progression of head and neck PMD to head and neck squamous cell carcinoma (risk ratio [RR] = 2.04, 95% confidence interval [CI] = 1.37-3.03, P < .001, and RR = 2.27, 95% CI = 1.32-3.91, P = .003, respectively). We observed moderate heterogeneity among studies (I2 = 40.7%), and we cannot rule out small-study effects such as publication bias. The oral cavity subgroup showed the strongest association between CCND1/cyclin D1 amplification/overexpression and progression to cancer. CONCLUSION: CCND1/cyclin D1 amplification/overexpression is important to predict the malignant transformation risk of head and neck PMDs, especially oral PMDs.

Clinicopathological significance of tumor cyclin D1 expression in oral cancer.

OBJECTIVE: To evaluate the association of cyclin D1 overexpression with clinicopathological parameters classically considered of prognostic value in OSCC (T, N, M, clinical stage, degree of differentiation, invasive morphology and, cellular proliferation index). DESIGN: A retrospective immunohistochemical study was conducted of cyclin D1 and ki-67 expression in 68 OSCCs from 54 patients. Cases were scanned using a digital pathology system. The tumor expression of markers was assessed in four randomly selected fields (40x), and a semi-automatized count was conducted of cyclin D1-positive and -negative cells. RESULTS: Cyclin D1 overexpression was found in 28.7% of the cases of OSCC. It was significantly and positively associated with the following clinicopathological parameters: low tumor differentiation degree (p = 0.030), invasive morphology (p = 0.045), and proliferative phenotype according to tumor cell ki-67 expression (p = 0.018). CONCLUSIONS: Cyclin D1 overexpression is an event of oral carcinogenesis associated with clinicopathological parameters classically associated with a poor prognosis in patients with OSCC.

Quality of life during pregnancy and its influence on oral health: a systematic review / Calidad de vida durante el embarazo y su influencia en la salud bucal: una revisión sistemática

Abstract: Objective: To perform a systematic review of scientific literature on the impact of oral health on the quality of life of pregnant women. Methods: A systematic search following PRISMA guidelines was carried out and 16 specific articles/studies on the subject were selected. Results: Pregnant women's quality of life (QoL) is related to age, number of pregnancies, pain, difficulty eating and presence of dental caries. Quality of life was directly related to oral health. Conclusions: It was found that most studies associating QoL and oral health during pregnancy were cross-sectional and observational; therefore, for a better understanding of these impacts, performing longitudinal studies from the beginning of pregnancy until postpartum is necessary. The need for preventive oral health counseling and dental care assistance during pregnancy is highlighted.

Objetivo: Realizar una revisión sistemática de la literatura científica sobre el impacto de la salud oral en la calidad de vida de las embarazadas. Métodos: Se lleva a cabo una búsqueda sistemática y se seleccionaron 16 artículos específicos sobre el tema, siguiendo las directrices PRISMA. Resultados: La calidad de vida (CdV) en la embarazada está relacionado con la edad, número de embarazos, dolor, dificultad para comer y presencia de caries. La calidad de vida se relacionó directamente con la salud oral. Conclusiones: A través de esta revisión se encontró que la mayoría de los estudios que relacionaban la CdV y la salud oral durante la gestación fueron de corte observacional transversal, por ello para una mejor comprensión de estos impactos, es necesario realizar estudios longitudinales desde el comienzo del embarazo hasta el posparto. Se destaca la necesidad de asesoramiento de salud oral preventiva y una ruta de atención dental durante el embarazo.

Prognostic and clinicopathological significance of CTTN/cortactin alterations in head and neck squamous cell carcinoma: Systematic review and meta-analysis.

BACKGROUND: To evaluate the prognostic significance of CTTN/cortactin alterations in head and neck squamous cell carcinoma (HNSCC). MATERIAL AND METHODS: We searched PubMed, Embase, Web of Science, and Scopus for studies published before May 2018. We conducted a meta-analysis to quantify the impact of CTTN/cortactin alterations on clinicopathological and survival variables. RESULTS: Eighteen studies (1633 patients) met inclusion criteria. Quantitative evaluation revealed a strong association of CTTN/cortactin alterations with N+ status (P < .001), higher T status (P < .001), advanced clinical stage (P < .001), high histological grade (P = .001), and lower overall survival (OS) (P < .001). We found heterogeneity in T status, histological grade, and OS and observed small-study effects on N status and OS. In subgroup analyses, a significant association of CTTN amplification and cortactin overexpression with the above variables was preserved. The strongest association between CTTN/cortactin alterations and a worse outcome was observed in the subgroups of Asian patients and pharyngolaryngeal squamous cell carcinomas. CONCLUSIONS: CTTN/cortactin alterations should be evaluated to predict the HNSCC prognosis.

Asymmetrical proliferative pattern loss linked to cyclin D1 overexpression in adjacent non-tumour epithelium in oral squamous cell carcinoma.

OBJECTIVE: To evaluate cyclin D1 overexpression in oral squamous cell carcinomas and adjacent non-tumour epithelium as a biomarker of premalignant fields and a risk factor for multiple tumour development. DESIGN: We studied cyclin D1 expression in 54 patients with 68 oral squamous cell carcinomas plus adjacent non-tumour epithelia characterized as close (n = 58) or distant (n = 41) from the invasion point. Randomized 40x fields were evaluated (4 in tumour tissue and 1 each in close and distant non-tumour epithelium). Expression in non-tumour epithelium was evaluated in basal, parabasal, middle-third and upper-third compartments. RESULTS: Cyclin D1 overexpression was found in both carcinomas and non-tumour epithelia. Nuclear expression in basal and parabasal layers of distant epithelium was significantly increased in patients with multiple tumours (p < 0.001). A significant association between cyclin D1 overexpression in different epithelial layers was found in both close and distant epithelia. A significant association was found between nuclear expressions of cyclin D1 and Ki-67 in the basal layer of distant epithelium (p = 0.02). CONCLUSIONS: Cyclin D1 overexpression is an early event in oral carcinogenesis linked to loss of the physiological asymmetrical proliferation pattern. Cyclin D1 overexpression in basal and parabasal layers of epithelia distant from the invasion point may act as a potential marker of premalignant fields and multiple tumour development.

An update of knowledge on cortactin as a metastatic driver and potential therapeutic target in oral squamous cell carcinoma.

Cortactin is a protein encoded by the CTTN gene, localized on chromosome band 11q13. As a result of the amplification of this band, an important event in oral carcinogenesis, CTTN is also usually amplified, promoting the frequent overexpression of cortactin. Cortactin enhances cell migration in oral cancer, playing a key role in the regulation of filamentous actin and of protrusive structures (invadopodia and lamellipodia) on the cell membrane that are necessary for the acquisition of a migratory phenotype. We also analyze a series of emerging functions that cortactin may exert in oral cancer (cell proliferation, angiogenesis, regulation of exosomes, and interactions with the tumor microenvironment). We review its molecular structure, its most important interactions (with Src, Arp2/3 complex, and SH3-binding partners), the regulation of its functions, and its specific oncogenic role in oral cancer. We explore the mechanisms of its overexpression in cancer, mainly related to genetic amplification. We analyze the prognostic implications of the oncogenic activation of cortactin in potentially malignant disorders and in head and neck cancer, where it appears to be relevant in the development of lymph node metastasis. Finally, we discuss its usefulness as a therapeutic target and suggest future research lines.

Prognostic and clinicopathological significance of cyclin D1 expression in oral squamous cell carcinoma: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the prognostic significance of cyclin D1 (CD1) overexpression in OSCC. MATERIAL AND METHODS: We searched studies published before August 2017 (Pubmed, Embase, Web of Science, Scopus). We evaluated the quality of the studies included (Quality in Prognosis Studies [QUIPS] tool). The impact of CD1 overexpression on overall survival and disease-free survival, T status, N status, stage, and histological degree was meta-analyzed. We analyzed heterogeneity among studies, conducted sensitivity analyses, analyzed small-study effects, and conducted subgroup analyses. RESULTS: 31 studies (2942 patients) met inclusion criteria. Qualitative evaluation demonstrated that not all studies were performed with the same rigor, finding the greatest risk of bias in the study confounding domain. Quantitative evaluation showed that CD1 overexpression had a strong statistical association with worse overall survival (HR = 2.00, 95% CI = 1.59-2.51, p < 0.001), worse disease-free survival (HR = 1.46, 95% CI = 1.13-1.87, p = 0.003), higher T status (OR = 1.51, 95% CI = 1.07-2.13, p = 0.02), N+ status (OR = 2.16, 95% CI = 1.60-2.92, p < 0.001), advanced stage (OR = 1.44, 95% CI = 1.15-1.81, p = 0.002), and high histological grade (OR = 1.60, 95% CI = 1.12-2.29, p = 0.010). We observed heterogeneity in all parameters except for disease-free survival and clinical stage. We found effect of small studies on T and N status. The tonguel SCC subgroup showed the strongest association between CD1 overexpression and worse development. In addition, application of a cutoff point ≥10% tumor cells with nuclear CD1 expression maintained most of the significant associations reported. CONCLUSIONS: These findings indicate that immunohistochemical assessment of CD1 overexpression may be useful as a prognostic biomarker for OSCC.

Relevance of chromosomal band 11q13 in oral carcinogenesis: An update of current knowledge.

An important event in oral carcinogenesis is the amplification of chromosomal band 11q13, in which numerous oncogenes and some tumor-suppressor genes are localized and frequently co-amplified during the malignant transformation of oral epithelium. The objectives of this study were to review published data on the involvement of 11q13 amplification in oral cancer, to provide an update on novel concepts and terminology related to gene amplification, and to explore the composition of the 11q13 amplicon in OSCC, including its most relevant amplicon cores and potential drivers. We report on the critical oncogenes and tumor-suppressor genes in 11q13 that may play a major role in oral cancer, focusing on their functions, on the characteristics acquired by their amplification, and on their clinicopathological implications. Finally, we discuss the possible usefulness of the 11q13 region as a therapeutic target in oral cancer.

Oral Hygiene in the Elderly with Different Degrees of Cognitive Impairment and Dementia.

The control of bacterial dental plaque through daily oral hygiene is essential to prevent oral diseases such as caries or periodontal disease, especially in at-risk populations, including the elderly with mild cognitive impairment and dementia. The aim of this study was to determine the association between different levels of cognitive impairment and dementia in an elderly population and their capacity to maintain adequate oral hygiene. A case-control study (elderly with versus without mild cognitive impairment or dementia) was performed in Granada, Spain. Outcome variables were tooth/prosthesis-brushing frequency/day, bacterial plaque index, and gingival bleeding index. Statistical models were adjusted by age, sex, educational level, and tobacco and alcohol habits. The study included 240 cases and 324 controls. The final model, adjusted by age, sex, educational level, and tobacco and alcohol consumption, showed a significant association between degree of cognitive impairment and daily oral hygiene, accumulation of bacterial plaque, and gingival bleeding. In summary, deficient daily oral hygiene, evidenced by greater bacterial dental plaque accumulation and gingival inflammation, is independently associated with cognitive impairment, even at its earliest stage.

Association between general and oral health-related quality of life in patients treated for oral cancer.

BACKGROUND: Less is known about the association between general health-related quality of life (HRQoL) and oral HRQoL (OHRQoL) among patients with specific diseases. The aim of this study was to assess the association between patient-centered outcome measurements (HRQoL and OHRQoL) of oral cancer patients at least 6 months after treatment. MATERIAL AND METHODS: HRQoL was measured with the 12-Item Short Form Health Survey (SF-12); OHRQoL was evaluated using the Oral Health Impact Profile (OHIP-14) and the Oral Impacts on Daily Performances (OIDP). RESULTS: Higher OHRQoL scores were associated with lower SF-12 domains scores. The OHIP-14 explained 16.5 % of the total variance of SF-12 Physical Component Summary (PCS) and the OIDP explained 16.1 %. In the SF-12 Mental Component Summary (MCS), the total variance explained was 23.9 % by the OHIP-14 and 21.8 % by the OIDP. CONCLUSIONS: There was a significant association between long-term OHRQoL and HRQoL in oral and oropharyngeal cancer patients. These results may help to carry out new interventions aiming to improve patient's life overall.

Oral health in the elderly patient and its impact on general well-being: a nonsystematic review.

Data on the oral health of the elderly depict a worrying situation, with an elevated prevalence of caries and moderate periodontal disease, frequent edentulism, and numerous cases of dry mouth and oral cancer. There is wide evidence that periodontitis is a risk factor for certain systemic diseases, and impaired oral health has been associated with mastication and nutritional problems, especially among the elderly, with highly negative effects on their quality of life. In this nonsystematic review, the authors discuss the importance of evaluating the oral health of the geriatric population in a comprehensive manner, beyond simple clinical assessments.

Oral and general health-related quality of life in patients treated for oral cancer compared to control group.

BACKGROUND: Health-related quality of life (HRQoL) is gaining importance as a valuable outcome measure in oral cancer area. The aim of this study was to assess the general and oral HRQoL of oral and oropharyngeal cancer patients 6 or more months after treatment and compare them with a population free from this disease. METHODS: A cross-sectional study was carried out with patients treated for oral cancer at least 6 months post-treatment and a gender and age group matched control group. HRQoL was measured with the 12-Item Short Form Health Survey (SF-12); oral HRQoL (OHRQoL) was evaluated using the Oral Health Impact Profile (OHIP-14) and the Oral Impacts on Daily Performances (OIDP). Multivariable regression models assessed the association between the outcomes (SF-12, OHIP-14 and OIDP) and the exposure (patients versus controls), adjusting for sex, age, social class, functional tooth units and presence of illness. RESULTS: For patients (n = 142) and controls (n = 142), 64.1% were males. The mean age was 65.2 (standard deviation (sd): 12.9) years in patients and 67.5 (sd: 13.7) years in controls. Patients had worse SF-12 Physical Component Summary scores than controls even in fully the adjusted model [ß-coefficient = -0.11 (95% CI: -5.12-(-0.16)]. The differences in SF-12 Mental Component Summary were not statistically significant. Regarding OHRQoL patients had 11.63 (95% CI: 6.77-20.01) higher odds for the OHIP-14 and 21.26 (95% CI: 11.54-39.13) higher odds for OIDP of being in a worse category of OHRQoL compared to controls in the fully adjusted model. CONCLUSION: At least 6 months after treatment, oral cancer patients had worse OHRQoL, worse physical HRQoL and similar psychological HRQoL than the general population.

Evaluation of p53, caspase-3, Bcl-2, and Ki-67 markers in oral squamous cell carcinoma and premalignant epithelium in a sample from Alava Province (Spain).

OBJECTIVE: The objective of this study was to determine whether alterations in the expression of p53, caspase-3 Bcl-2, and ki-67 appear early in premalignant oral epithelium and show clonal behavior. STUDY DESIGN: Samples from 41 tumors with their adjacent non-tumor epithelia were immunohistochemically analyzed using monoclonal antibodies that recognize p53, caspase-3, Bcl-2, and Ki-67 RESULTS: A statistically significant association was found between the expression in tumor and adjacent epithelium of p53, caspase-3, and Bcl-2 but not of k-67. A significant association was observed between the expression of ki-67 and p53 in both localizations. In non-tumor (premalignant) epithelium samples, there was a significant inverse relationship between the expressions of p53 and caspase-3 and a significant direct relationship between the expressions of p53 and Bcl-2. CONCLUSIONS: Alterations in these proteins appear to operate in combination with premalignant epithelia to create hyperproliferative cell states that favor the acquisition of summative oncogenic errors that confer invasive capacity.

A role for the substance P/NK-1 receptor complex in cell proliferation in oral squamous cell carcinoma.

OBJECTIVE: To investigate the presence and distribution of substance P (SP) and neurokinin 1 receptor (NK-1R) in oral squamous cell carcinoma (OSCC) and their relationship with proliferation. PATIENTS AND METHODS: Ninety OSCCs from 73 patients were immunohistochemically analyzed using monoclonal antibodies against SP, NK-1R and Ki-67 in a case and control study. RESULTS: Seventy-one percent (n=49) of cases expressed SP on tumour cell membrane, 81.3% (n=69) in cytoplasm, 39.4% (n=28) in nucleus, 81.6% (n=71) in infiltrating lymphocytes, and 58.1% (n=43) in peritumoural or intratumoural blood vessels; 14% (n=12) of cases expressed NK-1R on tumour cell membrane, 50% (n=43) in cytoplasm, 48.3% (n=42) in infiltrating lymphocytes and 22.5% (n=18) in tumour blood vessels. All cases expressed Ki-67, which was expressed in >25% of tumour cells in 79.8% of cases (n=63). Direct significant associations were observed in SP expression between different tissue levels (p<0.01), between SP and NK-1R tumour cell membrane expression (p<0.01), and between joint SP and NK-1R expression in tumour cell cytoplasm and a higher expression of Ki-67 (p<0.05). CONCLUSION: The ubiquitous presence of SP strongly suggests a role for SP/NK-1R complex in tumour development and progression and possibly for NK-1R antagonists, such as L-773060, in the management of patients with oral cancer.

World dental research production: an ISI database approach (1999-2003).

The objective of this study was to obtain a geographic world map of scientific production in dentistry by analysing published papers. Articles and reviews in the Dentistry, Oral Surgery & Medicine category published from 1999 to 2003 were accessed through the ISI database. The data were analyzed quantitatively (number of documents, number of researchers, productivity, interannual variation rate and relative specialization index), qualitatively (weighted impact factor, relative impact factor, citation rate per document and top 5 publications) and socioeconomically (number of documents per inhabitant and per dentist and in relation to the country's GDP). The USA, UK, Japan and Scandinavian countries were found to be the most productive countries (number of publications). Publications from Scandinavian countries were also of high quality as measured by Impact Factor and Citation Rate, while the UK had one of the highest productivity rates (number of documents per researcher).

Adhesion molecule CD44 expression in non-tumor epithelium adjacent to laryngeal cancer.

BACKGROUND: Studies of adjacent non-tumor epithelia (ANTE) of laryngeal cancer have presented contradictory results regarding the expression of the adhesion molecule CD44 and its role as an early event and risk marker for progression to cancer. METHODS: An immunohistochemical study was performed on changes in CD44 expression in the ANTE and tumor tissue of 112 cases of laryngeal cancer, using the anti-CD44 monoclonal antibody DF1485. The aim was to evaluate the importance of these changes as an early event in laryngeal carcinogenesis. RESULTS: The ANTE were histologically hyperplastic in 107 cases (95.5%) and presented epithelial dysplasia in 105 cases (93.7%). A significant association between tumor and epithelial CD44 expression was observed in both hyperplastic (p < 0.001) and dysplastic (p < 0.001) ANTE. There was no significant association between ANTE CD44 expression and clinical or histopathological relevant data. CONCLUSIONS: Loss of CD44 expression in ANTE can be considered an early event in laryngeal carcinogenesis and a marker of major alterations in CD44 expression in the derived tumor tissue.

Analysis of p53 protein by PAb240, Ki-67 expression and human papillomavirus DNA detection in different types of odontogenic keratocyst.

OBJECTIVE: To investigate the possible association between alterations in the p53 system and human papillomavirus (HPV) infection in the etiology of odontogenic keratocysts (OKCs) and to study proliferation and epithelial maturation patterns by topographic analysis of Ki-67 expression. MATERIALS AND METHODS: Eighty-three OKC samples (29 cases associated with nevoid basal cell carcinoma syndrome, 29 solitary non-recurrent cases 20 solitary recurrent cases, and 5 chondroid keratocysts) were studied by immunohistochemistry to detect p53 protein (PAb 244) and Ki-67 (MIB-1) expression, and by PCR to detect HPV DNA. RESULTS: Twelve cases (14.6%) expressed p53 protein; no case showed the presence of HPV DNA; 9 cases (11%) presented with mild epithelial dysplasia. The suprabasal expression of Ki-67 was significantly more frequent than its basal expression (p < 0.001). p53 protein expression was significantly associated with the presence of epithelial dysplasia (p = 0.023). Ki-67 expression was not associated with OKC type, the presence of dysplasia, or p53 expression. CONCLUSION: HPVs do not participate in the etiology of OKC, and it appears unlikely that a p53 gene mutation mechanism plays a major role in the genesis of OKC. OKCs show proliferation and genuine maturation behavior reminiscent of benign neoplasms with local destructive capacity.