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PubMed2006

p16(INK4a) promoter hypermethylation in oral scrapings of oral squamous cell carcinoma risk patients.

Aberrant promoter hypermethylation is common in oral squamous cell carcinoma (OSCC) and may be useful as a marker for cancer cells. The aim of our study was to assess whether the detection of hypermethylation of the promoter region of p16(INK4a) in oral cytological samples could be a marker in patients with risk of developing an OSCC. Hypermethylation was detected in 20% (29/145) of the cases analyzed. These findings provide further evidence that the inactivation of p16(INK4a), due to methylation, is an early event in the carcinogenic pathway of OSCC.

Aged↗
PubMed2005

Pigmented lesions of the oral cavity.

The management of pigmented oral lesions varies based on the diagnosis, ranging from the extremes of patient reassurance to radical surgical excision. This article delineates the factors that will help the clinician differentially diagnose pigmented lesions of the oral cavity. The parameters of care regarding the spectrum of pigmentations are also reviewed.

Diagnosis, Differential↗
PubMedDate not supplied

Chronic, reactive conditions of the oral cavity simulating mucosal carcinomas: CT and MR imaging findings with pathologic correlation in five patients.

To investigate the radiologic and pathologic findings of chronic, inflammatory, reactive conditions of the oral cavity, which clinically and radiologically simulate mucosal malignancy, computed tomography (CT; n=4) and magnetic resonance (MR; n=2) images, as well as surgical specimens, obtained from five patients with surgically proved, chronic inflammatory mass of the oral cavity were retrospectively reviewed. All patients had a palpable mass or ulcerative lesion in the oral cavity. On CT and MR images, all three lesions in the oral tongue and one lesion in the retromolar trigone were seen as a superficial, ill-marginated, well-enhancing ellipsoid or focal soft tissue mass. Pathologic examinations revealed various depths and degrees of acute and chronic inflammation, granulation tissue, and fibrosis in the subepithelial stroma, accompanied by pseudoepitheliomatous hyperplasia in these four patients. In the remaining one patient with lesion in the hard palate, CT showed a relatively well-marginated, well-enhancing soft tissue mass, which histologically proved to be irritation fibroma. Neither clinical nor radiologic manifestations could afford clues to make the correct diagnosis, which therefore should rely on histology. Some forms of chronic, inflammatory, reactive conditions of the oral cavity are nearly indistinguishable from the malignant tumors both clinically and radiologically. Knowledge of this entity may obviate the unnecessary and somewhat disfiguring operation.

Adult↗
PubMed2004

Lethal synergistic effect of cigarette smoke and saliva in an in vitro model: does saliva have a role in the development of oral cancer?

Exposure of oral mucosal cells to cigarette smoke induces oral cancer, presumably via the injurious effect of free radicals. To explore the effects of cigarette smoke on cells in the presence of saliva, we used peripheral blood lymphocytes (PBL) and exposed them to cigarette smoke, alone or in the presence of saliva. After 80 min exposure to cigarette smoke alone, a time-dependent cellular loss and survival rate of 52% was observed. By contrast, following the exposure of the lymphocytes to cigarette smoke in the presence of saliva, less than 20% of the cells survived. Saliva secreted from the submandibular/sublingual (Sm/Sl) glands was highly cytotoxic, while saliva secreted from the parotid glands was only moderately cytotoxic. Redox active iron ions in saliva and aldehydes in cigarette smoke were shown to play the major injurious roles in this synergistic phenomenon. The salivary-borne redox active iron ions participate in Fenton and Haber-Weiss reactions to transform low-reactive free radicals, which originate from cigarette smoke into highly-reactive .OH(-)-free radicals. In light of these results, a comprehensive mechanism for the induction of oral cancer by cigarette smoke is suggested where saliva may be a pivotal player.

Adult↗
PubMed2006

Mitochondrial DNA sequence alterations observed between blood and buccal cells within the same individuals having betel quid (BQ)-chewing habit.

There are hundreds of millions of betel quid (BQ) lovers widely spreading around the world. Compositions in BQ may generate reactive oxygen species, which would induce DNA damage. However, oral epithelial cells as well as blood have often been used as reference samples in comparison with the mitochondrial DNA (mtDNA) sequence of hairs. The main purpose of this study was to investigate the extent of mtDNA sequence variation in regular BQ-chewers' oral epithelial cells, and thus to evaluate the forensic availability of the buccal cells from BQ-chewers using the mtDNA markers. The hypervariable segments I and II in the D-loop control region of mtDNA between paired samples of blood and buccal scrape cells from 75 non-BQ-chewers (to be a control group), 60 BQ-chewers, and 67 oral cancerous patients were DNA sequenced and compared. Among the three groups, the alteration rates of 1.3% (1 out of 75), 10% (6 out of 60), and 61% (41 out of 67) were identified from the control, BQ-chewers, and the cancerous group, respectively. In the cancerous group, as expected, high rate of DNA alteration between blood and buccal samples was found. In the BQ-chewers, one and five individuals had the length and point alterations, respectively. Interestingly, most of point alteration sites, e.g., mtDNA positions 153, 16189, 16093 identified from BQ-chewers, were also observed in previous literatures. As for the control subjects, one case with point alteration, and none with length alteration, was identified. For all the three groups, not only the oral cells but also the normal blood samples exhibited high frequency (>55%) of length heteroplasmy at poly-(C)n track. Statistical analyses revealed that significance was observed between the severity of mtDNA alteration in BQ-chewers' oral epithelial cells and the history of BQ-chewing (p = 0.02), with a tendency of positive association. Based on the guidelines by Carracedo et al., we suggest that the interpretation of mtDNA variations between criminal evidences and the oral epithelial cells (as a reference or known sample) from BQ-chewers should be performed with particular caution using the PCR-based mtDNA sequencing. Our findings would be valuable in mtDNA analysis of hair evidence, especially for those countries where the habit of BQ-chewing is popular.

Adolescent↗
PubMed2005

Severity of oral mucositis correlates with the response of oral cancer to preoperative radiochemotherapy.

Oral mucositis is a dose-limiting toxic effect of radiotherapy and chemotherapy on oral cancer. The purpose of the present study is to assess the relationship between tumor response and oral mucositis in preoperative radiochemotherapy for oral cancer retrospectively. Fifty-four cases of oral squamous cell carcinoma were treated with concurrent radiochemotherapy prior to surgery. When oral mucositis was evaluated with the WHO scale, severe oral mucositis (Grades 3 and 4) developed in 22 cases (41%). A more than 50% reduction in tumor size was clinically observed in 38 cases (70%). From histopathological analysis of the surgical specimens all tumor cells observed appeared to be non-viable in 16 cases (29%). The cases with Grade 1, Grade 2, Grade 3 and Grade 4 oral mucositis included 33%, 62%, 85% and 89% of clinical good-response cases and 0%, 24%, 31% and 55% of histopathological good-response cases, respectively. This retrospective study suggests that severe oral mucositis promises a good response of oral squamous cell carcinoma to radiochemotherapy.

Aged↗
PubMed2006

Human papillomaviruses in oral squamous cell carcinoma and pre-cancerous lesions detected by PCR-based gene-chip array.

Human papillomavirus (HPV) infection is a significant risk factor for uterine cervical carcinoma. Many studies have also demonstrated the presence of HPV in oral epithelia tissue, but the role of HPV infection in oral squamous cell carcinoma (OSCC) is still controversial. The aim of this study was to determine the frequency and type of HPV in OSCC and oral pre-cancerous lesions. DNA samples were collected by cytobrushing from 51 patients with OSCC, 46 with oral pre-cancerous lesions and 90 normal controls. Nested polymerase chain reaction and gene-chip arrays were used to identify the HPV types in the samples. In pre-cancerous lesions, there was a higher frequency of HPV of any type (14/46, OR = 2.844, CI = 1.186-6.816, P = 0.0216) and of low-risk HPV types (9/46, OR = 5.529, CI = 1.597-19.14, P = 0.0096) than in control samples. The prevalence of high-risk types was significantly higher in OSCC than in control lesions (11/51 vs 8/90, OR = 2.819, CI = 1.051-7.558, P = 0.0420) but this was not the case for HPV of any type (13/51 vs 12/90, OR = 2.244, CI = 0.9266-5.337, P = 0.1066). High-risk HPV types are prevalent in OSCC and may play a role in its progression, while low-risk types are associated with oral pre-cancerous lesions.

Adult↗
PubMed2005

Oral tolerance and its relation to food hypersensitivities.

The gastrointestinal tract is the largest immunologic organ in the body. It is constantly bombarded by a myriad of dietary proteins. Despite the extent of protein exposure, very few patients have food allergies because of development of oral tolerance to these antigens. Once proteins contact the intestinal surface, they are sampled by different cells and, depending on their characteristics, result in different responses. Antigens might be taken up by Microfold cells overlying Peyer's patches, dendritic cells, or epithelial cells. Different cells of the immune system participate in oral tolerance induction, with regulatory T cells being the most important. Several factors can influence tolerance induction. Some are antigen related, and others are inherent to the host. Disturbances at different steps in the path to oral tolerance have been described in food hypersensitivity. In this review we provide an overview of oral tolerance and cite data related to food hypersensitivity wherever evidence is available.

Age Factors↗
PubMed2005

Superiorly based and island masseter muscle flaps for repairing oropharyngeal defects.

INTRODUCTION: Tumours of the posterior part of the mouth and/or the oropharynx are often diagnosed at advanced stages. Reconstruction in this region has advanced considerably during the last three decades. Although microsurgery has offered major progress and has obviously improved the patients' outcome, the use of local and regional flaps generally remains an ideal solution for reconstruction. MATERIAL AND METHODS: Between January 1994 and December 2001, the defects resulting from resection in 22 out of 38 patients with retromolar and/or anterior faucial pillar squamous cell carcinomas treated at this institution, were repaired by one of two types of masseter muscle flaps. The first type is the superiorly based or cross-over masseter muscle flap, and the second type the island muscle flap (being a modification of the first type). RESULTS: The superiorly based masseter muscle flap was used in 12 patients and the island masseter muscle flap in 10. Both techniques offer a quick and reliable method for repairing oropharyngeal defects in oncologically "safe" cases. Neither require elaborate technique or aftercare. CONCLUSION: The island masseter muscle flap has an advantage over the superiorly based masseteric flap, as it is more flexible, pliable for larger defects, and causes no postoperative trismus.

Adult↗
PubMed2004

The inverted temporalis muscle flap for intraoral reconstruction: its rationale and the results of its application.

PURPOSE: The purpose of this article was to show the discrepancies among the different parts of the temporalis muscle flap (TMF), to introduce a new rotational arc for the TMF based on these findings, and to examine the outcomes associated with the use of this modified method. MATERIALS AND METHODS: Two models were established on 5 human skulls to mimic the situations with the usual dissection technique or the extended dissection technique for the TMF. The lengths of the anterior part, the middle part, and the posterior part of the flap were measured and analyzed for statistical significance. A new rotational arc for the TMF was introduced, in which the flap was inverted beneath the zygomatic arch, placing the temporalis fascia away from the oral side. Seventeen consecutive oral cancer cases treated with either the traditional method or the inverted method of flap transposition were reviewed and divided into 2 groups dictated by the rotational arcs of their flaps. The traditional TMF was used in 11 cases and the inverted TMF was used in 6 cases. Clinical examination and imaging studies were used for assessment of outcome, and the results from the 2 patient groups were compared. RESULTS: The middle and posterior parts of the temporalis muscle were significantly longer than the anterior part on the skull models. However, the middle and posterior parts did not differ greatly in length. The extended dissection technique increased the flap length except for the anterior part. Both flaps were successful in closing the defects in all cases and healed well. No muscle necrosis was observed. However, the patients receiving the traditional TMF developed noticeable cheek fullness in 4 instances, sialocele in 3, significant reduction of range of mouth opening in 2, and distinct velopharyngeal insufficiency in 2, whereas only 1 case in which the inverted TMF was used developed cheek fullness. CONCLUSIONS: The middle or posterior part of the temporalis flap is preferred over the anterior part for covering distant defects because of its extra length. The inverted TMF is simple and safe to apply. It can extend farther in the posterior oral cavity and has fewer complications than the traditional TMF.

Adult↗
PubMed2006

Evaluation of nuclear morphometry and DNA ploidy status for detection of malignant and premalignant oral lesions: quantitative cytologic assessment and review of methods for cytomorphometric measurements.

PURPOSE: Detection of a precancerous or cancerous lesion when small is one of the most important factors to improve 5-year survival rates of oral cancer. Although surgical biopsy is the most definitive method for diagnosing oral lesions, it is impractical to routinely subject large numbers of patients to biopsy. Recently, cytomorphometric assessments improved by advanced computer-assisted image analysis systems have gained importance. This study was established to evaluate the efficacy of nuclear cytomorphometric analysis and DNA ploidy status for the detection of oral malignancies. Methods used for cytomorphometric analysis were also reviewed. PATIENTS AND METHODS: Oral mucosal smears (n = 44) were obtained from patients (n = 22) presenting with various oral lesions using a cytobrush immediately before biopsy. Cytomorphometric measurements and nuclear Feulgen DNA content analysis were carried out after the Feulgen staining procedure. Smears from the lesion site constituted the study group whereas contralateral healthy mucosal sites served as control. RESULTS: DNA ploidy analysis revealed 20 diploid (90.9%) and 2 aneuploid DNA patterns (9.1%) sampled from the lateral margin of the tongue and floor of the mouth. When only malignant lesions were considered, aneuploidy rate was 16.7% whereas a diploid pattern was indicated for 83.3% of the sample. With cytomorphometric measurements, a statistically significant difference was shown for nuclear perimeter, area, diameter equivalent to circle, minimum and maximum Feret, intensity, DNA content (c) and DNA index values. CONCLUSIONS: Cytomorphometric analysis via oral brush biopsy is a valuable adjunct to biopsy for identification of premalignant and early stage cancerous oral lesions as a rapid and minimally invasive procedure with high specificity and sensitivity rates, requiring no topical or local anesthetic.

Adult↗
PubMed2007

Lack of association between proliferative verrucous leukoplakia and human papillomavirus infection.

PURPOSE: To analyze proliferative verrucous leukoplakia (PVL) for the presence of human papillomavirus (HPV) in different stages of the disease. MATERIALS AND METHODS: We studied 13 patients with PVL. In 10 patients (76.9%), a lesional biopsy was taken and frozen at -40 degrees C. Four patients were instructed to mouth rinse with sterile sera. The biopsy and rinse samples were analyzed for HPV by PCR. RESULTS: We did not detect HPV infection in the PVL tissue or in the oral rinse of any of the 13 patients in any stage of the disease analyzed, neither in oral squamous cell carcinoma nor in the simple hyperkeratosis. CONCLUSION: There was no association between PVL and HPV infection in our patients.

Aged↗
PubMed2006

Mechanical allodynia and thermal hyperalgesia induced by experimental squamous cell carcinoma of the lower gingiva in rats.

UNLABELLED: We developed a rat model of oral cancer pain by inoculating cancer cells into the lower gingiva. A squamous cell carcinoma (SCC) derived from Fisher rats, SCC-158, was inoculated into the subperiosteal tissue on the lateral side of the lower gingiva in male Fisher rats. Inoculation of cancer cells induced marked mechanical allodynia and thermal hyperalgesia in the ipsilateral maxillary and mandibular nerve area. Infiltration of the tumor cells into the mandible and the completely encompassed inferior alveolar nerve was observed. Calcitonin gene-related peptide (CGRP)-, substance P (SP)-, ATP receptor (P2X(3))-, and capsaicin receptor (TRPV1)-immunoreactive cells strikingly increased in the small-cell group of trigeminal ganglia (TGs) after tumor cell inoculation. The TRPV1-immunoreactive cells also increased in the medium- and large-cell groups. Retrograde tracing combined with immunofluorescence techniques revealed the increased expression of peptides and the receptors in maxillary nerve afferent neurons. These results suggest that inoculation of SCC cells into the lower gingiva produces mechanical allodynia and thermal hyperalgesia, indicating the establishment of a novel rat model of oral cancer pain. Increased expression of CGRP, SP, P2X(3), and TRPV1 in the TG may be involved in the behavioral changes in this model. PERSPECTIVE: To clarify the mechanisms of oral cancer pain, we examined the expression of calcitonin gene-related peptide, substance P, ATP receptor P2X(3), and capsaicin receptor TRPV1 in trigeminal ganglia. Characterizations of these molecular systems which mediate pain perception are important to develop novel clinical tools for promoting relief of oral cancer pain.

Animals↗
PubMed2004

Reduced expression of hyaluronan is a strong indicator of poor survival in oral squamous cell carcinoma.

Several malignant tumours accumulate hyaluronan (HA), a matrix component suggested to promote cancer cell growth and migration. The expression and prognostic value of HA was analysed in a cohort of 151 oral squamous cell carcinoma (SCC) patients with adequate archival tumour material and follow-up data. The tumour samples were stained using a biotinylated HA-specific probe. Normal squamous epithelium showed a strong and homogeneously distributed staining for HA. The most superficial layers were HA-negative. In moderate (n=11) and high grade (n=16) dysplasias an irregular HA staining was observed around invasive cancer. Malignant transformation in oral squamous cell epithelium changed the staining toward irregular with focal reduction of HA. The well (n=92) or moderately differentiated (n=47) carcinomas had a strong HA staining intensity. In poorly differentiated tumours (n=12) the HA staining was weaker and mainly intracellular. The stromal tissue showed usually moderate (n=69) or strong (n=67) HA staining intensity with no statistically significant correlation with the degree of tumour differentiation. At the end of the follow-up (median 52 months) 66 (43%) patients had died because of an oral SCC. A significant difference in overall survival (OS) and disease free survival (DFS) (P=0.0002 and 0.0020, respectively) was noticed between the patients with the different epithelial staining patterns for HA. The reduction of HA staining was associated with poor survival. In Cox's multivariate analysis HA staining was a significant independent predictor of OS (P=0.011) and DFS (P=0.013). These results suggest that HA is a prognostic marker in oral squamous cell carcinoma.

Adolescent↗
PubMed2004

Hamsters chewing betel quid or areca nut directly show a decrease in body weight and survival rates with concomitant epithelial hyperplasia of cheek pouch.

Betel quid (BQ) chewing is strongly associated with the occurrence of oral leukoplakia, oral submucous fibrosis, and oral cancer. There are about 200-600 million BQ chewers in the world. Previous animal studies support the potential carcinogenicity of BQ in different test systems. However, little animal experiment has let hamsters or rats to chew BQ directly, similar to that in humans. In the present study, we established a hamster model of chewing BQ or areca nut (AN). A total of 81 2-week-old hamsters were randomly divided into three groups: 25 for control group, 28 for BQ-chewing group, and 28 for AN-chewing group. These animals were fed with powdered diet with/without BQ or AN for 18 months. Although the consumption of BQ or AN showed some variations, hamsters fed with powdered diet could chew and grind AN or BQ into small pieces of coarse fibers during the entire experimental period. The survival rate of AN-chewing hamsters decreased significantly after 6 months of exposure. The mean survival time was 15.6 +/- 0.9 months for control animals, 13.6 +/- 0.98 months for AN-chewing animals, and 15.7 +/- 0.55 months for BQ-chewing animals. The body weight of BQ- or AN-chewing animals also decreased after 4-13 months. Hamsters fed with AN for 18 months showed hyperkeratosis in 80% and acanthosis in 50% of cheek pouches. Animals fed with BQ for 18 months also showed hyperkeratosis in 93% and acanthosis in 14% of cheek pouches. These results indicate that AN and BQ components may induce alterations in proliferation and differentiation of oral epithelial cells. Animal model of chewing BQ or AN can be useful for future tumor initiation, promotion and chemoprevention experiments simulating the condition of BQ chewing in humans.

Animals↗
PubMed2004

The sensitivity and specificity of the OralCDx technique: evaluation of 103 cases.

In this study, we compared 103 OralCDx results with the histological findings of 96 clinical sites in 80 patients (33 females; 64.3+/-13.7 years and 47 males; 53.2+/-11.5 years). The histological findings were classified as follows: compatible with oral leukoplakia (OL; n = 60) or oral lichen planus (OLP; n = 17), both without dysplasia; dysplasia in OL or OLP (n = 9); and oral squamous cell carcinoma (OSCC; n = 17). There were seven (6.8%) specimens with an inadequate cell count. Overall, the sensitivity of the OralCDx technique to detect dysplasia and OSCC was 92.3% (95% CI: 74.9-99.1%), and the specificity was 94.3% (95% CI: 86.0-98.4%). The positive likelihood ratio (LR+) was 16.2 (95% CI: 6.2-42.1) and the negative likelihood ratio (LR-) was 0.08 (95% CI: 0.02-0.31). In conclusion, these figures are in agreement with previously published data and support the use of OralCDx as a screening tool of oral lesions, but further trials are still necessary.

Biopsy↗