Is p16(INK4a) protein expression in oral ST lesions a reliable precancerous marker?

This study correlates the expression of p16(INK4a) and p53 with the detection of high risk human papillomavirus (HPV) in three clinical grades of smokeless tobacco keratosis (STK) as compared with patients without a history of smokeless tobacco use. Tissue samples, including squamous cell carcinoma (SCC) were evaluated for the expression of p16(INK4a) and p53 by indirect immunohistochemical methods using commercially obtained antibodies. HPV DNA analysis was performed using consensus sequence polymerase chain reaction (PCR). At least focal p16(INK4a) expression was detected in Grade I, II and III STK, SCC and control samples of alveolar ridge keratoses (ARK). p16(INK4a) expression in STK and in ARK was typically weak but was relatively strong in all SCC. Strong p53 nuclear staining was detected in STK, SCC and ARK. HPV DNA was detected in Grade I, II and III STK, SCC and ARK, but did not correlate with p16(INK4a) expression. p16(INK4a) distribution did not correlate with STK grade and does not appear to be related to the detection of HPV DNA by PCR in either STK or in SCC. There is an apparent relationship between the grade of STK and the presence of HPV. HPV was rarely detected in high-grade lesions.

Proliferative verrucous leukoplakia: report of two cases and a discussion of clinicopathology.

Proliferative verrucous leukoplakia (PVL) is a recently delineated but poorly recognized form of multifocal leukoplakia that is premalignant and of unproven origin. PVL generally presents as a simple benign form of hyperkeratosis that tends to spread and become diffuse. Although slow-growing, the disease is persistent and irreversible. Clinically, PVL often presents as an exophytic wart-like form of leukoplakia that appears to be resistant to nearly all forms of therapy. PVL of the oral cavity is best-defined as a continuum of oral epithelial disease with hyperkeratosis at one end of a clinical and microscopic spectrum and verrucous carcinoma or squamous cell carcinoma at the other. The microscopic findings associated with PVL are dependent on the stage of the disease and the adequacy of the biopsy. Microscopic findings can be markedly variable. PVL is a clinicopathologic disorder that includes the microscopic entity known as verrucous hyperplasia as a component of its histopathologic progression. This article reports on two cases of PVL, describes the clinicopathology of the disease process, and presents therapeutic and etiologic considerations.

Vertical guided bone-graft augmentation in a new canine mandibular model.

Using the mandibular inferior border of four fox hounds from an extraoral approach, six high-profile Brånemark implants were placed in each animal and bone grafted. Graft materials studied included demineralized freeze-dried allograft with and without irradiation sterilization (3.8 x 10(4) Gy), corticocancellous iliac autograft, blood clot, and a control. Corticocancellous grafts were studied with and without expanded polytetrafluoroethylene (EPTFE) barriers. The barrier function improved both graft volume incorporated and bone-implant interface contact. The autograft performed better than the allograft. Irradiation of the allograft did not appear to affect graft performance. The barrier functioned to improve graft incorporation for augmentation and interface contact and gives credence to the use of barriers in conjunction with vertical augmentation grafting of jawbone.

Detection of human papillomavirus DNA in oral verrucous carcinoma by polymerase chain reaction.

Archival tissue biopsies of 17 cases of oral verrucous carcinoma were tested for human papillomaviruses by polymerase chain reaction followed by DNA slot-blot hybridization. Sections of the biopsies were also tested by in situ DNA hybridization with biotin-labeled probes for human papillomavirus types 6/11, 6/18, and 31/33/35. Using polymerase chain reaction, human papillomavirus DNA was detected in seven of 17 cases (41%). Slot-blot hybridization of the amplification products identified human papillomavirus type 6 in two cases, type 11 in four cases, and both types 6 and 11 in one case of oral verrucous carcinoma. In situ hybridization confirmed the presence of human papillomavirus type 6/11 DNA in tumor cell nuclei for each of the cases which tested positive by polymerase chain reaction and was negative in the remaining 10 cases. We conclude that human papillomavirus types 6 and 11 are frequently present in cases of oral verrucous carcinoma.

A double-blind study of topically applied 5% amlexanox in the treatment of aphthous ulcers.

A double-blind trial of amlexanox (C16H14N2O4) was carried out in 32 patients with recurrent oral aphthous ulcerations. During the treatment period, which lasted for 3 days, patients received either placebo topical paste or 5% amlexanox paste. The paste was applied by the investigator twice per day for 3 days and once on the fourth day. Efficacy was assessed by the following parameters: 1) pain measured by the patients marking a 15-cm line between poles connoting no pain versus severe pain; 2) erythema evaluated by the investigator on a four-point scale ranging from none to strong; 3) size determined by investigator measurement of the perpendicular dimensions of the ulcer; and 4) an investigator's improvement scale consisting of six rank-ordered points from -1 for worsening of the ulcer with respect to previously described criteria to +4 when the ulcer had healed completely. All evaluations were based on a comparison with the day 1 visit of the patient. Outcomes for patients receiving the active ingredient were superior on all four criteria of effectiveness. Group differences for all criteria but pain reduction were statistically significant (P < .05). No side effects were reported. It was concluded that amlexanox is effective in reducing aphthous ulcer erythema, pain, and lesional size.

Human gingival tissue response to HTR polymer.

Biopsies secured during reentry surgical evaluation of previously treated periodontal osseous defects were examined for gingival tissue response to HTR polymer. Eleven patients provided biopsies of HTR grafted sites 6-7 months after initial implantation. Minimal inflammation and infrequent foreign body giant cells were found. Bone was present in about half of the samples and osteogenesis associated with the HTR graft material was seen in about 20% of the biopsies. Serendipitously, biopsies of other graft materials or debridement only sites from 6-30 months post-treatment were also available for analysis and comparison, and showed similar tissue response. The results of this study suggest that HTR polymer (and other graft materials) is very biocompatible and elicits no untoward gingival tissue responses when placed in periodontal osseous defects.

Detection of human papillomavirus DNA by in situ DNA hybridization and polymerase chain reaction in premalignant and malignant oral lesions.

The sensitivity of detection of human papillomavirus (HPV) DNA in premalignant and malignant oral lesions by in situ hybridization (ISH) and polymerase chain reaction (PCR) were compared. With both methods HPV DNA was found in 4 of 24 cases of epithelial dysplasia, 4 of 14 cases of verrucous hyperplasia, and 1 of 10 cases of squamous cell carcinoma. The 10 cases of smokeless tobacco keratoses and 3 cases of verrucous carcinoma that we examined were all negative for HPV DNA. The PCR for the E6 open reading frame of HPV-16 correctly identified all cases that were positive by ISH. Only a single case that was positive by PCR was negative by ISH for HPV DNA. However, the PCR demonstrated the presence of HPV-16 infection in one case, which had hybridized most intensely with the probe for types 31/33/35 in the ISH. This discrepancy probably is due to the high degree of cross-hybridization in the ISH assay. PCR appears to be an effective technique for identifying HPV-16 DNA sequences in biopsy material from premalignant and malignant oral lesions.

Detection of human papillomavirus-genomic DNA in oral epithelial dysplasias, oral smokeless tobacco-associated leukoplakias, and epithelial malignancies.

Human papillomavirus (HPV) is an infectious agent that is increasingly associated with mucosal cancers, in particular cancer of the cervix. The present investigation was undertaken in an attempt to determine whether HPV could be easily detected in biopsies of oral tissues, specifically oral squamous cell carcinomas, oral epithelial dysplasias, smokeless tobacco keratoses, verrucous hyperplasia, and verrucous carcinoma. In situ DNA hybridization methods were used to isolate specific HPV genomes. Among 100 instances of benign leukoplakia, only 4% of non-tobacco-related and 10% of smokeless tobacco-related lesions harbored viral sequences. We were able to detect viral sequences in dysplastic lesions 3% of the time. Alternatively, 17% and 20% of the verrucous hyperplasias and verrucous carcinomas were positive for viral nucleic acids. Six percent of the squamous cell carcinomas harbored HPV. On the basis of these findings, it is concluded that HPV of known genotype can be identified in oral premalignant and malignant neoplasms.

Periosteal osteosarcoma of the maxilla: a case report and review of literature.

Juxtacortical osteosarcomas, including periosteal and parosteal subtypes, are uncommon neoplasms of the jaws. In long bones, the biologic behavior of the periosteal variant is reported to be more aggressive than the parosteal tumor. Juxtacortical osteosarcoma of the jaws appears to have a slightly more favorable prognosis than in long bones, although a larger series of cases needs to be evaluated before a definitive conclusion concerning the behavior of juxtacortical osteosarcoma of the jaws can be made.

Evaluation of oral and laryngeal specimens for human papillomavirus (HPV) DNA by dot blot hybridization.

Human papillomavirus (HPV) is an infectious agent which is increasingly associated with mucosal cancers, in particular, cancer of the cervix. The present investigation was undertaken in an attempt to determine whether the Virapap human papillomavirus (HPV) DNA detection kit, originally designed for identification of HPV in exfoliated cervical cells could be employed in detection of HPV in biopsies of oral and laryngeal tissue samples, specifically oral squamous cell carcinomas, epithelial dysplasias, smokeless tobacco keratoses, and laryngeal papillomatosis. The ViraPap HPV DNA detection assay was found to be useful for HPV DNA identification in tissue samples from oral and laryngeal specimens.

Focal dermal hypoplasia. Current concepts and differential diagnosis.

Focal dermal hypoplasia syndrome (FDH) is a congenital disorder of mesodermal derivation with some ectodermal participation. The disorder, first described in 1962, is characterized by tenacious defects consisting of thinning of the skin; herniations of adipose tissue; abnormal skin pigmentation and other skeletal, dental, ocular, hair, and nail abnormalities. A rare instance of focal dermal hypoplasia syndrome is reported as characterized by papillary gingival hyperplasia. Differential diagnostic guidelines that separate focal dermal hypoplasia from a host of other skin and mucous membrane disorders are discussed along with therapeutic modalities and the possible relationship of human papillomavirus to focal dermal hypoplasia syndrome.

Oral evaluation of patients with chemosensory disorders.

The physical examination of the patient with dysgeusia must include a thorough intraoral examination. Although the initial screening examination may be performed by clinicians of various disciplines, specialized intraoral or dental examination may be required to diagnose and manage the dysfunction.

A report of two smokeless tobacco surveys and associated intervention strategies among Utah adolescents.

Smokeless tobacco is an increasingly popular substance, especially among male adolescents. We determined the prevalence of smokeless tobacco use and evaluated selected factors associated with it among 8,902 students in grades 7 through 12 in the Davis County, Utah, School District. The students responded anonymously in their classrooms to a 16-item self-reporting questionnaire. Results indicated that smokeless tobacco usage was predominately a male phenomenon in all grades and schools, as illustrated by prevalence rates "within the past week" for junior high school students (male: 15.0%; female: 1.1%). Modal responses regarding users' source of supply revealed "friends" as the leading source for junior high students (43.1%) and direct purchase for senior high students (62.2%). Peer usage or nonusage of smokeless tobacco was found to be directly and proportionately correlated with smokeless tobacco users' participation in the school activity designated "sports" for both junior high (39%) and senior high school students (36.2%). Subsequently, clinical evaluation of high school male athletes was undertaken. To our surprise, the rate of lesion detection among members of this group, previously judged to be the subjects most likely to use smokeless tobacco, fell far short of the anticipated rate. We believe the reason for the low rate may be the result of numerous efforts to educate students and coaches, the reinforcement of existing tobacco use policies by the Davis County School District, and the reiteration to smokeless tobacco vendors of the terms of the Utah laws relative to smokeless tobacco sales. This health-endangering behavior deserves a concerted educational thrust by health professional, parents, and teachers, with emphasis on prevention.

Effectiveness of video instruction in educating teenagers about the health risks of smokeless tobacco use.

Smokeless tobacco use, especially among adolescents, appears to have gained increased recent popularity. A resurgence in the use of this product was identified in the mid-1970s. Surveys in the United States have documented that between 8% and 30% of all high school males are regular users of smokeless tobacco products. Investigators have identified specific clinical lesions associated with smokeless tobacco use that appear most frequently as wrinkled mucosal surfaces with delicate white stria. Such lesions have been termed smokeless tobacco keratoses. Gingival inflammation and periodontal inflammation have also been associated with the use of this product. The purpose of the current investigation was to determine the effectiveness of a specific intervention aid, video instruction, for providing teenagers with information concerning the health risk of smokeless tobacco use. The video provided new information to students and appeared to be an effective tool for student health education. It is, however, unclear at this point how well the information will be retained or whether or not viewing the videotape will encourage the student to reconsider the habit and decrease the likelihood that he or she will begin or continue it. These aspects and the long-term impact of the video instruction need to be addressed by a longitudinally designed study and future research on smokeless tobacco use among teenagers.

Morphologic and immunohistochemical evidence of human papillomavirus capsid antigen in smokeless tobacco keratoses from juveniles and adults.

Seventy-seven tissue samples from patients with either degree I, II, or III smokeless tobacco keratoses were examined. The tissues were evaluated for the presence of human papillomavirus (HPV) antigen by immunocytochemical staining. Capsid antigen could be identified in sixteen cases (20.78%). This investigation further supports the concept that smokeless tobacco-associated leukoplakias can be correlated with HPV infection.

Botryoid odontogenic cyst: clinicopathologic analysis of ten cases with three recurrences.

The botryoid odontogenic cyst (BOC) is a rare cyst of odontogenic origin originally described in 1973 by Weathers and Waldron as a variant of the lateral periodontal cyst. Ten examples of this rare lesion were studied by light and electron microscopy and the clinical and radiographic findings were analyzed. Eight of ten lesions were located in the mandible; the anterior mandible being the dominant site. Five of the ten lesions were unilocular, the largest measuring 4.5 X 1.2 cm. Only two of the ten botryoid odontogenic cysts were radiographically multilocular. Three lesions represented recurrences 8, 10, and 10 years after previous surgical intervention. All patients were white with an average age of 46 years. Perhaps the most significant information gained from this investigation of botryoid odontogenic cysts is the fact three of ten lesions recurred after initial surgical removal. It is important that practitioners take note of the fact that: 1) a recurrence potential may exist for the botryoid odontogenic cyst that has gone unrecognized, 2) recurrence may not occur until a decade after initial surgery, and 3) lesions may occasionally become destructive.

Necrotizing sialometaplasia obscuring an underlying malignancy: report of a case.

Necrotizing sialometaplasia poses many diagnostic problems, both clinically and microscopically. Caution had most frequently been urged for distinguishing between malignancy and NS, so as to avoid mutilating surgical treatment resulting from the misdiagnosis of a lesion that is benign and self-limiting. This case has been presented to alert the practitioner to the possibility that NS may obscure an underlying malignant disease process, possibly resulting in delays in referral or treatment. The exceedingly rapid growth of this mesenchymal neoplasm may have caused obstruction of the blood supply to the overlying mucosa and submucosa, thereby producing the ischemic alterations observed in the first biopsy specimens. Some of the difficulties encountered in the detection and diagnosis of neoplasms arising in the parapharyngeal space were discussed, and some previously published suggestions to aid in these efforts were reiterated.