HPV-16 in a distinct subset of oral epithelial dysplasia.

Human papillomavirus (HPV) 16 is the most common high-risk HPV type identified in oropharyngeal and cervical neoplasia. Recently, HPV-associated oral epithelial dysplasia with specific histopathologic features and demographics similar to HPV-oropharyngeal carcinoma has been identified. The objective of this study was to evaluate histopathologically all cases of HPV-oral epithelial dysplasia seen in one center and identify HPV types in a subset of cases. Cases with specific histopathology for HPV-oral epithelial dysplasia that were positive both by immunohistochemical studies for p16 and by in situ hybridization for high-risk types of HPV were further analyzed using QIAamp DNA Tissue Kits (Qiagen, Hilden, Germany). DNA was extracted, amplified, and digested with restriction enzymes and run on a polyacrylamide gel. Digestion patterns were visually compared with a database of known HPV digestion patterns for identification. There were 53 specimens included in the analysis. There were 47 males and six females (7.8:1), with a median age of 55 years (range 41-81). The most common site of involvement was the tongue/floor of mouth (77% of cases). Of the 53 cases, 94% exhibited parakeratosis and/or hyperkeratosis. All the cases featured karyorrhexis, apoptosis, and characteristics of conventional carcinoma in situ. The quantity of DNA extracted was sufficient for analysis in 22 cases. HPV-16 was identified in 20/22 (91%) cases. One case was associated with HPV-33 and one with HPV-58 (5% each). Eight of the 53 cases (15%) were associated with invasive squamous cell carcinomas.

Human papillomavirus-associated oral intraepithelial neoplasia.

This study evaluated an unusual subset of oral epithelial dysplasia for the presence of transcriptionally active high-risk HPV subtypes and to further characterize the histological criteria for this condition. There were 20 cases diagnosed as epithelial dysplasia with marked apoptosis of the anterior oral cavity. Clinical and follow-up data were collected and histopathological features were documented. Immunoperoxidase studies were performed for p16 and in situ hybridization studies were performed for low- and high-risk HPV sub-types. Gender- and site-matched controls of conventional moderate-to-severe oral epithelial dysplasia were similarly evaluated using immunoperoxidase studies for p16 and in situ hybridization; the number of apoptotic cells for study and control cases was counted at two different tissue sites. There were 17 men and 3 women with a median age of 56 years. Seventeen lesions were described as white and five were described as rough or papillary. Thirteen were located on the lateral or ventral tongue, some extending onto the floor of the mouth. Epithelial hyperplasia with marked karyorrhexis and apoptosis were present in all the cases, along with features of conventional oral epithelial dysplasia. A statistically significant number of apoptotic cells were identified in the study cases when compared with controls (P>0.0001). Twenty cases were positive for high-risk HPV by in situ hybridization and all 19 nineteen cases evaluated for p16 demonstrated overexpression. Two patients were diagnosed with squamous cell carcinomas and one patient developed recurrent disease. We report a subset of oral epithelial dysplasia that occurs mostly in adult men on the ventral or lateral tongue and is positive for high-risk HPV and for p16. We propose use of the term 'HPV-associated Oral Intraepithelial Neoplasia' to characterize these lesions of the oral cavity for consistency in nomenclature with HPV-associated lesions of the lower anogenital tract. One case recurred and one developed invasive cancer.

Safety assessment of oral photodynamic therapy in rats.

Photodynamic therapy (PDT) is based on the synergism of a photosensitive drug (a photosensitizer) and visible light to destroy target cells (e.g., malignant, premalignant, or bacterial cells). The aim of this study was to investigate the response of normal rat tongue mucosa to PDT following the topical application of hematoporphyrin derivative (Photogem®), Photodithazine®, methylene blue (MB), and poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with MB. One hundred and thirty three rats were randomly divided in various groups: the PDT groups were treated with the photosensitizers for 10 min followed by exposure to red light. Those in control groups received neither photosensitizer nor light, and they were subjected to light exposure alone or to photosensitizer alone. Fluorescent signals were obtained from tongue tissue immediately after the topical application of photosensitizers and 24 h following PDT. Histological changes were evaluated at baseline and at 1, 3, 7, and 15 days post-PDT treatment. Fluorescence was detected immediately after the application of the photosensitizers, but not 24 h following PDT. Histology revealed intact mucosa in all experimental groups at all evaluation time points. The results suggest that there is a therapeutic window where PDT with Photogem®, Photodithazine®, MB, and MB-loaded PLGA nanoparticles could safely target oral pathogenic bacteria without damaging normal oral tissue.

Pain Management for Dental Medicine in 2021: Opioids, Coronavirus and Beyond.

Over the past year our attention has inevitably been on the coronavirus pandemic, the health and welfare of our families, patients, and office staffs as well as the re-opening of our dental practices. In addition, the opioid crisis continues, is very likely to worsen as a result of the pandemic and continues to be a challenge to Dentistry. National public health issues and healthcare disparities continue and have created a global concern for providing evidence-based, adequate pain management in the dental setting. We have brought together a group of national thought leaders and experts in this field who will share their insights on the current state of opioid prescribing in Dentistry and describe some of the exciting work being done in advancing pain management. The learning objectives for this conference proceedings were: Describing the implications of current public health concerns for safe and effective pain management in dental medicine.Identifying risk factors and understanding the current guidelines for the use of opioid and non-opioid medications in dental medicine.Analyzing the interprofessional collaborations necessary for effective pain management in dental medicine.Recognizing the challenges and opportunities brought about by the COVID-19 pandemic for the dental profession.Applying evidence-based strategies for managing the complex pain patient in the dental setting.Appraising new and future modalities for the assessment and management of orofacial pain.

Management of oral infections in cancer patients.

The myelosuppressive and mucosal-damaging consequences of cancer and cancer therapies place patients at high risk for developing infectious complications. Bacterial, fungal, and viral infections are all commonly encountered in the oral cavity, contributing to both morbidity and mortality in this patient population. Prevention, early and definitive diagnosis, and appropriate management are critical to ensure optimal treatment outcomes. With the majority of cancer patients treated as outpatients in the community setting, oral health care professionals play an important role in managing such infectious complications of cancer therapy.

Topical Clonazepam Solution for the Management of Burning Mouth Syndrome: A Retrospective Study.

AIMS: To evaluate and compare the effectiveness of two concentrations of topical clonazepam solution in improving symptoms of burning mouth syndrome (BMS). METHODS: A retrospective chart review was conducted of patients diagnosed with BMS and managed with topical clonazepam solution between 2008 and 2015. A 0.5-mg/mL solution was prescribed until 2012, when this was changed to a 0.1 mg/mL solution. Patients were instructed to swish with 5 mL for 5 minutes and spit two to four times daily. The efficacies of the two concentrations were compared using patient-reported outcome measures at the first follow-up, including the reported percentage of improvement in burning symptoms and the change in burning severity from baseline ranked on an 11-point numeric rating scale (NRS). Response to treatment was compared between the two concentrations using Wilcoxon rank sum test. RESULTS: A total of 57 subjects were included, 32 in the 0.1-mg/mL cohort and 25 in the 0.5-mg/mL cohort, and evaluated at a median follow-up of 7 weeks. The median overall percentage improvement was 32.5% in the 0.1-mg/mL cohort and 75% in the 0.5-mg/mL cohort. The median reduction in NRS score was 0.5 points in the 0.1-mg/mL cohort and 6 points in the 0.5-mg/mL cohort. The use of either outcome measure revealed that the response to treatment with the 0.5-mg/mL solution was superior to that of the 0.1 mg/mL solution (P < .01). CONCLUSION: These findings suggest that a 0.5-mg/mL topical clonazepam solution is effective in the management of BMS. Future randomized clinical trials are warranted.

Safety and tolerability of topical clonazepam solution for management of oral dysesthesia.

OBJECTIVES: The aim of the study was to determine the absolute and relative safety of treatment with 2 concentrations of topical clonazepam solution (0.1 mg/mL, 0.5 mg/mL) for management of oral dysesthesia. STUDY DESIGN: The study was a retrospective chart review of patients diagnosed with oral dysesthesia and managed with topical clonazepam solution (swish and spit) between 2008 and 2015. The relative safety of the 2 concentrations was evaluated in terms of occurrence of adverse drug reactions (ADRs) and occurrence of change to treatment plan secondary to ADRs. RESULTS: For the study, 162 patients were included-84 patients in the 0.1 mg/mL cohort and 78 in the 0.5 mg/mL cohort, who were evaluated for a median follow-up period of 6 weeks. Thirty-eight (23%) patients developed ADRs. The most frequently reported ADR was sedation (62% of ADRs), followed by altered mental status and dizziness (7% each). Dose adjustments were required in 9 patients (6%) and treatment discontinuation in 13 (8%). ADRs were more frequently reported in the 0.5 mg/mL cohort, but no significant difference was found in terms of occurrence of ADRs, change to treatment plan secondary to ADRs, or types of ADRs (P > .05). CONCLUSIONS: Treatment with topical clonazepam solution in either 0.5 mg/mL or 0.1 mg/mL concentration appears to be safe and well-tolerated. Future prospective studies are needed to confirm this finding.

Oral Medicine referrals at a hospital-based practice in the United States.

OBJECTIVE: The objective of this study was to characterize the outpatient oral medicine (OM) clinic at Brigham and Women's Hospital (BWH), with particular emphasis on patient demographic characteristics and referral patterns. MATERIALS AND METHODS: A retrospective case record review of all initial consultations with OM experts at BWH from 2008 to 2010 was conducted. Data included demographic information, type of medical insurance, reason for referral, referring doctor's specialty, and distance between the patient's home and the referring doctor as well as BWH, number of prior doctors seen for the presenting problem (per patient report), tests ordered at the consultation visit, and clinical diagnoses. RESULTS: There were 1043 new outpatient consultation visits. Patients lived a median distance of 9.5 miles from the referring doctor and 18.9 miles from BWH and saw a median of one doctor (range 0-9) before consultation. Two thirds of patients were referred by physicians. The most common diagnoses included immune-mediated mucosal conditions (27.2%), orofacial pain disorders (25.1%), benign tumors or neoplasms (10.3%), and dysplasia and cancerous conditions (7.6%). Biopsy was the most frequent test performed at consultation. CONCLUSIONS: Patients with oral conditions often see more than one doctor, before being referred to an OM expert and typically travel twice the distance to the expert compared with that between their home and the referring doctor. Equal efforts should be made to increase awareness of the importance of the specialty of OM among dentists, physicians, and the public.

Granulomatous foreign body reaction to dermal cosmetic fillers with intraoral migration.

OBJECTIVE: We report intraoral granulomatous foreign body reactions in patients treated with calcium hydroxylapatite (CHA) or poly-l-lactic acid (PLA). STUDY DESIGN: Clinical and histopathologic data were obtained from 25 patients who developed orofacial nodules or swelling after dermal filler injections. RESULTS: All 25 patients were women aged 35 to 78 years (median, 55 years). All had a history of injection of CHA (n = 13) or PLA (n = 12) to the lips, nasolabial area, or mental area. Two patients developed cutaneous nodules at the sites of injections; all others presented with intraoral nodules (labial/buccal or vestibular mucosa) distant from the site of injections, suggestive of filler migration. Five of 21 cases presented with pain. Histopathologically, CHA presented as a diffuse mass of mauve-gray or beige, nonrefractile spherules, and PLA as rice- or spindle-shaped, geometric, refractile bodies within circumscribed nodules. CONCLUSIONS: Cutaneous injections of CHA and PLA fillers may induce granulomatous reactions presenting as intraoral nodules distant from the injection sites.

Localized mandibular enlargement in end-stage renal disease: two case reports and a review of the literature.

Enlargement of the jaws is an infrequently reported complication of chronic kidney disease mineral and bone disorder (CKD-MBD). Two cases of localized mandibular swellings in young patients with histories of end-stage renal disease are discussed with a review of the literature. Although 17 of the first 19 cases that were reported exhibited diffuse enlargement, these reports increase the number of localized swellings to 8 and support the contention that localized expansion of the jaws as a manifestation of CKD-MBD is more common than originally recognized.

Bony changes in the jaws of rats treated with zoledronic acid and dexamethasone before dental extractions mimic bisphosphonate-related osteonecrosis in cancer patients.

Osteonecrosis of the jaw is associated with aminobisphosphonate use in patients treated with intravenous doses for the prevention of bony metastases. A more complete understanding of the natural history of bisphosphonate-related osteonecrosis of the jaws (BRONJ), factors associated with risk, and its pathobiology has been limited by the availability of human material and the absence of clinical predictability. We now describe an animal model, developed in female Sprague-Dawley rats, in which we replicate many of the clinical, radiographic, and histologic features described in humans. Animals treated with a sequence of zoledronic acid (ZA) and dexamethosone (DX) over a one to three week period developed BRONJ-like changes following extraction of mandibular or maxillary molars. Whereas the extraction sites of control animals underwent predictable healing with rapid epithelialization, animals treated with ZA/DX demonstrated clinical and histological evidence of ulceration overlying areas of necrotic bone. In contrast to images from control animals, radiographs from animals treated with ZA/DX demonstrated poor definition of the alveolar ridge with mixed radiodensity. Modest increases in the extent of the inflammatory infiltrate were seen fourteen days after extraction in ZA-only treated animals compared to control or ZA/DX-treated rats. However, by post-extraction day 28, no differences were observed. Tissue vascularity was most pronounced in ZA-only treated animals compared to ZA/DX or control specimens. Apoptosis of epithelial cells was not observed in any experimental groups, and no evidence of Actinomyces was observed as determined by Periodic Acid Schiff (PAS) staining. The administration of ZA/DX preceding dental extractions in rats therefore results in the development of bony and soft tissue changes that are similar to those noted humans who develop BRONJ, and may provide a useful model for study of its pathogenesis, as well as strategies for its prevention and treatment.