Imiquimod for the treatment of oral leukoplakia: A two-center retrospective study.

OBJECTIVES: We aimed to assess the effectiveness of the use of topical imiquimod for the management of oral leukoplakia (OL). METHODS: This was a retrospective study. Medical chart reviews were conducted to identify patients with biopsy-proven OL treated with topical 5% imiquimod. Data included OL characteristics, histopathological diagnosis, treatment outcome, and adverse events (AEs). Treatment response was assessed by measuring the percentage reduction in the size of OL lesions. RESULTS: 33 patients (51.5% females; median age: 65 years) with 38 lesions were included. OLs were either localized (23.7%) or multifocal lesions (76.3%), with the majority on the gingiva (86.8%). Pretreatment histopathological diagnoses were dysplasia in 84.2% and nonreactive hyperkeratosis in 15.8%. Most regimens consisted of 60-minute applications, 5-days-a-week, for 6 weeks. At the end of treatment, 81.6% of 38 lesions showed a reduction in size with 68.4% exhibiting ≥50% reduction in size, and 42.1% exhibiting complete resolution. Application site reactions were the most common with pain/soreness/sensitivity occurring in 86.8%. Fatigue was the most frequently reported systemic AE (28.9%). CONCLUSION: Two-thirds of OL lesions had ≥50% reduction in size. Most AEs were temporary and resolved upon treatment discontinuation. Prospective studies are needed to further assess Imiquimod's effectiveness in OL management.

Nivolumab for Patients With High-Risk Oral Leukoplakia: A Nonrandomized Controlled Trial.

Importance: Proliferative verrucous leukoplakia (PVL) is an aggressive oral precancerous disease characterized by a high risk of transformation to invasive oral squamous cell carcinoma (OSCC), and no therapies have been shown to affect its natural history. A recent study of the PVL immune landscape revealed a cytotoxic T-cell-rich microenvironment, providing strong rationale to investigate immune checkpoint therapy. Objective: To determine the safety and clinical activity of anti-programmed cell death 1 protein (PD-1) therapy to treat high-risk PVL. Design, Setting, and Participants: This nonrandomized, open-label, phase 2 clinical trial was conducted from January 2019 to December 2021 at a single academic medical center; median (range) follow-up was 21.1 (5.4-43.6) months. Participants were a population-based sample of patients with PVL (multifocal, contiguous, or a single lesion ≥4 cm with any degree of dysplasia). Intervention: Patients underwent pretreatment biopsy (1-3 sites) and then received 4 doses of nivolumab (480 mg intravenously) every 28 days, followed by rebiopsy and intraoral photographs at each visit. Main Outcomes and Measures: The primary end point was the change in composite score (size and degree of dysplasia) from before to after treatment (major response [MR]: >80% decrease in score; partial response: 40%-80% decrease). Secondary analyses included immune-related adverse events, cancer-free survival (CFS), PD-1 ligand 1 (PD-L1) expression, 9p21.3 deletion, and other exploratory immunologic and genomic associations of response. Results: A total of 33 patients were enrolled (median [range] age, 63 [32-80] years; 18 [55%] were female), including 8 (24%) with previously resected early-stage OSCC. Twelve patients (36%) (95% CI, 20.4%-54.8%) had a response by composite score (3 MRs [9%]), 4 had progressive disease (>10% composite score increase, or cancer). Nine patients (27%) developed OSCC during the trial, with a 2-year CFS of 73% (95% CI, 53%-86%). Two patients (6%) discontinued because of toxic effects; 7 (21%) experienced grade 3 to 4 immune-related adverse events. PD-L1 combined positive scores were not associated with response or CFS. Of 20 whole-exome sequenced patients, all 6 patients who had progression to OSCC after nivolumab treatment exhibited 9p21.3 somatic copy-number loss on pretreatment biopsy, while only 4 of the 14 patients (29%) who did not develop OSCC had 9p21.3 loss. Conclusions and Relevance: This immune checkpoint therapy precancer nonrandomized clinical trial met its prespecified response end point, suggesting potential clinical activity for nivolumab in high-risk PVL. Findings identified immunogenomic associations to inform future trials in this precancerous disease with unmet medical need that has been difficult to study. Trial Registration: ClinicalTrials.gov Identifier: NCT03692325.

Use of oral devices in the management of oral dysesthesia: case reports and literature review.

Oral dysesthesia (OD) is a diagnosis of exclusion that manifests as an unpleasant and abnormal sensation of the oral mucosa without any noticeable oral lesions. Burning sensation is one of the manifestations of OD which may advocate for similar pharmacotherapeutic options to burning mouth syndrome (BMS), resulting in possible adverse events. The aim of these case reports was to illustrate the significance and rationale for the use of oral devices as a mechanical/physical barrier and a safe approach in the management of OD, without experiencing any antagonistic effects from pharmacotherapeutic agents. Two patients with spontaneous and evoked (following dental procedures) OD symptoms in the right posterior mandibular quadrant and anterior hard palatal areas were evaluated. Additionally, their OD symptoms were associated with hyposalivation and taste changes. A thorough history and complete head and neck examination, with the exclusion of oral lesions and systemic conditions, were performed. These patients were previously prescribed topical clonazepam rinses. An in-office trial, with application of orthodontic wax to the affected area, was performed as a preliminary test in order to justify the fabrication of an oral device for possible symptomatic relief. Conclusion: The case reports demonstrated significant improvement of OD symptoms and amelioration of pain following fabrication of oral devices in two patients with no undesirable effects from pharmacotherapy. Additionally, the oral devices aided as a mechanical/physical barrier, potentially exerting a placebo effect while facilitating an improved quality of life. Furthermore, the cost-effectiveness and ease of fabricating the oral device has been advantageous over other systemic medications. This encourages the need for a detailed prospective study.

Immune checkpoint inhibitors in cancer therapy: Review of orofacial adverse events and role of the oral healthcare provider.

Immune checkpoint inhibitors (ICIs) are a revolutionary class of antineoplastic therapy that restore anti-tumor immunity. Consequences of this enhanced immune response include a multitude of immune related adverse events (irAEs) that can affect any body system, including the mouth. Orofacial irAEs reproduce features of numerous immune-mediated conditions, including oral lichen planus, mucous membrane pemphigoid, and Sjögren syndrome, among others. The aim of this review is to summarize known orofacial irAEs and to familiarize oral healthcare providers with how to identify and manage these toxicities as part of the care team for patients treated with ICIs.

Oral lichen planus: comparative efficacy and treatment costs-a systematic review.

OBJECTIVE: To compare the reported efficacy and costs of available interventions used for the management of oral lichen planus (OLP). MATERIALS AND METHODS: A systematic literature search was performed from database inception until March 2021 in MEDLINE via PubMed and the Cochrane library following PRISMA guidelines. Only randomized controlled trials (RCT) comparing an active intervention with placebo or different active interventions for OLP management were considered. RESULTS: Seventy (70) RCTs were included. The majority of evidence suggested efficacy of topical steroids (dexamethasone, clobetasol, fluocinonide, triamcinolone), topical calcineurin inhibitors (tacrolimus, pimecrolimus, cyclosporine), topical retinoids, intra-lesional triamcinolone, aloe-vera gel, photodynamic therapy, and low-level laser therapies for OLP management. Based on the estimated cost per month and evidence for efficacy and side-effects, topical steroids (fluocinonide > dexamethasone > clobetasol > triamcinolone) appear to be more cost-effective than topical calcineurin inhibitors (tacrolimus > pimecrolimus > cyclosporine) followed by intra-lesional triamcinolone. CONCLUSION: Of common treatment regimens for OLP, topical steroids appear to be the most economical and efficacious option followed by topical calcineurin inhibitors. Large-scale multi-modality, prospective trials in which head-to-head comparisons interventions are compared are required to definitely assess the cost-effectiveness of OLP treatments.

Oral manifestations of immune-related adverse events in cancer patients treated with immune checkpoint inhibitors.

Immunotherapy with immune checkpoint inhibitors (ICIs) has transformed cancer treatment over the past decade, improving survival rates in numerous advanced cancers. Immune-related adverse events (irAEs) are common and can affect any organ system, with many of these toxicities being well-characterized with clear grading criteria and management approaches. There has been less emphasis on oral manifestations of irAEs. This review provides an overview of oral manifestations of irAEs, including mucosal and salivary gland toxicities, and proposes a grading system and management guidelines. irAEs are common treatment-related toxicities in patients treated with ICIs. Oral irAEs can range from asymptomatic white reticulations to life-threatening mucocutaneous reactions requiring aggressive management with corticosteroids and/or permanent discontinuation of ICIs. Oral healthcare providers should be prepared to identify and manage oral irAEs in collaboration with oncologists and other specialists.

Oral manifestations, salivary flow rates and Candida species in Thai HIV-infected patients.

BACKGROUND: Effects of various Highly Active Antiretroviral Therapy (HAART) regimens on oral heath are unclear. Objectives: We aimed to evaluate effects of HAART on oral manifestations, salivary flow rates (SFR) and Candida species in HIV-infected patients who took mostly non-protease inhibitor-based HAART regimens. MATERIAL AND METHODS: A cross-sectional study was performed on HIV-infected patients taking and never taken HAART who attended Thai Red Cross AIDS Research Centre (n = 48). Non-HIV subjects were recruited as control (n = 20). Oral conditions and salivary flow rates were evaluated using oral examination and measurement of unstimulated and stimulated saliva. In addition, Candida colonization counts (colony forming units; CFUs) and Candida species from the collected saliva were evaluated using CHROMagar. RESULTS: The most common oral manifestation in HIV-infected subjects taking HAART was hyperpigmentation. Unstimulated and stimulated SFR among the three groups were not statistically significant. Candida colonization was detected in 64%, 65% and 35% of HIV-infected subjects taking HAART, HAART-naïve, and non-HIV subjects, respectively. While 20% and 35% of HIV-infected subjects with and without HAART, respectively, had Candida CFUs higher than 500/ml, all non-HIV carriers had Candida CFUs lower than 500/ml. The most common Candida colonization species was C. albicans in HAART and non-HIV groups. Interestingly, HAART-naïve group was colonized more by non-albicans species. CONCLUSIONS: HAART has minimal effects on oral health. While HAART may not prevent Candida colonization, it might lead to reduction of non-albicans species. Because maintaining low Candida counts is important, HAART administration and antifungal sensitivity test should be considered in HIV-infected patients. Key words:HIV, Candida, HAART, Oral manifestation, Salivary flow rates.

Influence of oral moisturizing jelly as a saliva substitute for the relief of xerostomia in elderly patients with hypertension and diabetes mellitus.

Dry mouth is common in elderly patients. However, the use of saliva substitute has been limited due to its inedibility. This study investigated the efficacy of oral moisturizing jelly (OMJ), a novel edible saliva substitute. A pre-post design was conducted in 118 elderly patients diagnosed with hypertension and/or diabetes mellitus. After using OMJ, signs and symptoms of dry mouth were compared with baseline data. The properties of saliva were compared between the OMJ use and non-use periods. The use of OMJ for 2 weeks significantly reduced symptoms of dry mouth, while the use for 1 month reduced the signs of xerostomia, prevented the decline of salivary pH(s) and improved buffering capacities. OMJ was equally effective in patients taking 1 to 2 and 3 to 7 medications. Furthermore, 65% of patients preferred OMJ over a commercial product. OMJ could be new edible saliva substitute for elderly patients suffering from dry mouth. Clinicaltrials.gov ID: NCT02317172.

Higher prevalence of oral human papillomavirus infection in HIV-positive than HIV-negative Thai men and women.

OBJECTIVE: This study was designed to investigate the prevalence of oral human papillomavirus (HPV) infection among HIV-positive and HIV-negative Thai men and women. METHODS: Participants including men who have sex with men (MSM) and heterosexual women were enrolled at the Thai Red Cross Anonymous Clinic in Bangkok. History taking and oral examination were performed by three independent dentists after calibration. HPV infection was evaluated from oral rinse with mouthwash collected at the time of examination. HPV typing was performed by PCR and nucleic acid hybridization to detect thirty-seven HPV DNA genotypes using Linear Array(®) HPV Genotyping Test (Roche Molecular System, Inc.). RESULTS: 244 subjects were enrolled in the study, consisted of 187 HIV-positive (51.9% women and 48.1% MSM) and 57 HIV-negative (21.0% women and 79.0% MSM) Thai subjects. The prevalence of oral HPV infection was 17.2% in HIV-positive subjects whereas only 5.3% of HIV-negative cases had HPV detected in their oral rinses (p=0.0346). Among HIV positive subjects, MSM had higher chance of having HPV infection than females (25% vs. 9.4%, p=0.0074). CONCLUSIONS: HIV-positive Thai MSM and women had higher prevalence of oral HPV infection than those without HIV.

Thai dental practitioners' knowledge and attitudes regarding patients with HIV.

To investigate the knowledge and attitudes of Thai dental practitioners regarding patients with HIV, a cross-sectional study using self-administered questionnaires was conducted. The questionnaires requested demographic information and included questions evaluating the knowledge and attitude of dental practitioners towards HIV. The results were analyzed using Scheffe method for multiple comparisons at the 95 percent confidence level. Out of 1,200 questionnaires sent, 446 questionnaires were returned (response rate 37.2 percent). The subjects included final (sixth)-year dental students (11.9 percent), general dentists (29.1 percent), specialist dentists (15.5 percent), dental hygienists (30.5 percent), and dental assistants (13 percent). More than 80 percent of the dental practitioners correctly answered the questions testing their basic knowledge of HIV such as routes of transmission and common opportunistic infections. However, knowledge about HIV pathogenesis, complications, and advances in HIV management was lacking. Dental hygienists and dental assistants had statistically significant lower scores in knowledge about HIV than other groups. Sixty-seven percent of dental practitioners said they feel worried when treating patients with HIV, and 20.4 percent said they would deny treatment for patients with HIV if possible. While knowledge about HIV may be adequate among dental practitioners in Thailand, greater effort should be put into emphasizing positive attitudes towards patients with HIV.

Perceived dental needs and attitudes toward dental treatments in HIV-infected Thais.

Despite the advancement in highly active antiretroviral therapy and improved health status of HIV-infected individuals, dental problems are still affecting their life and well-beings. We aimed to establish the prevalence of oral and dental complaints among HIV-infected patients, the prevalence of delayed access to dental service, and factors related with delayed access to dental service. A cross-sectional study using self-report questionnaire completed by the HIV-positive subjects was conducted at the largest HIV research clinic in Thailand during 2009-2010. Of all 299 subjects (28.6% males, 71% females, and 0.4% sex change from male to female: ages ranged from 22 to 59 years [mean 36.7±5.53)]), 84.3% reported of having past or present illnesses or problems related to the dental or oral conditions. The most reported problems were dental hypersensitivity (93.3%), bleeding from the gum (92.1%), and having dental caries (65.9%). Two-hundred and forty-two subjects (80.9%) would not disclose their HIV status when seeing a dentist. The most cited reasons of such behavior were their personal right whether to reveal or not, and being afraid of not receiving dental treatment from the dentists or staffs (51.7 and 40.9%, respectively). It is important to note that HIV-subjects admitted to having fear of being discriminated by the dental staffs even if they trusted their dentists as having high morality. In conclusion, our HIV-subjects had good basic knowledge of oral health with regard to HIV infection, experienced common dental problems, and wished to have accesses to HIV-dental specialist services, if possible.