Diversity and compositional differences in the oral microbiome of oral squamous cell carcinoma patients and healthy controls: a scoping review.

Objectives: The human oral microbiome may play a role in the development of oral squamous cell carcinoma. The aim of this scoping review was to examine microbial diversity and differences in the composition of the oral microbiome between OSCC patients and healthy controls. Methods: A literature search (in PubMed and Embase.com) was performed on January 9, 2023. The outcome variables used from the included studies of this review were alpha- and beta diversity and oral microbiome composition profiles for each taxonomic level (phylum-, class-, order-, genus- and species level). Results: Thirteen out of 423 studies were included in this review compromising 1,677 subjects, of which 905 (54.0%) were OSCC patients and 772 (46.0%) were healthy controls. Most studies found a higher alpha diversity in the OSCC patient group and significantly different beta diversities between OSCC patient samples and healthy control samples. Studies reported more abundant Fusobacteria (on phylum level), Fusobacterium (on genus level), Fusobacterium nucleatum, Porphyromonas endodontalis and Prevotella intermedia (on species level) in OSCC patients. The healthy control group had more abundant Actinobacteria (on phylum level), Streptococcus and Veilonella (on genus level) and Veilonella parvula (on species level) according to most studies. Conclusions: Our findings show differences in oral microbiome diversity and composition in OSCC patients. Clinical implications demand continuing study. Development of internationally accepted standard procedures for oral sample collection and oral microbiota analysis is needed for more conclusive and clinically relevant comparisons in future research.

Obstructive sleep apnoea and the need for its introduction into dental curricula.

Obstructive sleep apnoea (OSA) is a major health problem which causes blood oxygen desaturation that may initiate a cascade of events via inflammatory cytokines and adrenocorticotrophic hormone that may have impact upon quality of life and lead to potential life-threatening events. Even though OSA affects an increasing number of individuals, the role of dental practitioners in recognition, screening and management has not developed accordingly. The goal of this article was to provide updated information to dental practitioners on pathophysiology, consequences and treatment options of OSA with a focused discussion on oral appliance (OA) therapy, as this topic is not routinely included in current dental curricula of many dental schools. Additionally, we present a template dental curriculum for predoctoral and/or postdoctoral students in education regarding sleep disordered breathing.

Oral complications in hematopoietic stem cell recipients: the role of inflammation.

Hematopoietic stem cell transplantation (HSCT) is widely used as a potentially curative treatment for patients with various hematological malignancies, bone marrow failure syndromes, and congenital immune deficiencies. The prevalence of oral complications in both autologous and allogeneic HSCT recipients remains high, despite advances in transplant medicine and in supportive care. Frequently encountered oral complications include mucositis, infections, oral dryness, taste changes, and graft versus host disease in allogeneic HSCT. Oral complications are associated with substantial morbidity and in some cases with increased mortality and may significantly affect quality of life, even many years after HSCT. Inflammatory processes are key in the pathobiology of most oral complications in HSCT recipients. This review article will discuss frequently encountered oral complications associated with HSCT focusing on the inflammatory pathways and inflammatory mediators involved in their pathogenesis.

Oral health conditions affect functional and social activities of terminally ill cancer patients.

PURPOSE: Oral conditions are established complications in terminally ill cancer patients. Yet despite significant morbidity,the characteristics and impact of oral conditions in these patients are poorly documented. The study objective was to characterize oral conditions in terminally ill cancer patients to determine the presence, severity, and the functional and social impact of these oral conditions. METHODS: This was an observational clinical study including terminally ill cancer patients (2.5­3-week life expectancy). Data were obtained via the Oral Problems Scale (OPS) that measures the presence of subjective xerostomia, orofacial pain, taste change, and the functional/social impact of oral conditions and a demographic questionnaire. A standardized oral examination was used to assess objective salivary hypofunction, fungal infection, mucosal erythema, and ulceration. Regression analysis and t test investigated the associations between measures. RESULTS: Of 104 participants, most were ≥50 years of age,female, and high-school educated; 45 % were African American, 43 % Caucasian, and 37 % married. Oral conditions frequencies were: salivary hypofunction (98 %), mucosal erythema (50 %), ulceration (20 %), fungal infection(36 %), and other oral problems (46 %). Xerostomia, taste change, and orofacial pain all had significant functional impact; p <.001, p =.042 and p <.001, respectively. Orofacial pain also had a significant social impact (p <.001). Patients with oral ulcerations had significantly more orofacial pain with a social impact than patients without ulcers (p =.003). Erythema was significantly associated with fungal infection and with mucosal ulceration (p <.001). CONCLUSIONS: Oral conditions significantly affect functional and social activities in terminally ill cancer patients. Identification and management of oral conditions in these patients should therefore be an important clinical consideration.

Efficacy of topical benzydamine hydrochloride gel on oral mucosal ulcers: an in vivo animal study.

The aim of this study was to investigate the effect of benzydamine hydrochloride bioadhesive gel on healing of oral mucosal ulceration in an animal model. For in vivo determination of the effects of the bioadhesive gel, 36 rabbits were separated into three groups: the first group was treated with the gel formulation without active agent, the second group with the gel formulation containing benzydamine, and the third group received no treatment. Clinical healing was established by measuring the area of the ulcer in each test group on days 3, 6, 9 and 12. Histological healing was determined on the same days. Benzydamine containing gel applications resulted in a decrease in the ulcer area in 12 days (p=0.000). Histological evaluation showed that the benzydamine group had a higher mean histological score than the base and the control groups during the whole test period, and the difference between the benzydamine group and the control group was significant (p=0.04). The bioadhesive gel formulation of benzydamine hydrochloride showed a statistically significant increased rate of mucosal repair in this experimental standard mucosal wound animal study. It is a candidate for the topical treatment of oral mucosal ulcerative lesions.

Oral complications of targeted cancer therapies: a narrative literature review.

The aim of the present study was to investigate the available literature regarding the oral side effects or adverse events associated with targeted cancer therapy. Common oral toxicities include the terms mucositis, stomatitis, dysphagia, xerostomia, pharyngitis, and taste alterations. Aims of treatment included molecules and pathways involved in carcinogenesis reported in the literature were EGFRI, VEGF, mTOR, mAbs, TKIs, and multi-kinase inhibitors. Common targeted therapies used in clinical practice or under-investigation included cetuximab, panitumumab, erlotinib, sorafenib, sunitinib malate, imatinib mesylate, bevacizumab, trastuzumab, lapatinib, and mTORs. One hundred and forty-three articles were considered relevant and included in this review. The majority of studies did not specifically address oral toxicities or include an oral clinical exam, which may lead to underreported and under-investigated oral toxicities. Further investigation is necessary to determine if the initial impression that targeted therapy produces milder oral toxicities than conventional cancer treatment is accurate.

The utility of toluidine blue staining and brush cytology as adjuncts in clinical examination of suspicious oral mucosal lesions.

The objective of this study was to investigate the utility of toluidine blue and brush cytology in patients with clinically detected oral mucosal lesions. Clinical examination of 35 patients was completed before toluidine blue application, oral brush cytology and scalpel biopsy. Lesions were photographed before and after stain application; followed by brush cytology. All findings were compared with histopathologic results. Severe dysplasia and carcinoma-in-situ were determined as 'positive'; no dysplasia and mild to moderate dysplasia were defined as 'negative'. The sensitivity, specificity, positive and negative predictive values of clinical examination and toluidine blue were the same: 0.923, 0.433, 0.414, and 0.929, respectively. Those of brush cytology were 0.923, 0.517, 0.462, and 0.938. The concordance of all methods was 30% for benign and 61% for malignant lesions. Adjuncts identified 92% of carcinoma-in-situ and squamous cell carcinoma as confirmed by histopathology, in contrast to clinical findings alone in which 62% of these lesions were identified (p=0.046). In conclusion, adjunct diagnostic methods decreased the level of uncertainty for the diagnosis of oral malignancies and lichenoid dysplasias when applied as adjuncts to clinical examination.

Analysis of oral lesion biopsies identified and evaluated by visual examination, chemiluminescence and toluidine blue.

Conventional visual examination and palpation remains the gold-standard for the identification of oral mucosal lesions. The purpose of this study was to investigate the adjunctive value of a chemiluminescent light source (ViziLite, Zila Pharmaceuticals, Phoenix, Arizona) and application of pharmaceutical grade toluidine blue (TBlue(630), Zila Pharmaceuticals, Phoenix, Arizona) to further assess lesions identified during the conventional oral soft tissue examination. Lesions deemed clinically suspicious by visual examination under incandescent light were further assessed under chemiluminescence and then application of toluidine blue stain. Differences between the conventional visual examination and chemiluminescent examination were noted on four characteristics which may aid in lesion identification. Tissue retention of toluidine blue stain was documented. Each suspicious lesion was biopsied and diagnosed based upon routine histopathology. Both adjunctive exams were evaluated by comparing the histologic diagnosis. The additive value of toluidine blue stain retention was assessed in lesions diagnosed as "serious pathology" defined as severe dysplasia, carcinoma in situ and squamous cell carcinoma. Ninety-seven clinically suspicious lesions in 84 patients were identified. The chemiluminescent exam improved the brightness and/or sharpness of margin in 61.8% of identified lesions. Biopsied lesions with toluidine blue stain retention reduced the false positive rate by 55.26% while maintaining a 100% negative predictive value (NPV). Chemiluminescence was shown to increase the brightness and margins of mucosal lesions in a majority of cases and therefore may assist in identification of mucosal lesions not considered under traditional visual examination. Toluidine blue stain retention was associated with a large reduction in biopsies showing benign histology (false positive biopsy results), while maintaining a 100% NPV for the presence of severe dysplasia or cancer. Practitioners may consider use of these adjuncts in practice, however the results presented are based upon experienced providers in referral centers for mucosal disease or cancer centers and therefore positive findings may be an indication for referral to experienced providers.

Orofacial pain in cancer: part II--clinical perspectives and management.

Cancer-associated pain is extremely common and is associated with significant physical and psychological suffering. Unfortunately, pain associated with cancer or its treatment is frequently under-treated, probably due to several factors, including phobia of opioids, under-reporting by patients, and under-diagnosis by healthcare workers. The most common etiology of cancer pain is local tumor invasion (primary or metastatic), involving inflammatory and neuropathic mechanisms; these have been reviewed in Part I. As malignant disease advances, pain usually becomes more frequent and more intense. Additional expressions of orofacial cancer pain include distant tumor effects, involving paraneoplastic mechanisms. Pain secondary to cancer therapy varies with the treatment modalities used: Chemo-radiotherapy protocols are typically associated with painful mucositis and neurotoxicity. Surgical therapies often result in nerve and tissue damage, leading, in the long term, to myofascial and neuropathic pain syndromes. In the present article, we review the clinical presentation of cancer-associated orofacial pain at various stages: initial diagnosis, during therapy (chemo-, radiotherapy, surgery), and in the post-therapy period. As a presenting symptom of orofacial cancer, pain is often of low intensity and diagnostically unreliable. Diagnosis, treatment, and prevention of pain in cancer require knowledge of the presenting characteristics, factors, and mechanisms involved.

Clinical evaluation of chemiluminescent lighting: an adjunct for oral mucosal examinations.

OBJECTIVE: The purpose of this study was to describe the utility of oral chemiluminescent lighting (FDA-cleared ViziLite) as an adjunct to standard visual examination (SVE) to enhance visualization of mucosal lesions, particularly those "clinically suspicious" for oral pre-cancer or cancer. Subjects were considered at risk for oral cancer or pre-cancer if they have no a priori knowledge of the presence or absence of an oral lesion at the time of examination. METHODOLOGY: Five-hundred and one consecutive consenting subjects, over 40 years of age and with a positive tobacco history, received a standard visual examination with conventional incandescent lighting, followed by chemiluminescent lighting. All lesions were recorded, and for lesions detected by both screening modalities, comparisons were made of the subjective parameters of lesion brightness, sharpness, surface texture, and relative size. RESULTS: A total of 410 epithelial lesions were detected in 270 subjects by standard visual examination, of which 127 were clinically "suspicious" for oral cancer and pre-cancer. Ninety-eight lesions were also visualized by chemiluminescent lighting as "aceto-white" (CL+), in addition to six lesions not previously seen by standard visual examination. Seventy-seven of the CL+ lesions (78.5%) were clinically suspicious; all "suspicious" lesions with an ulcerative component and ulcerated lesions consistent with trauma were CL+. Leukoplakias were significantly more likely to be CL+ than erythroplakias (p < 0.01). Overall, those lesions illuminated by chemiluminescent lighting appeared brighter, sharper, and smaller compared to incandescent illumination. CONCLUSION: The results of this study suggest that oral chemiluminescent lighting, when used as a screening adjunct following the standard visual oral examination, provides additional visual information. Leukoplakias may be more readily visualized by chemiluminescence. Studies are underway to explore the clinical significance and predictive value of oral chemiluminescent lighting.

Permanent vision loss in one eye following administration of local anesthesia for a dental extraction.

Prilocaine Plain, an amide local anesthetic (LA), is somewhat less potent than lidocaine and considerably less toxic after injection into peripheral tissues. Clinically, it produces less vasodilation and is similar to other amide LA in relative freedom from allergic reactions. It is reliably used in a plain solution for cardiac patients receiving short procedures. In this report a patient with a known diagnosis of bacterial endocarditis suffered permanent visual loss in the left eye immediately following dental extraction surgery prior to mitral valve surgery. The clinical implications indicate that the delivery of LA must be done with aspiration before and during the injection. This will possibly prevent intravascular injection, which can lead to fluid emboli occluding the ophthalmic artery with the devastating result of vision loss.

The relationship between mucosal cyclooxygenase-2 (COX-2) expression and experimental radiation-induced mucositis.

Although cycloooxygenase-2 (COX-2) is upregulated by factors associated with oral mucositis, its role in the pathogenesis of mucositis has not been studied. We investigated the kinetics of mucosal COX-2 expression following radiation exposure, and assessed its relationship to the development of oral mucositis in an established animal model using immunohistochemical endpoints. While little or no COX-2 expression was observed in unirradiated mucosa or in tissue taken 2 days after radiation, COX-2 expression was dramatic on days 10 and 16, especially in submucosal fibroblasts and endothelium. The kinetics of COX-2 expression paralleled mucositis severity. A burst of angiogenic activity was seen on day 21 following peak COX-2 expression. The kinetics of COX-2 expression relative to mucositis progression suggests that COX-2 is not a primary driver of radiation injury, but instead plays an amplifying role.

Quality of life, taste, olfactory and oral function following high-dose chemotherapy and allogeneic hematopoietic cell transplantation.

Multiple oral complaints develop following high-dose chemo/radiotherapy and hematopoietic cell transplantation (HCT) which can influence quality of life. The purpose of this investigation was to assess quality of life, oral function, taste and smell in a cohort of patients following HCT. A general quality of life survey (the European Organization for Research and Treatment of Cancer (EORTC)) Quality of Life (QOL) questionnaire (QLQ-C30), with an added oral symptom and function scale and assessment of taste and smell was administered to a consecutive series of patients at day 90-100 post HCT. General QOL was impacted by fatigue, affecting physical, social emotional and cognitive function. While oral function scales appeared to be little affected at day 90-100 post HCT, abnormalities of taste were reported. Reports of changes in taste and smell appeared to parallel each other and changes remained at the time of the survey post-HCT. Change in taste appeared to be closely associated with dry mouth. Patients appeared to have difficulty in differentiating sour and bitter, which had been more affected than salt and sweet taste. Females appeared to report greater changes in taste than males. Increased smell sensitivity and taste change resulted in changes in food preparation in some cases, as did reported increase in sensitivity to sour and bitter taste. Acute complications are well known to affect QOL during the early period following HCT, but little assessment of long-term changes in oral QOL and taste has been conducted following transplant. The EORTC QLQ C-30 questionnaire with the oral addendum provides a measure of the quality of life and oral function, and may provide useful outcome measures for assessment of oral care prevention and management in HCT patients.

The use of bone scintigraphy in temporomandibular joint disorders.

INTRODUCTION: The use of bone scintigraphy (bone scan) in the diagnosis of temporomandibular joint (TMJ) disease has been infrequent, as compared with traditional radiographic techniques. Bone scans have the potential to detect active bone remodeling whereas corresponding radiographs may be normal or document past structural change in the joint. Traditional radiographic findings and relevant clinical signs and symptoms correlated with bone scans may aid in the diagnosis of TMJ disease and possibly affect treatment and prognosis of individual cases. The use of bone scans as an additional tool in diagnosing TMJ disease was assessed in this series of patients. METHODS: Thirty consecutive subjects with TMJ tenderness were selected for bone scintigraphy using technetium diphosphonate 99 mTc and single photon emission computerized tomography. These subjects received bone scans as well as other selected imaging modalities for diagnostic purposes. RESULTS AND DISCUSSION: The findings on bone scan were evaluated and a change in preliminary clinical diagnosis or treatment was made in 60% of cases because of the findings on bone scintigraphy. Bone scintigraphy may be valuable to assess progress of TMJ inflammation or remodeling, and may affect diagnosis and treatment of patients with TMJ tenderness.

Comparison of HPV infection, p53 mutation and allelic losses in post-transplant and non-posttransplant oral squamous cell carcinomas.

BACKGROUND: Oral squamous cell carcinoma (SCC) is increasingly found in transplant recipients, although little is known of the natural history of the disease or the mechanism underlying this increase. METHODS: In this article we describe the history of development of 5 oral post-transplant SCCs (PSCCs) and compare their genetic profiles to 34 non-posttransplant SCCs (NPSCCs). RESULTS: Of the five patients with PSCCs, 3 had bone marrow transplants and two, kidney. All three PSCCs from bone marrow recipients were preceded locally by graft-vs.-host disease (GVHD). Two of the GVHD were biopsied and demonstrated dysplasia. Similar frequencies of loss of heterozygosity (LOH) occurred in PSCCs and NPSCCs at 3p, 9p, 17p and 8p, with lower frequencies in PSCCs at 4q (39% vs. 0%), 11q (53% vs. 20%) and 13q (45% vs. 20%), although the latter were not significantly different. Only 1 PSCC had a p53 mutation, compared to historical values of 40-60% for NPSCC. Interestingly, human papillomavirus (HPV) DNA was detected in 3 (60%) PSCCs, in comparison to only 4 (12%) of the 34 NPSCCs (P = 0.0346). CONCLUSIONS: Dysplasia in oral GVHD may be a strong indicator of cancer risk and should not be regarded as reactive changes to lichenoid mucosites. The low level of p53 mutation and increased HPV infection support the involvement of HPV in the development of PSCC, while the similarity in LOH patterns suggests that other aspects of carcinogenesis may be comparable in these two types of SCCs.

Characteristics of oral and paraoral malignant lymphoma: a population-based review of 361 cases.

BACKGROUND: Lymphoma is the second most common neoplasm of the head and neck; almost 50% of all lymphomas occur in this region. Waldeyer's ring is the most common site of lymphomas involving the oral region. The purpose of this study was to review the characteristics of a large series of malignant lymphoma of the oral region. METHODS: Three hundred sixty-one consecutive cases of malignant lymphoma of the oral region were identified in the Tumor Registry between 1969 and 1998. RESULTS: The 361 cases (200 males and 161 females) of malignant lymphoma of the oral region accounted for 3.5% of all oral malignancies. The mean age was 62.5 years and the most prevalent site of involvement was the tonsil (32.7%), followed by the parotid gland (16.1%). Sixty-five percent of the lesions were diagnosed as large-cell (38%) or small-cell (27%) lymphoma. One quarter of the patients died of the disease in a mean of 2.78 years after diagnosis. Of a total 26 patients who died from other causes, 12 died because of other cancers, including 7 (27%) with leukemia and 5 (19%) with oral carcinoma. The prognosis is based, at least partially, on the histologic grading (low, intermediate, or high) and the anatomic stage of the disease. Localized low-grade lymphomas have a more favorable prognosis compared with those that are disseminated and/or have high-grade cellular changes. CONCLUSION: Lymphoma is the second most common malignant oral disease. Thorough head and neck and oral examination is necessary to identify lesions that may represent lymphoma.

Periodontal disease and periodontal management in patients with cancer.

Periodontal infection may exacerbate during cancer therapy and may result in oral pain and infection, and systemic infection, which may cause morbidity and can lead to mortality in neutropenic cancer patients. Periodontal disease in head and neck cancer patients treated with radiation therapy may lead to acute and chronic complications. The literature was reviewed by a search of Medline of the National Library of Medicine. The search was conducted to identify publications assessing periodontal disease in cancer patients. In addition, a review of papers referenced in the retrieved papers was conducted to identify additional publications for review. Periodontal disease should be assessed and managed prior to medical treatment of cancer for those with oropharyngeal cancer, and for patients in whom neutropenia may develop during treatment. Pretreatment assessment and management, and maintenance of oral hygiene have been shown to be effective in preventing oral and systemic complications during treatment. A complete oral and periodontal examination is appropriate for all patients planned to receive head and neck radiation therapy and those to be treated with medical protocols that are anticipated to result in neutropenia. Oral and periodontal care must continue following cancer therapy, and requires that the health care provider have an understanding of the malignant disease, oral manifestations of the disease, medical management of the disease, and of the oral complications that may develop.

Oral topical doxepin rinse: analgesic effect in patients with oral mucosal pain due to cancer or cancer therapy.

Oral mucositis is a treatment limiting toxicity of cancer therapy. The purpose of this study was to assess the impact of doxepin oral rinse in the management of oral mucosal pain in cancer patients. Forty-one cancer patients with oral mucosal pain were provided a solution of doxepin (0.5%) for oral rinsing. Oral pain was assessed prior to rinsing, and following rinsing for 4 h using a visual analogue scale (VAS). Adverse effects were recorded. Doxepin rinse resulted in a reduction of pain intensity of more than 50%, with pain relief extending for more than 3 h with pain not returning to baseline 4 h after rinsing. The rinse was tolerated by patients with mucosal damage, and had acceptable taste, and infrequent mucosal stinging with use. Some patients reported sedation after use, likely due to systemic absorption. The results of this single dose trial suggest that topical doxepin rinse has significant ability to provide clinically significant pain relief in patients with mucosal damage with an extended duration of effect.

Benzydamine HCl for prophylaxis of radiation-induced oral mucositis: results from a multicenter, randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Benzydamine was evaluated in patients with head and neck carcinoma for treatment of radiation-induced oral mucositis, a frequent complication of radiation therapy (RT) for which there is no predictable therapy or preventive treatment currently available. METHODS: The safety and efficacy of 0.15% benzydamine oral rinse in preventing or decreasing erythema, ulceration, and pain associated with oral mucositis during RT were evaluated in a randomized, placebo-controlled trial conducted in patients with head and neck carcinoma. Subjects were to rinse with 15 mL for 2 minutes, 4-8 times daily before and during RT, and for 2 weeks after completion of RT; study evaluations were conducted before RT and routinely thereafter up to 3 weeks after RT. RESULTS: During conventional RT, regimens up to cumulative doses of 5000 centigrays (cGy) benzydamine (n = 69) significantly (P = 0.006) reduced erythema and ulceration by approximately 30% compared with the placebo (n = 76); greater than 33% of benzydamine subjects remained ulcer free compared with 18% of placebo subjects (P = 0.037), and benzydamine significantly delayed the use of systemic analgesics compared with placebo (P < 0.05). Benzydamine was not effective in subjects (n = 20) receiving accelerated RT doses (> or = 220 cGy/day). The incidence of adverse events between treatment groups was comparable without significant differences. Early discontinuation because of adverse events occurred in 6% of benzydamine subjects and 5% of placebo subjects, and there was 1 death (related to the primary diagnosis) in a placebo subject. CONCLUSIONS: Benzydamine oral rinse was effective, safe, and well tolerated for prophylactic treatment of radiation-induced oral mucositis.