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.

[A PhD completed. Long-term effects of childhood cancer therapy on oral health]. / Serie: Hora est. Langetermijneffecten van de behandeling van kinderkanker op de mondgezondheid.

In recent years, the five-year survival rate for childhood cancer has increased to about 80%. However, childhood cancer therapy can have serious long-term adverse effects on general health later in life. Of survivors, 75% experience 1 or more late effects. This PhD research aimed to gain more insight into the long-term effects on oral health of childhood cancer therapy, 15 years or more after diagnosis. This study, which is part of the Dutch Childhood Cancer Survivor Study Late Effects 2 (DCCSS LATER 2 Study), showed that oral complications such as dental developmental disorders and hyposalivation occur frequently. Most important risk factors were head and neck radiotherapy of the salivary glands, (alkylating) cytostatic agents, and age at the time of the cancer diagnosis. Dentists should be aware of childhood cancer in the medical history of their patient and of the type of therapy received. Regular dental visits are an essential part of long-term follow-up care of childhood cancer survivors.

Hemodynamics of the oral mucosa during cooling: A crossover clinical trial.

Objective: Oral cryotherapy is used to prevent the onset of oral mucositis, a common and debilitating adverse effect following cancer chemotherapy. A protective mechanism associated with oral cooling is thought to be mediated through reduced tissue microcirculation. The aim of the present study was to examine the underlying mechanism associated with oral mucosal cooling by measuring oral microcirculation and tissue oxygen saturation after cooling with ice chips (IC) and an intraoral cooling device (ICD). Study design: In a single-center randomized crossover study, 10 healthy volunteers were assigned (1:1) randomly to the order in which the two intraoral cooling procedures (IC/ICD) were to be commenced. On day 1, half of the study participants started with IC and then crossed over to intraoral cooling with the ICD on day 2, while the other half of the participants undertook the same two procedures in the reverse order. Total and functional capillary density (T/FCD) and tissue oxygen saturation (StO2) measurements were obtained at baseline and 30 min following oral cooling. Results: Following 30 min of oral cooling, a statistically significant difference was found for FCD between IC and ICD (percentage points; +2 vs. -13; p < 0.05). A statistically significant decrease in StO2 was observed with both IC and ICD (%; 13 vs. 10) after 30 min of cooling as compared to baseline (p < 0.05). As for the participants' preference the ICD was preferred over IC by 9 out of 10 participants (p = 0.021). Conclusions: Both microcirculation parameters and tissue oxygen saturation are altered in conjunction with oral cooling, indicating their potential mechanistic contribution towards cryoprevention of oral mucositis.

The salivary proteome in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients: a labelled and label-free proteomics approach.

BACKGROUND: Oral mucositis is a frequently seen complication in the first weeks after hematopoietic stem cell transplantation recipients which can severely affects patients quality of life. In this study, a labelled and label-free proteomics approach were used to identify differences between the salivary proteomes of autologous hematopoietic stem cell transplantation (ASCT) recipients developing ulcerative oral mucositis (ULC-OM; WHO score ≥ 2) or not (NON-OM). METHODS: In the TMT-labelled analysis we pooled saliva samples from 5 ULC-OM patients at each of 5 timepoints: baseline, 1, 2, 3 weeks and 3 months after ASCT and compared these with pooled samples from 5 NON-OM patients. For the label-free analysis we analyzed saliva samples from 9 ULC-OM and 10 NON-OM patients at 6 different timepoints (including 12 months after ASCT) with Data-Independent Acquisition (DIA). As spectral library, all samples were grouped (ULC-OM vs NON-OM) and analyzed with Data Dependent Analysis (DDA). PCA plots and a volcano plot were generated in RStudio and differently regulated proteins were analyzed using GO analysis with g:Profiler. RESULTS: A different clustering of ULC-OM pools was found at baseline, weeks 2 and 3 after ASCT with TMT-labelled analysis. Using label-free analysis, week 1-3 samples clustered distinctly from the other timepoints. Unique and up-regulated proteins in the NON-OM group (DDA analysis) were involved in immune system-related processes, while those proteins in the ULC-OM group were intracellular proteins indicating cell lysis. CONCLUSIONS: The salivary proteome in ASCT recipients has a tissue protective or tissue-damage signature, that corresponded with the absence or presence of ulcerative oral mucositis, respectively. TRIAL REGISTRATION: The study is registered in the national trial register (NTR5760; automatically added to the International Clinical Trial Registry Platform).

[Oral chronic graft versus host disease, what is it and how is it treated?] / Orale chronische graft-versus-hostziekte, wat is het en hoe wordt het behandeld?

Allogeneic stem cell transplantation can cause chronic graft versus host disease (cGVHD). A number of patients manifest cGVHD in and around the mouth. It can present itself as clinically as mucosal lesions and/or salivary gland dysfunction and/or sclerotic changes. Cheeks and tongue are most commonly affected, but the palate, gingiva and lips can also be impacted. Oral cGVHD is associated with mucosal sensitivity, pain, (severe) oral dryness, altered taste, restricted mouth opening and difficulty swallowing, all of which may contribute to a significant decrease of the patient's quality of life. Patients also run an increased risk of developing squamous cell carcinoma of the oral mucosa. The diagnosis of cGVHD is almost always based on the patient's medical history and clinical picture. Treatment of symptoms is based on the patient's problem(s). Dental professionals can provide patients with supportive preventive care aimed at reducing symptoms and preventing further deterioration of oral health.

Significant salivary changes in relation to oral mucositis following autologous hematopoietic stem cell transplantation.

The aim of this multicentre, longitudinal study was to determine salivary changes in relation to oral mucositis (OM) in multiple myeloma patients following high-dose melphalan and autologous hematopoietic stem cell transplantation (ASCT). Unstimulated and stimulated whole-mouth saliva samples (UWS and SWS) were collected before ASCT, 1×/wk during the hospitalisation phase, and 3 and 12 months post-ASCT. During the hospitalisation period OM was scored 3×/wk (WHO system). Flow rate, pH, total protein concentration (Nanodrop), albumin, lactoferrin, neutrophil defensin-1 (HNP1), total IgA and S100A8/A9 (ELISA) were determined. Mixed models were used to evaluate differences between ulcerative (u)OM (≥2 WHO, n = 20) and non-uOM (n = 31) groups. Until 18 days after ASCT, flow rate, pH, total IgA and HNP1 levels decreased in UWS and/or SWS, while log lactoferrin levels were significantly increased (UWS: p = 0.016 95% CI [0.36, 3.58], SWS: p < 0.001 95% CI [1.14, 3.29]). Twelve months post-ASCT, salivary protein levels were similar to baseline except for log total IgA, which was higher (UWS: p < 0.001 95% CI [0.49, 1.29], SWS: p < 0.001 95% CI [0.72, 1.45]). No differences between uOM and non-uOM groups were observed. Changes in salivary proteins indicated an inflammatory reaction in salivary glands coinciding with mucosal and systemic reactions in response to high-dose melphalan.

[Medicaments and oral healthcare. Adverse effects of medications on the oral mucosa]. / Serie: Medicamenten en mondzorg. Bijwerkingen van medicatie op de orale mucosa.

Many medications prescribed in the Netherlands have adverse effects on the oral mucosa. Adverse events often described are stomatitis, white lesions, abnormal pigmentation and sensibility disorders. Stomatitis is frequently observed in patients using medications for the treatment of malignancies or auto-immune diseases. Important causative classes of medicines are alkylating agents, anthracyclines, monoclonal antibodies, protein kinase inhibitors, purine derivatives, pyrimidine antagonists, taxanes and vinca alkaloids. White oral lesions often concern candidiasis and are frequently seen in patients using certain immunosuppressants and antibiotics. Abnormal pigmentation is frequently seen in patients using hydroxycarbamide, an antineoplastic agent. Sensibility disorders of the oral mucosa are described in several classes of medications, including protein kinase inhibitors. It is very important oral healthcare professionals can recognise possible adverse effects of medications on the oral mucosa. When it is probable an anomaly of the oral mucosa is caused by medication, the oral healthcare professional should contact the prescribing physician to discuss the possibility of adjusting or discontinuing the medication.

[Oral graft-versus-host-disease: implications for dental professionals]. / Orale graft-versus-hostziekte: implicaties voor mondzorgverleners.

Graft-versus-host disease (GVHD) is a serious complication after allogeneic hematopoietic stem cell transpl antation, which frequently affects the mouth. GVHD is the result of an immunological attack of donor-derived cells against the tissue of patients. Chronic oral GVHD can affect the mucosa and/or damage salivary glands and can cause sclerotic changes to the head and neck area. Patients can experience painful oral and gingival mucosa, dry mouth, taste changes and limited mouth opening. Due to painful mucosa and salivary glands, and limited mouth opening, performing oral hygiene and dental interventions can be difficult. Immunosuppression in combination with altered salivary production increases the risk of secondary infectious complications, such as dental caries and candida infections. Dental professionals can play an important role in the prevention of oral complications.

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.

Viral loads and antiviral resistance of herpesviruses and oral ulcerations in hematopoietic stem cell transplant recipients.

Ulcerative oral mucositis and infection are frequent complications in hematopoietic stem cell transplant (HSCT) recipients. The aim of this study was to investigate the relationship between oral ulcerations and HSV-1, EBV and CMV excretion and the presence of aciclovir-resistant HSV-1 strains in HSCT recipients. This prospective observational study included 49 adult patients who underwent allogeneic HSCT. In total, 26 patients received myeloablative and 23 received non-myeloablative conditioning. Ulcerations on non-keratinized and keratinized oral mucosa were scored and oral rinsing samples were taken twice weekly. Viral loads were determined by real-time PCR. Samples from patients remaining HSV-1 positive despite antiviral treatment were studied for resistance to antivirals. Having an HSV-1 or EBV DNA-positive sample was a significant predictor for ulceration of keratinized mucosa. HSV-1 was a significant predictor for ulcerations on non-keratinized mucosa as well. Persistent HSV-1 infection occurred in 12 of 28 patients treated with antiviral medication and aciclovir-resistant HSV-1 was found in 5 persistent infections. In conclusion, HSV-1 is a predictor of ulcerations on non-keratinized as well as keratinized oral mucosa following HSCT. The role of EBV deserves further study. Persistent HSV-1 replication despite antiviral treatment is common and is due to resistance in 18% of treated patients.

Longitudinal assessment of hematopoietic stem cell transplantation and hyposalivation.

Hyposalivation is a common adverse effect of anti-neoplastic therapy of head and neck cancer, causing impaired quality of life and predisposition to oral infections. However, data on the effects of hematopoietic stem cell transplantation (HSCT) on salivary secretion are scarce. The present study determined stimulated whole-saliva flow rates in HSCT recipients in comparison with a healthy control group. Stimulated whole-saliva flow rates of 228 allogeneic HSCT recipients (134 males, 94 females; mean age, 43 yrs) were examined pre-HSCT and 6, 12, and 24 months post-HSCT. Healthy individuals (n = 144; 69 males, 75 females; mean age, 46 yrs) served as the control group. Stimulated saliva flow rates (mL/min) were measured and analyzed statistically, stratifying for hematological diagnoses and conditioning therapy. Hyposalivation (≤ 0.7 mL/min) was found in 40% (p < 0.00001), 53% (p < 0.00001), 31% (p < 0.01), and 26% (n.s.) of the recipients pre-HSCT, and 6, 12, and 24 months post-HSCT, respectively, whereas 16% of the control individuals had hyposalivation. Severe hyposalivation (≤ 0.3 mL/min) was found in 11%, 18%, 4%, and 4% of the recipients pre-HSCT, and 6, 12, and 24 months post-HSCT, respectively. Additionally, conditioning regimen and sex had an impact on saliva flow. In conclusion, hyposalivation was observed to be a common but generally reversible complication among HSCT recipients.

[Tooth development disturbances following haematopoietic stem cell transplantation]. / Langetermijneffecten op de gebitsontwikkeling na stamceltransplantatie.

Forty children treated with allogenic haematopoietic stem cell transplantation for haematological malignancies, were examined at least 2 years after transplantation. The researchers collected information concerning subjective oral symptoms, the results of a panoramic radiograph and the findings of an oral examination. Nearly all children had tooth development disturbances, including missing teeth, shortened roots, and arrested root development. The study group showed a significantly higher prevalence of missing teeth than the standard values for first and second premolars in both maxilla and mandible, as well as for second molars in the mandible. Children younger than 3 years of age at the start of the treatment missed significantly more teeth than older children. The mean root-crown length ratios of several tooth types were lower when compared with a control group of healthy Finnish children. The mean dental age was higher than the mean chronological age due to early final apical root formation.

Xerostomia and chronic oral complications among patients treated with haematopoietic stem cell transplantation.

OBJECTIVE: To assess the severity of xerostomia (subjective dry mouth) in haematopoietic stem cell transplantation (HSCT) patients and to investigate the association of xerostomia with other chronic oral complications. DESIGN: Cross-sectional study.Study participants and methods Participants were 48 patients with a history of HSCT recruited among members of the Dutch Stem Cell Transplantation Contact Group, and a comparison group of 41 age- and sex-matched individuals. Data were collected using the Xerostomia Inventory (XI score) and a seven-item oral health questionnaire. RESULTS: HSCT patients had a higher XI score than the comparison group, and a greater severity of several oral complaints: painful oral mucosa, altered taste, limited opening of the mouth and problems with tooth brushing. HSCT patients did not report greater pain during cold stimulation of teeth, chipped and cracked teeth or bleeding gums. In HSCT patients, the XI score correlated significantly with the severity of oral mucosal pain, altered taste, limited opening of the mouth, painful teeth following cold stimuli, chipped or cracked teeth, problems with tooth brushing and bleeding gums. In the comparison group, no correlations were observed between XI score and these oral problems. CONCLUSION: HSCT patients have more severe xerostomia, which is associated with other oral complaints. Dental professionals should monitor these patients post-transplant for oral complications. Symptoms of dry mouth should be relieved and secondary complications should be prevented.

[Haematopoietic stem cell transplantation and oral complications]. / Hematopoëtische stamceltransplantaties en orale problemen.

New haematopoietic stem cell transplantation procedures make the treatment available to patients who previously did not qualify, such as the elderly. In addition, the spectrum of oral complications associated with haematopoietic stem cell transplantation has altered as a result of the recent developments. This article is a review of the main principles of haematopoietic stem cell transplantation and provides information on oral complications which may develop, such as mucositis, infections, bleeding, graft-versus-host disease, xerostomia, hyposalivation, altered taste, secondary tumors, osteoporosis, osteonecrosis and growing and developing disturbancies. Finally, the role of dental care providers in cases of haematopoietic stem cell transplantation is addressed.

Long-term adverse effects of hematopoietic stem cell transplantation on dental development in children.

PURPOSE: The purpose of this study was to assess late effects of cytotoxic therapy with hematopoietic stem cell transplantation (HCT) on dental development in survivors of childhood cancer. MATERIALS AND METHODS: Forty children who underwent allogeneic HCT for a variety of hematological malignancies were evaluated at a minimum of 2 years after transplantation. We obtained information on oral symptoms, exposed panoramic radiographs (PRG), and performed an oral examination. PRGs were scored for agenesis and root and/or crown abnormalities. The root-crown ratio was calculated, and dental age was assessed using Demirjian' s method. MAIN RESULTS: The studied group showed a significantly higher prevalence of tooth agenesis compared to normative data for first and second premolars in both the maxilla and mandible, as well as the second molars in the mandible (all p values <0.001). Children who were <3 years old at the time of cancer treatment had significantly more missing teeth than older children, F(2,37) = 7.58, p < 0.002. Root-crown ratios were lower in the study sample than those from normative data. In addition, the mean dental age was higher (as a result of earlier apical root closure) than the mean chronological age, t(28) = 2.47, p < 0.020. CONCLUSIONS: Nearly all children examined had dental development disturbances, including agenesis, short roots, and arrested root development. An oral/dental evaluation and preventative oral supportive care regimens should be part of programs monitoring late effects in long-term survivors of childhood cancer.

Oral mucositis in patients treated with chemotherapy for solid tumors: a retrospective analysis of 150 cases.

The incidence and the severity of chemotherapy-associated oral mucositis were determined in a retrospective analysis of 150 patients with various solid tumors. In addition, possible risk factors for the development of mucositis were identified. Patients were treated with chemotherapeutic regimens appropriate to tumor type and disease stage on an in- or outpatient basis. Mucositis was scored using the World Health Organization (WHO) criteria. Eighty-seven episodes of mucositis occurred in 47 (31%) patients. Twenty-six patients each experienced only one episode, whereas 21 patients had up to eight episodes of mucositis. The 1,281 chemotherapy cycles that have been analyzed included 87 cycles in which mucositis was observed. In 16 patients (11%) only slight oral mucosal changes were recorded (maximum WHO score 1), while 25 patients (17%) experienced mild to moderate mucositis (maximum WHO score 2), and in 6 patients (4%) mucositis was moderate to severe (maximum WHO score 3). No grade 4 mucositis developed. In 24 of the 47 patients with mucositis (51%) clinical features of acute pseudomembranous candidiasis were present. Leukopenia, leukopenic fever, and use of corticosteroids and central venous catheters were associated with the chemotherapy cycles with mucositis. Multivariate analysis identified the administration of paclitaxel, doxorubicin, or etoposide as independent risk factor (adjusted rate ratios 8.06, 7.35, and 6.70, respectively), whereas low body mass was associated with a slightly increased risk (adjusted rate ratio 0.92) for the development of mucositis. In conclusion, almost one-third of patients receiving chemotherapy for solid tumors experienced one or more episodes of mild to more severe oral mucositis, indicating that this is a frequent complication in such patients.

Current practices for management of oral mucositis in cancer patients.

Many anticancer therapies induce oral mucositis, diminishing the patient's quality of life. Especially in neutropenic patients, it can lead to life-threatening systemic infection. Moreover, it can become a limiting factor in intensive treatment schedules. Many interventions are aimed at reducing trauma and the risk of secondary infection. The institution of good oral hygiene seems to play a crucial part and can be achieved manually or by means of antiseptic agents. More specific antimicrobial therapy may be indicated. In addition, local and/or systemic pain control may be required. The administration of hematological growth factors, cryoprotectants and other agents or measures that may be of help in the management of mucositis are discussed.

[The significance of endocrine factors and microorganisms in the development of gingivitis in pregnant women]. / Znachenie éndokrinnykh faktorov i mikroorganizmov v razvitii gingivita beremennykh.

40-100% of pregnant women suffer from the co-called pregnancy gingivitis. The cause of pregnancy gingivitis is possible multicausal: increased plasma female sex-hormones, alteration in dental plague and perhaps Prevotella intermedia in the subgingival plague, together with alteration of immunoresponse. Increasing levels of progesterone in the gingiva as well as estrogens due to specific receptors affect vascular permeability and exudation, provoke stasis of microcirculation, increase prostaglandine E2 formation in human gingiva. Decreased gingival keratinization and capability of cell regeneration may affect the epithelial barrier. This can perhaps explain the direct dependence between progesterone and estrogens increasing and the intensification of gingivitis clinical manifestation. The experimental gingivitis model of women during pregnancy and post-partum showed identical amounts of dental plague, but clinical manifestations were more intense during pregnancy and they had a relation with increasing P. Intermedia, no statistical significance was shown in the proportion of P. gingivalis. Increasing steroid hormones can substitute for the naphtoquinone requirement of P. intermedia. Optimal oral hygiene performed during pregnancy reduced gingival swelling, redness and bleeding tendency to levels which can be considered as physiologic for the pregnant state.

Experimental gingivitis during pregnancy and post-partum: clinical, endocrinological, and microbiological aspects.

The purpose of this study was to assess whether an intensive oral hygiene regimen practised during pregnancy results in a clinically healthy gingival state, and to assess whether experimentally-induced gingivitis differs in severity during pregnancy as compared to post-partum. In addition, levels of black-pigmented Gram negative anaerobes at subgingival and oral mucosal sites and plasma concentrations of free estrogens and prosterone were determined. These parameters were studied during a 14-day episode of experimental gingivitis induced in the 25th week of pregnancy, and again 6 months post-partum. The subjects were selected on shallow pockets < or = 4 mm and interproximal loss of attachment not exceeding 2 mm. As a result of controlled oral hygiene, the gingival condition improved both during pregnancy and post-partum. At day 0 during pregnancy, however, gingival swelling, redness, and bleeding on probing were found to be higher than post-partum. Free plasma levels of estrogens and progesterone were found to be normal throughout the study. It was hypothesized that the increase in severity of gingival symptoms during pregnancy reflect microvascular physiologic effects of increased levels of these hormones. During pregnancy, more swelling, redness and bleeding on probing developed during experimental gingivitis than post-partum, whereas the amount of plaque was similar in both phases. This suggests that as a result of dental plaque accumulation, gingival inflammation develops superimposed on pregnancy-associated physiologic alterations. Microbiological evaluation showed that the mean proportions of Prevotella intermedia in subgingival plaque increased during experimental gingivitis performed during pregnancy, whereas no increase of this micro-organism was found post-partum.

Efficient and unbiased estimation of volume and area of tissue components and cell number in gingival biopsies.

Recently, the methodology for volume and cell number estimation from sectioned tissue has undergone rapid progress. To date there are no indications in the literature that investigators in periodontal research are aware of this progress, published mainly in the disciplines of stereology and morphometry. This is unfortunate, as these developments could be profitably exploited in periodontal pathology. In this review we discuss the dangers of some currently used quantitative methods and indicate how simple unbiased methods together with an appropriate systematic sampling scheme lead to an efficient estimation of cell number and volume of tissue or tissue components.