Intermediate filaments in oral neoplasia. I. Oral cancer and epithelial dysplasia

The major value of intermediate filaments (IFs) in biological and applied research lies in their high order of cell and tissue specificity. This is particularly well illustrated in keratin (K) expression in various oral epithelia. Although the original class of IF is usually conserved in tissues after neoplastic transformation, epithelia show a tendency to shift their pattern of keratin expression in a manner which, while not predictable with precision, may sometimes be of diagnostic or prognostic significance. This review compares the keratins in normal oral epithelia, which show a mainly site-dependent expression, with those in squamous cell carcinoma. Key changes in the latter are the presence of simple epithelial keratins, K8 and K18 (occasional K7), reduced expression of differentiation-linked keratins (K1, K10, K4 and K13) and a tendency for down-regulation of primary keratins, K5 and K14. Moderate and severe dysplasias also tend to exhibit K8 and K18 with concomitant disordered expression of differentiation-linked keratins. There are reports of similar changes after neoplastic transformation in other mucosal sites and skin. Before this information can be applied diagnostically in immunocytochemical studies, the anti-keratin antibodies must be fully characterised and their interaction with the relevant tissue, both frozen and conventionally processed, should be evaluated.     

Malignant transformation in a cohort of patients with oral epithelial dysplasia

Oral epithelial dysplasia (OED) is often diagnosed in oral potentially malignant disorders (OPMD) and carries an increased risk of malignant transformation. Currently, the reported risk of malignant transformation for OED varies. Here we present the risk in a cohort of 150 patients with OED at a specialist centre. In this cohort 2.6%, 4.1%, and 29.2% cases of mild, moderate, and severe OED, respectively, progressed to oral squamous cell carcinoma at the dysplastic site, while a small number developed a malignant lesion elsewhere. Moreover, 17 patients experienced an increase in grade of dysplasia and two showed histological resolution of their lesions.     

Putative cancer stem cell marker expression in oral epithelial dysplasia and squamous cell carcinoma

Multifactorial conditions underlie progression of potentially malignant oral lesions (PMOL) to oral squamous cell carcinoma (OSCC) and there is currently need for better prediction of malignant transformation. The hypothesised existence of cancer stem cells in dysplastic oral tissues provides the potential for more informed assessment of PMOL progression. Semi‐quantitative immunohistochemical assessment of four putative cancer stem cell markers (CD24, CD44, CD271 and ALDH1) was conducted with a training cohort of 107 patient biopsies to establish clinically applicable score threshold values that were subsequently applied to a blind diagnosis in an independent validation cohort of 278 biopsies. Stain intensity scores for ALDH1, CD24 and CD44, but not CD271 were greater for OSCC than normal tissues. The intensity of ALDH1 and CD24 immunostaining correlated with increased oral epithelial disease severity, and CD24 was effective in distinguishing OSCC from non‐malignant tissues, correctly diagnosing 71% of OSCC cases in the validation cohort. Importantly, CD24 immunostaining was effective in diagnosing the presence of dysplasia, correctly discriminating 69% of dysplasia tissues from normal tissues, although no distinction between mild and severe grades of dysplasia was achieved. The results highlight CD24 immunostain intensity as an effective marker of oral dysplasia and OSCC. In conclusion, CD24 immunostain intensity scoring may serve as a helpful technique to assist with the histological recognition of dysplasia in oral biopsies, but not for distinguishing between grades of dysplasia.     

Description of persons with symptoms presumed to be caused by electricity or visual display units—oral aspects

A questionnaire containing 20 questions was sent to 127 members of the Association for Those Injured by Electricity and Visual Display Units in northern Sweden, of whom 103 (81%) answered. The questionnaire consisted of questions about age, sex, and place of work. Furthermore, the members were asked to state: 1) their general and oral symptoms; 2) whether they thought that dental amalgam and other types of dental filling materials had affected their symptoms; 3) whether they were replacing or had replaced their amalgam fillings and, if so, what effect it had had on their symptoms; 4) whether they had been medically examined; and 5) whether they were or had been sick-listed for their complaints. Of those who answered the questionnaire, 79% were women (mean age 45 yr) and 21% men (mean age 42 yr). Sixty percent worked in offices. In 82%, the symptoms had started at work. The mean duration of the symptoms was 5.2 yr. The symptoms were aggravated mostly in "electric environment in general" and in "office with computers". Skin complaints, fatigue, and eye symptoms were the most common general symptoms. Sixty-five percent mentioned that they had oral symptoms. Gustatory disturbances, burning mouth, and temporomandibular joint (TMJ) dysfunction were the most common oral symptoms. Fifty-six percent considered that dental amalgam and 24% that other dental materials affected the symptoms. Twenty-one percent were in the process of replacing the amalgam fillings; 40% had already done so. After replacement, 37% had noticed a decrease of symptoms. Most had been medically examined for their complaints, and 81% had been sick-listed. Forty-two percent had received "alternative care". Finally, a treatment protocol for the examination and treatment of patients with symptoms caused by electricity or visual display units (VDUs) is recommended.     

Evaluation of oral bacteria as risk indicators for periodontitis in older adults.

The prevalence of people and sites with attachment loss, pocket depth, Actinobacillus actinomycetemcomitans, Prevotella intermedia, and Porphyromonas gingivalis are described for a random sample of 366 black and 297 white community-dwelling adults, aged 65 or over, residing in five counties in North Carolina. In addition, relationships between sites harboring these microorganisms and loss of attachment (LA) and pocket depth (PD) are presented in a manner that considers the lack of independence of sites within each person. Pocket depths and recession were measured on all teeth by trained examiners during household visits. Immunofluorescent assays for A. actinomycetecomitans, P. intermedia, and P. gingivalis were conducted on subgingival plaque samples obtained from the mesiobuccal aspect of the four first molar teeth using paper points. The prevalences of A. actinomycetemcomitans, P. intermedia, and P. gingivalis were greater in blacks than in whites. The most striking difference was seen for P. gingivalis, which was found in 38.8% of blacks and 9.4% of whites. Similar relationships were found when the percent of sites with these organisms were assessed. Blacks with P. gingivalis or P. intermedia had a higher prevalence of sites with LA greater than or equal to 7 mm as compared to blacks not infected with P. gingivalis or P. intermedia. The same was true for whites. Similar relationships between P. gingivalis or P. intermedia and PD greater than or equal to 6 mm were found for both blacks and whites.(ABSTRACT TRUNCATED AT 250 WORDS)     

Predictive factor for photodynamic therapy effects on oral squamous cell carcinoma and oral epithelial dysplasia

Objective

The aim of this study was to investigate the correlation between the immunohistochemical expression of proliferating cell nuclear antigen (PCNA), factor VIII, and CD34 (markers of endothelial cells), and vascular endothelial growth factor (VEGF) and the recurrence of oral squamous cell carcinoma (OSCC) and oral epithelial dysplasia (OED) subjected to photodynamic therapy (PDT).

Design

Twenty-one biopsy specimens (14 cases of OSCC and 7 cases of OED) before PDT were immunohistochemically investigated in terms of their expressions of PCNA, factor VIII, CD34 and VEGF. The percentages of the total sample area that were immunopositive for factor VIII (percentage factor VIII immunopositive area: PFIA) CD34 (PCIA) and VEGF (PVIA) were calculated using computer-assisted image analysis for quantitative assessment of endothelial cells or VEGF expression in the lesions. The PCNA labelling index (LI) was evaluated as a proliferation marker.

Results

Five cases of OSCC and one case of OED recurred 4 to 30 months after PDT. We found that the average PVIA was 14.5% in the no-recurrence group and 1.7% in the recurrence group. The difference between these values was statistically significant (P = 0.0483). On the other hand, the average PCNA LI was 30.3% in the no-recurrence group and 24.3% in the recurrence group; the average PFIA was 3.7% in the no-recurrence group and 1.6% in the recurrence group; and the average PCIA was 2.0% in the no-recurrence group and 1.4% in the recurrence group. There were no significant differences between the two groups for any of these markers (P = 0.3379, P = 0.1195, P = 0.4835, respectively).

Conclusions

These results provide clinical data indicating that VEGF expression may be a useful predictive marker for the effects of PDT in OSCC and OED.     

Tobacco use and oral hygiene as risk indicators for periodontitis

OBJECTIVE: To detect the periodontal status of male smokers and betel chewers in a rural community in Sri Lanka and compare it with that of male non-tobacco users of the same community. METHODS: A cross-sectional community based study was carried out in a sample of 2277 rural adult males aged 20-60 years, adopting multistage cluster sampling technique. The present analysis was confined to 2178 subjects who were mutually exclusive smokers, betel chewers or non-tobacco users. The periodontal status was assessed by clinical measurement of levels of bacterial plaque (PLI), gingival inflammation (GI) and loss of epithelial attachment (LA). All measurements were carried out on four sites of all teeth present except third molars and the mean values for periodontal parameters were calculated. RESULTS: Bivariate analysis revealed that the overall periodontitis levels were significantly higher in betel chewers and smokers than in non-tobacco users. Multiple linear regression analysis showed that there were no significant effects of smoking and betel chewing per se on LA, independent of age, socioeconomic status (SES) and whether or not controlled for PLI. The effect of the quantified tobacco use on LA was statistically significant regardless of age, PLI or SES. However, the effect of the quantified tobacco use was considered limited when compared to that of oral hygiene. CONCLUSIONS: The findings highlighted the importance of oral hygiene in the aetiology of periodontitis while confirming the statistical significance of the quantified tobacco use on LA. Oral hygiene and the quantified tobacco use may be considered as risk indicators for periodontitis.     

Unique FISH patterns associated with cancer progression of oral dysplasia

Subgroups of patients with oral pre-malignant lesions (OPLs) are at extremely high risk for developing invasive cancer in spite of surgical excision. The objective of this study was to evaluate the utility of specific genes and their associated centromeres as markers to stratify OPLs for their cancer risk. Samples used in this study included 35 oral dysplasia with known outcome and 20 normal oral mucosa. Of the dysplasias, 20 were from an ongoing longitudinal study showing progression. The remaining 15 cases (2 of which progressed) were chosen from the population-based, provincial BC Oral Biopsy Service (OBS). Copy number alterations at EGFR, CEP7, CCND1, and CEP11 were evaluated by fluorescent in situ hybridization (FISH). There was no significant difference in demographics between progressors and non-progressors. Specific FISH profiles at these genes and their corresponding centromeres were associated with progression. High gene gain of CCND1 was associated with an 8-fold elevated risk of progression compared with those with no gain in time-to-progression analysis. Numerical alterations of EGFR and CCND1 and their centromeres might be an effective means for identifying OPLs at risk. Future studies will expand on this analysis and set the stage for application of this approach in routine clinical practice.     

Reactivity of monoclonal antibodies 17.13 and 63.12 with oral epithelial dysplasia and hyperkeratosis

Monoclonal antibodies (MAbs) 17.13 and 63.12 exhibit characteristic reactivity patterns in normal stratified squamous epithelium, as well as highly sensitive and specific altered reactivity patterns in squamous cell carcinoma. The purpose of this study was to critically evaluate the patterns of reactivity of MABs 17.13 and 63.12 in 43 biopsies of clinical oral leukoplakia or erythroleukoplakia with microscopic diagnoses of hyperkeratosis or epithelial dysplasia. Altered carcinoma-like reactivity patterns were seen in 72% of hyperkeratoses and in all cases of epithelial dysplasia, but varied in the level of epithelial strata exhibiting altered reactivity. Increased frequency of altered reactivity within the epithelial strata was associated with the presence, but not the grade of, epithelial dysplasia, as well as with the presence, intensity, and pattern of submucosal inflammation. The results of this study suggest that altered reactivity patterns of MAb 17.13 are associated with epithelial dysplasia and may be of assistance in detecting precancerous changes in hyperkeratoses before morphologically identifiable epithelial dysplasia. The association of submucosal inflammation with altered MAbs 17.13 and 63.12 reactivity may indicate either a decrease in specificity of these antibodies for precancerous change or an increased significance of inflammation in precancerous lesions.     

The strength of two indicators of social position on oral health among persons over the age of 80 years

OBJECTIVE: The objective of the present study is to analyze how two dimensions of social position, education and social class, are associated with oral health among generally healthy, community-dwelling persons over the age of 80 years. METHODS: The present investigation is based on a sample of 157 community-dwelling individuals from The Kungsholmen Elders Oral Health Study (KEOHS) and included data from interviews and oral examinations. Social position was measured by education and social class. Oral health was measured by active coronal caries, active root caries, edentulism and use of dental services. RESULTS: The primary findings of the adjusted multivariate logistic regression analysis were that, compared to persons who had been in higher positions, persons who had been blue-collar/ white-collar workers had significantly greater odds of having coronal caries and high, but nonsignificant odds of being edentulous. Further, persons with elementary/ medium education tended to forego regular dental services more than persons with high education. CONCLUSION: The study identified social inequalities in oral health even in a population of independently living, generally healthy very old Swedes and in a country where the public health policies have tried to minimize these inequalities.     

Occurrence of epithelial dysplasia in oral leukoplakia. Analysis and follow-up study of 12 cases.

The histologic material of 500 leukoplakia patients was analyzed in order to define the characteristics of epithelial dysplasia and to correlate the findings with the clinical data. Epithelial dysplasia was found in 120 cases (24 per cent) and was graded as mild, moderate, or severe. The occurrence of dysplasia was highest in the group of erosive leukoplakias. The majority of the severe dysplasias were found on the tongue and lips. Follow-up studies on sixty-eight leukoplakia patients with histologic dysplasia revealed carcinoma in nine cases (13.2 per cent) during the mean observation period of 6.3 years. Leukoplakias of the tongue showed the highest incidence of malignant change.     

Identification of salivary metabolites for oral squamous cell carcinoma and oral epithelial dysplasia screening from persistent suspicious oral mucosal lesions

Clinical Oral Investigations - To identify salivary metabolite biomarkers to differentiate patients with oral squamous cell carcinoma and oral epithelial dysplasia (OSCC/OED) from those with...     

Immunohistochemical study of syndecan-1 down-regulation and the expression of p53 protein or Ki-67 antigen in oral leukoplakia with or without epithelial dysplasia

BACKGROUND: Leukoplakia is an oral pre-cancerous lesion that sometimes develops into squamous cell carcinoma. Therefore, leukoplakia with epithelial dysplasia is useful for studying carcinogenesis at the cellular level. The purpose of this study was to evaluate a potential association between the loss of syndecan-1 expression and the expression of p53 protein and Ki-67 antigen, and to identify reliable markers for predicting malignant changes in oral leukoplakia with epithelial dysplasia. METHODS: Changes in the expression of syndecan-1, p53, and Ki-67 were examined immunohistochemically in 43 cases of oral leukoplakia with or without epithelial dysplasia. The subjects were categorized as: none, 13 cases; mild dysplasia, 5 cases; moderate dysplasia, 17 cases; and severe dysplasia, 8 cases. The expression of these molecules in normal oral epithelia (22 cases) was also investigated. RESULTS: Strong syndecan-1 expression was observed on the surface of keratinocytes in normal epithelium. Immunopositivity was lost gradually as the extent of epithelial dysplasia increased. In normal epithelium, p53 and Ki-67 appeared mainly in the basal cell layer, while they were more widely distributed in leukoplakia. Specifically, significant changes were observed in the labeling index of p53 and Ki-67 in leukoplakia as epithelial dysplasia progressed from mild to moderate or severe. CONCLUSION: Our results reveal that overexpression of p53 protein and Ki-67 antigen, and down-regulation of syndecan-1 expression in the lower part of the epithelium, are associated with dysplastic changes. Therefore, the down-regulation of syndecan-1 expression may be the most important reliable marker for dysplastic changes.     

Risk indicators for severe impaired oral health among indigenous Australian young adults

Background  

Oral health impairment comprises three conceptual domains; pain, appearance and function. This study sought to: (1) estimate the prevalence of severe oral health impairment as assessed by a summary oral health impairment measure, including aspects of dental pain, dissatisfaction with dental appearance and difficulty eating, among a birth cohort of Indigenous Australian young adults (n = 442, age range 16-20 years); (2) compare prevalence according to demographic, socio-economic, behavioural, dental service utilisation and oral health outcome risk indicators; and (3) ascertain the independent contribution of those risk indicators to severe oral health impairment in this population.     

Characterization of epithelial cell activity in patients with oral cancer

Accurate, predictive assessment of the clinical behaviour and progression of individual oral cancers and premalignant lesions requires reproducible and quantitative analyses of diseased tissue. In this paper we describe the use of in vitro double labelling (sequential tritiated thymidine and bromodeoxyuridine staining of proliferating epithelial cells) to calculate S phase labelling indices (LIs), estimation of S phase duration (tS), and measurement of variables of flux to and from S for excised specimens of oral squamous cell carcinoma, premalignant lesions, and clinically normal mucosa from patients with oral cancer. There was a significant increase in mean LIs in buccal mucosa leukoplakias (14.5%) compared with normal mucosa (10.3%); P = 0.03. LIs were also increased in patients with cancers of the floor of mouth and ventral tongue but neither these changes nor alterations in flux parameters or S Phase durations were significant. Twenty-one kinetic profiles of dysplastic and malignant tissue were compared with conventional histopathological results, however, and these showed a 2.2% increase in LIs with each increase in grade of dysplasia (P = 0.004) and a 12% increase in LIs with each reduction in tumour differentiation (P = 0.02).     

Knowledge of oral cancer risk factors and diagnostic concepts among North Carolina dentists. Implications for diagnosis and referral

BACKGROUND: Dentists play a critical role in the early detection of oral and pharyngeal cancer (OPC). The authors administered a survey that assessed the level of knowledge among dentists regarding risk factors and diagnostic concepts. METHODS: In 2002, the authors mailed a 38-item, pretested survey to a random sample of 1,115 licensed dentists practicing in North Carolina. Three-level (low, medium, high) composite index scores for knowledge of risk factors and diagnostic concepts were created using previously developed scales. The authors formulated multivariable models for risk factor and diagnostic knowledge indexes. RESULTS: Of the 584 respondents, only 181 (31 percent) had consistent medium-to-high levels of knowledge on both highly correlated indexes. Dentists who had higher risk factor and diagnostic knowledge scores were significantly (P < .05) more likely to have heard of one or more diagnostic aids (odds ratio [OR], 2.7), to have graduated from dental school within the previous 20 years (OR, 1.8) and to have performed biopsies or referred five or more patients with suspicious lesions per year (OR, 1.7 and 1.5, respectively) than were less-knowledgeable respondents. CONCLUSIONS: More education is needed in dental schools, postgraduate programs and continuing education programs to enhance dental professionals' knowledge of OPC risk factors and diagnostic concepts. Such programs should include information about adjunctive diagnostic aids. PRACTICE IMPLICATIONS: Greater knowledge of risk factors and diagnostic concepts may result in more frequent patient referrals, biopsy procedures or both, thus aiding in the early diagnosis and treatment of patients with OPC.     

Outcomes of oral squamous cell carcinoma arising from oral epithelial dysplasia: rationale for monitoring premalignant oral lesions in a multidisciplinary clinic

Surveillance of oral epithelial dysplasia results in a number of newly diagnosed cases of oral squamous cell carcinoma (SCC). The clinical stage of oral SCC at diagnosis influences the magnitude of treatment required and the prognosis. We aimed to document the stage, treatment, and outcome of oral SCC that arose in patients who were being monitored for oral epithelial dysplasia in a dedicated multidisciplinary clinic. Those with histologically diagnosed lesions were enrolled on an ethically approved protocol and molecular biomarker study. Details of clinical and pathological TNM, operation, radiotherapy, recurrence, second primary tumour, and prognosis, were recorded in patients whose lesions underwent malignant transformation. Of the 91 patients reviewed (median follow-up 48 months, IQR 18-96), 23 (25%) had malignant transformation. All were presented to the multidisciplinary team with stage 1 disease (cT1N0M0). Of these, 21 were initially treated by wide local excision, 2 required resection of tumour and reconstruction, and 2 required adjuvant radiotherapy. At follow-up 3 had local recurrence, one had regional recurrence, one had metachronous lung cancer, and 5 had second primary oral SCC. There were further diagnoses of oral dysplasia in 5 during follow-up, and it is estimated that 76% of patients will have one or other event in 5 years. Disease-specific survival was 100% and overall survival was 96% (22/23). Median follow-up after diagnosis of oral SCC was 24 months (IQR 11-58). Specialist monitoring of oral epithelial dysplasia by a multidisciplinary team allows oral SCC to be detected at an early stage, and enables largely curative treatment with simple and usually minor surgical intervention. The high incidence of second primary oral SCC in high-risk patients with oral epithelial dysplasia further supports intensive targeted surveillance in this group.     

Attitudes to oral health among adolescents with high caries risk

OBJECTIVE: To explore and describe attitudes to oral health among adolescents with high caries risk. MATERIAL AND METHODS: A strategic selection of 45 subjects (15 to 19 years of age) assessed with high caries risk were invited to participate in the study, and 7 girls and 10 boys gave their informed consent. Semi-structured interviews performed, recorded, and transcribed verbatim were evaluated using qualitative content analysis. RESULTS: Three categories and seven associated subcategories could be determined, and cognitive consistency in parallel with emotional inconsistency in relation to oral health was disclosed. On a cognitive level, attitudes to oral health were characterized by an awareness of the determinants (diet, plaque, fluoride) for caries. Fresh breath and even, white, teeth were considered signs of good oral health. Breath and esthetic appearance were important inducements for home care. Although toothbrushing was considered the most important activity for maintaining good oral health, forgetfulness and lack of time were the main reasons for not brushing. The provision of adequate information on caries risk was perceived as important. On the emotional level, the three subcategories were: (i) a positive attitude to oral health and clear self-confidence that improved health would be achieved, (ii) an impassive attitude that everything would be all right and fixed by the dentist, and (iii) a negative attitude characterized by frustration and a tendency to give up. CONCLUSIONS: Allowing adolescents with high caries risk to relate their views on oral health is important for dental professionals when encouraging patients at caries risk towards healthy behavior.     

Each portion of fruit or vegetable consumed halves the risk of oral cancer

DATA SOURCES: Medline was used to find relevant papers; reference lists of retrieved publications were also searched. STUDY SELECTION: Studies were included if they met all of the following criteria: 1) they contained original data from case-control or cohort studies; 2) the primary outcome was clearly defined as cancers of the mouth, pharynx and hypopharynx (as defined by codes 141, 143-146,148 and 149 of the ninth revision of the International Classification of Diseases or other classifications that included these sites); 3) the exposure of interest was measured as servings (per day, week or month) of fruit, vegetables or both (other exposure measurements, such as mass per day, were excluded unless data were provided to transform information to servings per day); 4) they provided relative risk (RR) estimates and their 95% confidence intervals (CI), or sufficient data to calculate these parameters; 5) were published in the English language; and 6) were published before September 2005. If a study appeared in more than one article, data from the most recent publication were used for the statistical analysis. Studies restricted to oral cancer in subjects aged under 45 years were excluded. DATA EXTRACTION AND SYNTHESIS: Study quality was assessed and data were extracted independently by two investigators, differences being resolved by discussion. All studies were stratified by fruit or vegetable intake to evaluate any dose-response relations, and some of the studies were used to perform multivariate analyses to adjust for several confounders. Separate meta-analyses were conducted for fruit and vegetable consumption. Potential sources of heterogeneity between the studies were examined using the DerSimonian and Laird method. Sensitivity analyses and a multivariate metaregression analysis were performed to examine observed heterogeneity. RESULTS: A total of 71 potentially relevant studies were identified: 16 were included in the meta-analysis. Seven studies had been carried out in Europe, five in the Americas and four in East Asia. Three case-control studies consisted solely of men and one study consisted solely of women. The pooled data allowed 65 802 and 57 993 subjects, respectively, to be included in analysis of fruit and vegetable consumption. The combined adjusted odds ratio (OR) estimates based on 16 studies showed that each portion of fruit consumed per day had a statistically significant effect, reducing the risk of oral cancer by 49% (OR, 0.51; 95% CI, 0.40-0.65). A similar effect was seen for vegetable consumption, with a significant reduction in the risk of oral cancer of 50% (OR, 0.50; 95% CI, 0.38-0.65). Homogeneity testing found a statistically significant heterogeneity for fruit consumption and vegetable consumption studies. This was examined using sensitivity analysis which did not substantially modify the main findings of the meta-analysis. CONCLUSIONS: The consumption of fruit and vegetables was found to be associated with a reduced risk of oral cancer. Prospective studies are needed to confirm this result.     

Management of oral health in persons with HIV infection.

Prevention and treatment of oral disease is required to maintain quality of life and to improve prognosis of patients infected with the human immunodeficiency virus (HIV). Management requires a team approach, and close collaboration with the appropriate responsible physicians and other health care workers is necessary. Oral infection is frequent and usually opportunistic, and management is based on certain principles. Infections may disseminate and can be persistent and severe; multiple concurrent or consecutive infections with different microorganisms are frequent; fungal, viral, and parasitic infections are rarely curable; and long-term antimicrobial therapy may be required. This article reviews the management of oral candidiasis, hairy leukoplakia, and infections with herpes simplex virus, varicella-zoster virus, and cytomegalovirus. The management of Kaposi's sarcoma, lymphomas, aphthous ulceration, gangrenous stomatitis, bleeding, xerostomia, and adverse drug reactions is also described. Treatment should avoid further immunosuppression and inducement of xerostomia or caries, and should be designed to avoid adverse drug reactions and possible drug interactions.