Impaired intratumoral dendritic cell function and potential predictive value of dendritic cell markers for metastasis in malignant salivary gland tumors.

BACKGROUND: The differentiation between primary and metastatic salivary gland neoplasms (SGNs) helps in determining appropriate management strategies, including the need for additional diagnostic tests, surveillance, or aggressive treatment. The purpose of this study was to identify and quantify the immature and mature dendritic cells (DCs) in metastatic and no metastatic SGNs and determine its association with clinicopathological findings. MATERIAL AND METHODS: Cross-sectional, observational, and descriptive study that includes 33 malignant salivary gland neoplasms [MSGN (6, 18.1% metastatic)], and 22 pleomorphic adenomas (PA), as a control group. Clinical and histopathological characteristics were obtained. Immunohistochemistry for human leukocyte antigen D-related (HLA-DR), CD1a, CD83, and Ki-67 proteins was done. Positive intra- and peritumoral DCs were counted. RESULTS: Individuals with MSGN had a lower density of intratumoral HLA-DR+ cells than those with PA (p=0.001), Ki-67 immunostaining was significantly higher in MSGN than in PA (6% vs. 1.4%, p<0.001). Metastatic MSGN showed less intratumoral CD1a+ than non-metastatic (3.2 vs. 165.1, p=0.001). No differences in intra- and peritumoral CD83+ cells were found between benign and malignant SGN. CONCLUSIONS: These results suggest that the immune-protective function of intratumoral DCs is compromised in MSGNs. DCs markers may represent useful prediction tools for metastases in salivary gland malignancies, with crucial implications in the implementation of appropriate disease management strategies.

Primary oral and sinonasal mucosal melanomas in Latin America: a systematic review.

Primary oral and sinonasal mucosal melanomas (POSNMMs) are aggressive neoplasms with limited therapeutic alternatives. The aim of this review was to characterize the demographic, clinical, immunohistochemical, and molecular information regarding these tumors in the Latin American population. Articles published in English, Spanish, or Portuguese (1990-2022) retrieved from the PubMed/MEDLINE, Scopus, CAS, Web of Science, EBSCO, and Google Academic databases were included. Thirty-three studies, with a total of 1212 cases, were identified. Clinicopathological data were available for 870 cases and immunohistochemical and/or molecular information for 342. Nineteen studies (57.6%) reported cases of oral melanoma, three (9.1%) sinonasal melanoma, and 11 (33.3%) oral and sinonasal melanoma. Fifteen studies (45.5%) provided only clinicopathological data, 12 (36.4%) reported only immunohistochemical data, two (6.1%) shared clinicopathological and immunohistochemical data, one (3.0%) offered clinicopathological, immunohistochemical, and molecular data, one (3.0%) provided immunohistochemical and molecular data, one (3.0%) clinicopathological and molecular data, and one (3.0%) only molecular data. The mean age of individuals with POSNMMs was 58 years, and slightly more were male (male 51.3%, female 48.7%). In Latin America, POSNMMs are a rare but aggressive malignancy with a poor prognosis and limited treatment options. Although molecular data and targeted therapy are still being researched, data from Latin America indicate the need for multicenter collaborative clinical trials to unite individual and isolated efforts.

Human papillomavirus load in benign HPV-associated oral lesions from HIV/AIDS individuals.

BACKGROUND: Although HPV emerged as a crucial carcinogenic and prognostic biomarker in head and neck cancer, and considering the increase in HPV-associated oral lesions (HPV-OLs) in HIV individuals, molecular information about HPV-OLs is scarce; thus, our aim was to determine viral loads in HPV-OLs from HIV/AIDS individuals. METHODS: HIV/AIDS subjects with HPV-OL were included in this cross-sectional study. Following informed consent, biopsies were obtained. HPV detection and typing were carried out by PCR and sequencing (MY09/11, GP5+/6+). HPV-13 and HPV-32 loads were determined by a high-resolution melting assay. For statistical analysis, X2 , Fisher's exact, and Mann-Whitney U tests were applied, using SPSS software (v.23). RESULTS: Twenty-nine HIV subjects (median age 38 years, 93% males) were included. Most were AIDS individuals (72.4%) under HAART (89.7%). Twenty-two (75.9%) participants had more than one HPV-OL (four with florid presentations), mostly multifocal epithelial hyperplasia (62%), being HPV-13 (26%) and HPV-32 (31%) the most frequent types. HPV load was higher in individuals with multiple HPV-OLs than in solitary lesions (4.9 vs. 3.2 Log10 copies/ml, p = .090) and in HPV-32+ than in HPV-13+ (8.3 vs. 6.4 Log10 copies/ml, p = .014). CONCLUSIONS: Multiple HPV-OLs showed high HPV loads, possibly indicating transcriptional activity of the virus; however, in the HIV setting, the individual and local immunological response could be the key process.

Double-blind placebo-controlled randomized clinical trial evaluating doxycycline effects on chemotherapy-induced oral mucositis.

WHAT IS KNOWN AND OBJECTIVE: Chemotherapy (CT)-associated oral mucositis (OM) is one of the most debilitating and painful side effects in oncology patients, with limited effective management options. During CT, matrix metalloproteinases (MMPs) are upregulated, causing damage in mucosal and submucosal tissues, and playing a key role in OM; therefore, the use of subantimicrobial doxycycline as a MMP inhibitor may represent a potential approach for OM management. The aim of this clinical trial was to evaluate the efficacy and safety of low doses of doxycycline in OM development in individuals with acute leukaemia (AL) during CT. METHODS: Randomized controlled clinical trial (Registration No. NCT01087476) performed in adult AL patients scheduled to receive CT (September 2010-October 2014). Individuals were stratified by leukaemia type and assigned randomly to receive doxycycline hyclate (50 mg/d) (doxycycline group: DG) or placebo (placebo group: PG) before and during CT. Included subjects had a baseline oral examination and thereafter 3 times a week during 21 days. The primary outcome was OM development. RESULTS AND DISCUSSION: One hundred and forty-seven AL subjects were enrolled: 74 in DG and 73 in PG; baseline characteristics between groups were comparable. During follow-up, 15 (10.2%) individuals developed OM; no differences between treatment groups were found (DG:8.1%, PG:12.3%; P = .59). The mean OM Assessment Scale score was 2.51, without differences between groups (DG:2.7, PG:2.4; P = .65). Low baseline blood albumin levels in the OM-affected individuals were identified, revealing the effect of systemic deterioration as a predisposing factor for OM development. No adverse effects were observed. WHAT IS NEW AND CONCLUSION: Subantimicrobial doses of doxycycline did not reduce the incidence, onset, duration or severity of OM.

Clinicopathological characterization of primary oral and sinonasal melanoma in a referral centre in Mexico City: 2000-2012.

In Mexico, there have been few studies on primary oral and sinonasal melanoma, an aggressive neoplasm with a low survival rate and few therapeutic alternatives. Further, there is limited information about its clinical and histopathological characteristics. The aim of this retrospective study was to describe the clinicopathological profile of these tumours in patients attending a major oncology reference centre in Mexico City over a 12-year period. Demographic and clinical data were obtained from the clinical charts, and histopathological features were evaluated. χ(2), Fisher's exact, and Mann-Whitney U-tests were used for analysis; significance was set at P<0.05. Thirty-three cases were studied (73% sinonasal melanoma (SNM) and 27% oral melanoma (OM)); 58% were female and the median age was 66 (Q1-Q3 55.5-75) years. Compared with OM patients, SNM patients had a shorter time to diagnosis (16.7 vs. 11.7 months, P=0.022), were identified at earlier stages (33.3% vs. 58.3%, P=0.010), and all presented symptoms (66.7% vs. 100%, P=0.015). All samples showed vertical growth and 96.9% exhibited pleomorphism. A higher proportion of cases with pleomorphism developed metastases at follow-up than those without (60% vs. 12.5%, P=0.026). The present study provides valuable information that could form the basis of future studies in the search for advanced therapy modalities.

Association between age and high-risk human papilloma virus in Mexican oral cancer patients.

OBJECTIVE: Studies reporting low prevalence of HPV in OSCC with declining age at presentation are increasing. The aim of this study was to determine the prevalence of HPV in a group of OSCC cases and controls in a Mexican population. METHODS: The matched case-control study included 80 OSCC cases and 320 controls. HPV/DNA presence was evaluated through PCR amplification using three sets of consensus primers for the L1 gene. A conditional logistic regression analysis was carried out for the matched OSCC cases and controls. Interactions between risk factors and OCSS were tested in the construction process of the models. RESULTS: HPV prevalence was 5% in OSCC cases and 2.5% in controls. HPV-detected types were 16, 18 and 56. According to conditional logistics regression model, an association was detected between HR-HPV and OSCC. All HR-HPV-positive OSCC cases corresponded to young patients (<45 years), non-smokers and non-alcohol drinkers. CONCLUSIONS: The HR-HPV can be a contributing factor to oral carcinogenesis, especially in younger individuals without known risk factors such as tobacco and alcohol.

Clinical markers of immunodeficiency and mechanism of immune reconstitution inflammatory syndrome and highly active antiretroviral therapy on HIV: workshop 3A.

Antiretroviral therapy (ART) has improved survival and changed the disease pattern of HIV infection. However, ART may cause serious side effects, such as metabolic and cardiovascular complications. In addition, immune reconstitution inflammatory syndrome (IRIS) is being increasingly reported in relation to ART. The article presents the consensus of a workshop around 4 key issues: (1) the differences in the response of adults and children to highly active antiretroviral therapy, (2) the mechanism of the new HIV entry inhibitors and its effect on oral markers, (3) the pathogenesis of IRIS and the contradictory findings of the possible oral lesions related with IRIS, (4) and the benefits and barriers associated with using ART in the developing and developed world. The consensus of the workshop was that there is a need for future studies on the oral manifestations of HIV in individuals treated with new ARTs-especially, children. IRIS was considered a promising field for future research; as such, workshop attendees recommended formulating an IRIS-oral lesions case definition and following strict criteria for its diagnosis.

hMLH1 promoter methylation is an early event in oral cancer.

Promoter methylation is believed to inactivate the expression of hMLH1. This process has been implicated in the tumorigenesis of oral squamous cell carcinoma (OSCC). Thus, the aim of this study was to determine the profile of hMLH1 methylation and protein expression in OSCC. The matched case-control study included 50 OSCC cases and 200 controls, with a median of age 64 (Q1-Q3 54-71) years. Protein expression was determined by immunohistochemical staining, and hMLH1 gene promoter methylation was analyzed by methylation-specific polymerase chain reaction (MSP). A conditional logistic regression model for risk factors was built for OSCC cases and matched controls. Promoter methylation of hMLH1 was detected in 38 (76%) OSCC cases, but in none of the control samples. Of the 38 OSCC samples with promoter methylation, 12 (32%) were negative for hMLH1 protein, and corresponded to early clinical stages (10 in stage II and 2 in stage I). All 12 unmethylated samples showed positive stain for hMLH1. Multiple logistic regression analysis showed an OR of 16.54 (IC 95%: 1.69-161.68, p=0.016) for methylation of the hMLH1 gene and early stages of OSCC, adjusting by gender and tobacco use. This study showed a high frequency of hMLH1 promoter methylation that occurred in most of the early stage cases and in about half of the late stage cases. It is proposed that hMLH1 promoter methylation is an early event that is maintained during tumor progression.

Clinical, histological and immunohistochemical findings in oral Kaposi's sarcoma in a series of Mexican AIDS patients. Comparative study.

BACKGROUND: The origin of spindle cells (SC) in oral Kaposi's sarcoma (OKS) is still an intriguing aspect. Thus the aim of the present study was to compare the clinical, histological and immunohistochemical characteristics of OKS and oral pyogenic granuloma (OPG), in order to contribute to the knowledge of the cells involved in Kaposi's sarcoma pathogenesis. METHODS: In this retrospective, observational and comparative study, 39 OKS and 30 OPG cases were included. Immunohistochemical studies were performed for vimentin, alpha SMA, desmin, C-kit, CD34, D2-40 and LANA-1 [human herpesvirus-8(HHV-8)]. Statistical comparisons were done using the chi-square and Wilcoxon-Mann-Whitney rank sum tests. RESULTS: Fourteen (35.9%) OKS cases also affected the skin, and 83.8% involved the palate. All OKS and OPG were positive for vimentin and CD34. OKS samples were positive for alpha SMA, and 25.6% expressed C-kit. All OKS cases were positive for HHV-8, and the number of positive cells increased significantly from early / intermediate to late histological stage. D2-40 was expressed in the cellular component and vascular walls of all OKS cases, but it was negative in OPG. HHV-8 expression was increased in late histological stages of OKS lesions. CONCLUSIONS: The expression of D2-40 marker in the vascular walls and SC supports the view of a lymphatic differentiation in neoplastic cells of OKS. Desmin, alpha SMA, D2-40, C-kit and HHV-8 were the main markers differently expressed in OKS and OPG.

Mechanical deformation inhibits IL-10 and stimulates IL-12 production by mouse calvarial osteoblasts in vitro.

The skeleton is continuously remodelled throughout life, a process that is orchestrated by cells of the osteoblast lineage. Remodelling involves a complex network of cell-cell signalling involving systemic hormones, locally produced cytokines, growth factors and the mechanical environment of the cells. Here, we report on the effect of mechanically-induced strain on the synthesis by mouse calvarial osteoblasts in monolayer culture of IL-10 and IL-12, two cytokines that inhibit osteoclast formation in bone marrow cultures; IL-10 also suppresses osteoblast differentiation suggesting a role for both cytokines in bone physiology. A tensile strain was applied to the cells intermittently for 6s, every 90s, for 2-96h. After 2-h culture, supernatants from deformed cells contained significantly less IL-10 than control cultures. In contrast, mechanical deformation had a stimulatory effect on IL-12 synthesis; however, by 48h both had returned to control levels. These data suggest that IL-10 and IL-12 can be added to the growing list of mechanical stress-responsive genes. The down-regulation of IL-10 and stimulation of IL-12 further suggests that the initial response of the cells to mechanical deformation was an osteogenic one.

Intralesional vinblastine vs. 3% sodium tetradecyl sulfate for the treatment of oral Kaposi's sarcoma. A double blind, randomized clinical trial.

In this double-blind, randomized trial, we compared the clinical efficacy of intralesional vinblastine (VNB) and 3% sodium tetradecyl sulfate (STS) in the treatment of oral Kaposi's sarcoma (OKS). Subjects with OKS were randomly assigned to receive a single intralesional injection of either VNB or STS, at a standard dose (0.2 mg/cm(2)). Differences were evaluated by the Mann-Whitney U and Fisher's exact tests. Sixteen HIV-infected patients were included, eight received VNB and eight received STS; clinical response was evaluated at days 7, 14, and 28 following treatment. Tumor size reduction was 0.68 and 0.61 cm in the VNB and STS groups, respectively (P=0.80). Two VNB patients had complete or partial response whereas four STS subjects had partial responses (P=0.61). Patients in both groups experienced minimal toxicity. We conclude that intralesional vinblastine or STS are adequate for the management of OKS. The benefits of STS are its low cost and ease of use.

Frequency of oral conditions in a dermatology clinic.

BACKGROUND: Oral mucosal manifestations may be the initial feature, the most florid clinical feature, or the only sign of mucocutaneous diseases. METHODS: Sixty adult patients (48 women, 12 men) with oral mucous complaints were referred to and evaluated at a dermatology clinic in a tertiary care hospital in Mexico City between November 1996 and September 1998. RESULTS: The most frequent oral conditions observed were pemphigus vulgaris (18.3%), lichen planus (8.3%), candidiasis (8.3%), recurrent aphthous ulcers (6.7%), herpetic lesions (6.7%), xerostomia (6.7%), and traumatic lesions (6.7%). Oral affection in mucocutaneous conditions was observed in 21 (35%) patients; the diagnosis was based on oral signs in 10 (48%) of these patients. A large number of oral conditions had previously been misdiagnosed. CONCLUSIONS: The importance of the diagnosis of oral conditions in dermatology has been underlined in this study due to the frequency and diversity of oral lesions. The benefits of an interdisciplinary approach in the management of patients has been highlighted.

Thalidomide as therapy for human immunodeficiency virus-related oral ulcers: a double-blind placebo-controlled clinical trial.

A double-blind, randomized, placebo-controlled clinical trial was performed in Mexico City to evaluate the efficacy of thalidomide in treating oral recurrent aphthae in human immunodeficiency virus (HIV)-infected subjects. Sixteen HIV-infected patients with clinical and histological diagnosis of oral recurrent aphthous ulcerations received randomly an 8-week course of either thalidomide or placebo, with an initial oral dosage of 400 mg/d for 1 week, followed by 200 mg/d for 7 weeks. Ten subjects received thalidomide and six received placebo. At 8 weeks, nine subjects (90%) in the thalidomide group had complete healing of their ulcers, compared with two (33.3%) of the six patients in the placebo group (P = .03). There was a significant reduction in largest ulcer diameter in the thalidomide group. Rash was observed in 80% of the thalidomide patients. Although thalidomide demonstrated an unquestionable benefit in treatment of oral ulcers in HIV patients, caution must be taken given the frequent occurrence of side effects.

Oral manifestations of HIV infection by gender and transmission category in Mexico City.

A cross-sectional analysis was conducted in Mexico City from September 1989 to March 1996, to determine the prevalence of HIV-related oral manifestations by gender and route of HIV transmission. The diagnosis of HIV-associated oral lesions was based on preestablished criteria. For the statistical analysis chi-squared and Fisher's exact tests were used where appropriate. Odds ratios were calculated as estimates of the relative risks. Control of confounding factors was performed by logistic regression models. Oral lesions were present in 75% of 436 HIV+ patients. Hairy leukoplakia, erythematous and pseudomembranous candidosis, angular cheilitis and oral ulcers were frequently found. Patients who contracted HIV through blood transfusion were more likely to present erythematous candidosis (P=0.005) than subjects who acquired HIV through sexual transmission. Oral ulcers were seen only in men (P=0.02) and in individuals who contracted HIV through sexual transmission (P=0.02). This study brings valuable data in regard to differences in the type and prevalence of HIV-related oral lesions by gender and the risk categories analysed, particularly blood transfusion.

PIP: A cross-sectional analysis conducted in Mexico City, Mexico, in 1989-96 investigated the prevalence of HIV-related oral manifestations by gender and route of HIV transmission. The 436 HIV-positive patients enrolled in this study were part of a larger, ongoing study conducted through the Infectious Diseases Clinic in Mexico City. The primary mode of HIV transmission was blood transfusion among female respondents (63%) and sexual activity among male respondents (90%). 71% of subjects had at least 1 (mean, 1.3) HIV-related oral lesion, including hairy leukoplakia, erythematous and pseudomembranous candidosis, angular cheilitis, and oral ulcers. Candidosis, pseudomembranous candidosis, hairy leukoplakia, exfoliative cheilitis, and xerostomia were all significantly associated with a CD4 count under 200 cells/cu. mm and were more prevalent among those with advanced HIV disease. Oral ulcers were present only in men. Women had a higher prevalence than men of hyperpigmentation (10.5% vs. 4%) and xerostomia (7% vs. 2%), but these differences were not significant. Multivariate analysis revealed a significant association between erythematous candidosis and blood transfusion, even after controlling for gender, clinical stage, CD4 count, antiretroviral therapy, smoking history, and xerostomia.

Chemotherapy-associated oral mucosal lesions in patients with leukaemia or lymphoma.

In order to determine the incidence rate of oral lesions associated with chemotherapy, as well as well as its association with clinical and laboratory parameters and potential risk factors, 50 in-patients with non-Hodgkin's lymphoma or leukaemia under chemotherapy were followed from January 1993 to May 1994. Basal and weekly oral examinations were performed. Clinical and laboratory data were registered. Wilcoxon's rank sum test, chi square test, univariate and multivariate logistic regression analyses were used, 36 individuals with leukaemia and 14 with non-Hodgkin's lymphoma were followed for 158 weeks; mean age was 33 years (range 15-85). Oral lesion incidence rate was 45/100 patients-week. Exfoliative cheilitis and infections (herpes and candidosis) were the most common oral complications, followed by haemorrhagic lesions and mucositis. Haemorrhagic lesions correlated with thrombocytopenia (RR = 30.5). Etoposide administration (RR = 8.6), alkylating agents (RR = 15.6), a prior course of chemotherapy (RR = 23.2) and neutropenia (RR = 4.16) were predictors of mucositis. Oral lesions were a common complication in this study, and a possible association of mucositis with several factors is suggested.

Prognostic value of oral candidosis and hairy leukoplakia in 111 Mexican HIV-infected patients.

A follow-up study was carried out to evaluate the prognostic value of hairy leukoplakia (HL) and oral candidosis (OC) in a cohort of 111 asymptomatic Mexican HIV infected patients. Oral exams were performed at baseline and every 6 months, from September 1989 to March 1994. Chi-square contingency table test, the Kruskall-Wallis one-way analysis of variance, the Kaplan-Meier product-limit method and the log rank test were used for the analysis. Univariate and multivariate Cox's proportional hazards analysis were also performed. Fifty-four patients (51%) progressed to AIDS (initially 36 CDC-II and 18 CDC-III). Individuals with HL and/or OC, showed faster development to AIDS than subjects without lesions or other HIV-related manifestations (P = 0.008). The presence of OC, HL or both always remained significant despite adjustment for total lymphocytes, CDC stage, zidovudine therapy or its combinations. Oral lesions in HIV infection may be regarded with other clinical and laboratory studies as markers of HIV disease progression and as indicators to begin antiretroviral treatment.

Cancer of the mobile tongue in Mexico. A retrospective study of 170 patients.

Histological reports of 170 patients with cancer of the mobile tongue between 1977 and 1989 were identified at the Instituto Nacional de Cancerología (INCan), in Mexico City. Demographic, clinical and histological information was retrospectively reviewed. Chi-square, Student's t-test and Wilcoxon rank-sum test were applied for comparisons, and Kaplan-Meier curves, log-rank test and Cox proportional hazards for survival analysis. Of the 161 patients with mobile tongue squamous cell carcinoma (MTSCC), 104 (65%) were males and 57 (35%) were females. The mean age was 60 years old (range 19-91). T1 and T2 lesions comprised 35%, T3 and T4 lesions 65%. There was a statistically significant association between size of the tumour and lymph node involvement (P < 0.0001). The proportion of cases with advanced disease was 80% for males and 57% for females (P = 0.008). The 5-year survival rate was 16% (CI 10.2-22.8%). Cancer of the mobile tongue in Mexico still has a poor prognosis. Efforts should be made to reduce the delay in diagnosis of MTSCC, in order to increase the cure rates and improve the quality of life of the patients.

Oral findings in Mexican AIDS patients with cancer.

Oral findings of 42 Mexican AIDS patients with cancer were reviewed. Kaposi's sarcoma (KS) was the most frequent malignancy (81%) followed by non-Hodgkin's lymphoma (NHL) (12%). All cases of NHL were of high or intermediate grade and most of them were extranodal. Out of the 34 individuals with KS, 22 (65%) showed oral KS and in 21 of them the palate was involved. The clinical features of oral KS including site, appearance and size are described. Pseudomembranous candidosis (PC), hairy leukoplakia (HL) and exfoliative cheilitis (ECh) were also found in these patients. There was no association of these lesions with any type of cancer. A strong association of oral candidosis and history of this infection was found, RR = 7.0 (1.3-4.1). There was evidence of severe immunosuppression in most patients, with mean average CD4 counts of 116 mm3 (range 4-841/mm3). Oral KS, ECh, PC and HL were more common in patients with lower CD4 counts. Our findings illustrate the most frequent oral lesions associated with HIV-1 infection in patients with AIDS and cancer, and further support the importance of oral examination in HIV infected patients.