Has the 8th American joint committee on cancer TNM staging improved prognostic performance in oral cancer? A systematic review.

BACKGROUND: The 8th edition of the American Joint Committee on Cancer (AJCC) classification has introduced two new parameters: depth of invasion (DOI) and extranodal extension (ENE). The aim of this systematic review was to determine whether this 8th edition referred to oral squamous cell carcinoma (OSCC) offers performance superior to that of the 7th edition in relation to overall survival (OS) and disease-specific survival (DSS). MATERIAL AND METHODS: The review was carried out following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. The PubMed (MEDLINE), Scopus and Cochrane Library databases were searched covering the period up until April 7th, 2022. RESULTS: Thirteen retrospective cohort studies were finally included. The introduction of DOI and ENE in the 8th edition of the AJCC classification resulted in improved prognostic performance of the classification. CONCLUSIONS: Patients with OSCC can be better classified in relation to OS and DSS, while maintaining the simplicity and ease of use of the classification. This allows more appropriate treatment protocols to be applied and affords a better estimation of the prognosis of each patient.

Epidemiological, clinical, and prognostic analysis of oral squamous cell carcinoma diagnosed and treated in a single hospital in Galicia (Spain): a retrospective study with 5-year follow-up.

BACKGROUND: Oral cancer is a common neoplasm worldwide, mostly corresponding to squamous cell carcinoma (OSCC). Unfortunately, its overall prognosis remains poor, with no improvement in recent decades. In this study, we have analysed the epidemiological, clinical, and prognostic characteristics of OSCC on patients of a specific Spanish region (Galicia), in order to improve its prognosis and apply effective preventive and early diagnosis measures. MATERIAL AND METHODS: We retrospectively analysed 243 cases of OSCC, diagnosed and treated in a single hospital centre in Galicia between 2010 and 2015 (minimum of 5 years of evolution). Overall and specific survival were calculated (Kaplan-Meier) and associated variables were identified (log rank test and Cox regression). RESULTS: The mean age of the patients was 67 years, with the majority being male (69.5%), smokers (45.9%) and alcohol consumers (58.6%), who lived in non-urban areas (79.4%). Cases diagnosed at advanced stages entailed the 48.1% of the sample, and 38.7% of cases relapsed. The 5-year overall and disease-specific survival rates were 39.9% and 46.1%, respectively. Patients who consumed tobacco and alcohol had a worse prognosis. OSCC cases referred to hospital by specialist dentists had a better prognosis, as those who were previously diagnosed with an oral potentially malignant oral disorder (OPMD) or received dental care during OSCC treatment. CONCLUSIONS: In view of these findings, we conclude that OSCC in Galicia (Spain) still has a very poor overall prognosis, which is mainly related to the advanced age of the patients and the late diagnosis. Our study highlights the better survival of OSCC in relation to the referring health professional, the presence of a previous OPMD and the dental care after diagnosis. This demonstrates the importance of dentistry as a health profession involved in the early diagnosis and multidisciplinary management of this malignant neoplasm.

Periodontal health in a population with Parkinson's disease in Spain: a cross-sectional study.

BACKGROUND: The aim of this research is to evaluate the periodontal health of patients with Parkinson Disease (PD) in a Spanish cohort. MATERIAL AND METHODS: A cross-sectional study was performed on 104 patients with PD (mean age: 66.19+9.3 years) and 106 controls (mean age: 59.26+14.11 years). A pre-designed clinical protocol was implemented, which included a standardized epidemiological index for periodontal disease (CPITN), clinical attachment loss (CAL), tooth-loss, full mouth plaque index (FMPI), and oral hygienic habits. Univariate descriptions and comparative analysis were performed. RESULTS: The majority of PD patients presented good oral hygienic habits. There were no significant differences in relation to CPITN, periodontitis, gingival recessions and tooth loss. However, moderate/severe CAL (p=0.027) and FMPI (p=0.003) was higher in the PD group. CONCLUSIONS: There were no differences on periodontitis and tooth loss between both groups. The higher number of advanced CAL and presence of biofilm in the PD group could be related to the difficulties to perform an effective tooth brushing due to this neurological disorder.

Facts and controversies regarding oral health in Parkinson's disease: A case-control study in Spanish patients.

BACKGROUND: Parkinson's disease (PD) is one of the leading neurological disorders, affecting more than 6 million people worldwide. These patients present motor and non-motor symptoms, including oral pathology. The objective of this research is to determine the oral health of patients diagnosed with PD, in order to stablish a specific preventive oral health programme. MATERIAL AND METHODS: Case-control study on 104 PD and 106 control patients. The pre-designed clinical protocol included a complete oral examination on general aspects, standardised epidemiological index for caries, periodontal disease and edentulism, analysis of oral hygiene, presence of mucous/ salivary/ functional disorder, and dental treatments. RESULTS: A higher number of PD patients consumed daily sweets (p<0.004) and antidepressant drugs (p<0.004). Patients with PD practised less interdental hygiene (p<0.023). The mean plaque index was higher in PD (p<0.003). Drooling (p<0.001), xerostomia (p<0.001), hyposialia (p<0.001), dysphagia (p<0.001), hypogeusia/dysgeusia (p<0.025) and chewing difficulty (p<0.006) were more common in PD. CONCLUSIONS: Oral disorders are frequent in PD. A good knowledge of these alterations will allow us design a specific preventive protocol. Some oral alterations may be a sign of diagnostic alert or progression of PD.

Capsaicin intake and oral carcinogenesis: A systematic review.

BACKGROUND: Chili is the most heavily and frequently consumed spice, either as a flavouring or colouring agent, and it is also a major source of pro-vitamin A, vitamin E and C. The main capsinoidcapsaicinoid found in chili peppers is capsaicin. It has been demonstrated that capsaicin acts as a cancer-suppressing agent through its antioxidant and anti-inflammatory effects, by blocking several signal transduction pathways. Oral squamous cell carcinoma is one of the most prevalent cancer worldwide. It is noteworthy that in countries where populations of diverse ethnic groups co-exist, differences have been observed in terms of incidence of oral cancer. The variances in their diet could explain, at least in part, these differences. The objective of this systematic review is to explore if there is evidence of a possible relationship between capsaicin intake and the incidence of oral squamous cell carcinoma, and discuss such association. MATERIAL AND METHODS: A bibliographical search was made in PubMed, Scopus and Web of Science databases, and finally 7 experimental studies were included; OHAT risk of bias tool was used to assess their quality. RESULTS: allAll the studies confirm that capsaicin is a chemopreventive agent that prevents the development of oral cancer, through inhibition of malignant cell proliferation and increase of apoptosis. CONCLUSIONS: More human studies are needed in order to clarify the real link between consumption of chili (capsaicin) and the prevalence of oral cancer.

Clinical presentation of burning mouth syndrome in patients with oral lichenoid disease.

BACKGROUND: To analyze the presence of burning mouth syndrome (BMS) in a group of patients diagnosed with oral lichenoid disease (OLD). MATERIAL AND METHODS: A retrospective study of 217 patients diagnosed with OLD; 158 (72,8%) women and 59 (27,2%) men, with an average age upon diagnosis of 56,4 years (SD 11,88). We carried out a detailed and complete characterization of symptoms, with special emphasis on BMS diagnostic data specified by the International Headache Society. RESULTS: Four patients (1.8%) presented with long-term clinical symptoms of burning mouth, indicative of BMS and they fulfilled the IHS 2018 criteria, except for criterion D, i.e."Oral mucosa is of normal appearance". The observed lichenoid mucosal lesions were not considered to be able to account for the reported intraoral pain in any of our patients. Thus neither diagnosis was considered to be exclusive. CONCLUSIONS: Patients diagnosed with OLD, and who simultaneously present clinical characteristics of BMS should be studied in detail, in order to evaluate the possibility of both diagnoses concurring.

Clinicopathological and prognostic characterization of oral lichenoid disease and its main subtypes: A series of 384 cases.

BACKGROUND: To clinicopathologically characterize the diagnosis of oral lichenoid disease (OLD) and its main subtypes: oral lichen planus (OLP) and oral lichenoid lesion (OLL), in order to correctly asses their prognosis. MATERIAL AND METHODS: Ambispective cohort study of 384 patients with diagnosis of OLD, based on pre-established clinical and histopathological criteria. We have analysed 272 (70.8%) women and 112 (29.2%), whose mean age was 57.1+/-11.8 years (range 21-90); minimum follow-up time was 36 months. A specific protocol was designed for this study, where we gathered the data of each patient, including malignant transformation. RESULTS: OLP was diagnosed in 229 cases (77.9%) and OLL in 85 (22.1%). Tobacco consumption was found in 20.3% of the patients and alcohol intake in 41.1%. Liver pathology was present in 10.7% of the cases, thyroid pathology in 11.5%, arterial hypertension in 15.6%, diabetes mellitus in 7.6%, psycho-emotional disorders in 33.3%, skin involvement in 12% and genital involvement in 4.9%. Ten patients (2.6%) developed an oral squamous cell carcinoma, 5 (1.7%) with OLP and 5 (5.9%) with OLL. CONCLUSIONS: OLD is a potentially malignant disorder of the oral mucosa which has to be correctly diagnosed as either OLP or OLL, since the risk of malignancy of these subtypes is significantly different.

Peri-implant peripheral giant cell lesions: report of 13 new cases and comparative histological and immunohistochemical analysis with peripheral and central giant cell lesions.

BACKGROUND: Few cases or peri-implant peripheral giant cell lesions (PGCL) have been reported in the literature. The aim of this study was to report 13 new cases of peri-implant PGCL and compare the expression of smooth muscle actin, Bcl-2 protein, GLUT-1, CD68, osteoprotegerin, receptor activator of nuclear factor kappa-B, Ki-67 and CD34 in these cases with PGCL and central giant cell lesions (CGCL). MATERIAL AND METHODS: Clinical data were retrieved from the laboratory records and histological analysis was performed using HE-stained slides. Immunohistochemical reactions for the above mentioned antibodies were performed and digitally scored. RESULTS: Peri-implant PGCL mostly affected the posterior mandible of adult females. CD68 and Bcl-2 expressions were higher in conventional PGCL and CGCL than in peri-implant PGCL ( p=0.033 for CD68 and p<0.0001 for Bcl-2). Microvessel density was higher in conventional peripheral than in central and peri-implant PGCL ( p=0.002). Proliferative index of the mononuclear cells showed no statistically significant differences comparing the three groups but it was higher in peri-implant PGCL. CONCLUSIONS: The current study demonstrated that peri-implant PGCL is more common in the posterior mandible of adult females. There were some differences in microvessel density, proliferative activity and expression of CD68 and Bcl-2 among conventional PGCL, peri-implant and CGCL. Further studies are encouraged to better understand these early findings.

Validation of microRNA expression profile in Oral Lichenoid Disease through cytological samples.

BACKGROUND: To validate oral exfoliative cytology in the analysis of the microRNA expression profile in Oral Lichenoid Disease (OLD). MATERIAL AND METHODS: The expression of 13 microRNAs identified and presented by our group in a previous study was analyzed in 26 cases, 16 diagnosed as OLD and 10 controls with no oral mucosal pathology. Cytological samples from the oral mucosa obtained using an Orcellex toothbrush were analyzed using RT-qPCR and TaqMan microRNA assays. RESULTS: The aberrant expression was validated for 2 microRNAs (miR-146a-5p and miR-7-1-3p) of those previously recognized in the biopsy study. CONCLUSIONS: This is the first time that oral exfoliative cytology is validated in a study of the alterations of the expression of microRNAs in OLD. The alteration of miR-146a and miR-7 compared to controls was validated. These microRNAs are associated with both inflammatory and carcinogenic phenomena that are involved in the etiopathogenesis of this potentially malignant oral disorder.

Benign epithelial oral lesions - association with human papillomavirus.

BACKGROUND: The presence of human papilloma virus in benign oral lesions has been studied by different techniques obtaining extremely variable results. The objective of this study was to determine the presence of human papillomavirus in 83 cases of benign hyperplastic epithelial oral lesions. MATERIAL AND METHODS: Eighty-three oral lesions with clinical or histopathological features suggestive of HPV infection were retrieved from the files of four oral pathology services. Demographic data were obtained from patient's medical charts. All cases had available clinical image, H&E preparations and paraffin blocks with enough tissue for HPV detection by in situ hybridization, and immunohistochemical reactions for Ki67. RESULTS: Episomal positivity for wide spectrum HPV was observed in 24% of the cases; most of them (70%) HPV 6/11 positive. HPV 16/18 was not detected. Condyloma acuminatum was the most common lesion associated with HPV (75%), followed by verruca vulgaris (15%), squamous papilloma and multifocal epithelial hyperplasia, 5% each. Koilocytes were identified in all the HPV positive cases. Ki67 showed an abnormal proliferation pattern in 90% of the HPV positive cases; most of them (70%) showing groups of proliferating cells in focal superficial regions, and in 20% positivity was seen almost in the whole thickness of the epithelium. HPV negative cases showed Ki67 positive cells restricted to the basal layer. CONCLUSIONS: Regarding oral lesions associated with HPV, condyloma is the most common lesion expressing low-risk subtypes. The etiology of squamous papilloma remains controversial as HPV was found in 1.9% of the cases. The identification of koilocytes and the pattern of expression of Ki67 reflect HPV infection and are helpful for classification. Papillary oral lesions not associated to HPV deserve further studies to better clarify its etiology.

Evaluation of the osteoclastogenic process associated with RANK / RANK-L / OPG in odontogenic myxomas.

BACKGROUND: Odontogenic myxoma (OM) is a benign intraosseous neoplasm that exhibits local aggressiveness and high recurrence rates. Osteoclastogenesis is an important phenomenon in the tumor growth of maxillary neoplasms. RANK (Receptor Activator of Nuclear Factor κappa B) is the signaling receptor of RANK-L (Receptor activator of nuclear factor kappa-Β ligand) that activates the osteoclasts. OPG (osteoprotegerin) is a decoy receptor for RANK-L that inhibits pro-osteoclastogenesis. The RANK / RANKL / OPG system participates in the regulation of osteolytic activity under normal conditions, and its alteration has been associated with greater bone destruction, and also with tumor growth. OBJECTIVES: To analyze the immunohistochemical expression of OPG, RANK and RANK-L proteins in odontogenic myxomas (OMs) and their relationship with the tumor size. MATERIAL AND METHODS: Eighteen OMs, 4 small (<3 cm) and 14 large (> 3cm) and 18 dental follicles (DF) that were included as control were studied by means of standard immunohistochemical procedure with RANK, RANKL and OPG antibodies. For the evaluation, 5 fields (40x) of representative areas of OM and DF were selected where the expression of each antibody was determined. Descriptive and comparative statistical analyses were performed with the obtained data. RESULTS: There are significant differences in the expression of RANK in OM samples as compared to DF (p = 0.022) and among the OMSs and OMLs (p = 0.032). Also a strong association is recognized in the expression of RANK-L and OPG in OM samples. CONCLUSIONS: Activation of the RANK / RANK-L / OPG triad seems to be involved in the mechanisms of bone balance and destruction, as well as associated with tumor growth in odontogenic myxomas.

MicroRNAs expression profile in solid and unicystic ameloblastomas.

OBJECTIVES: Odontogenic tumors (OT) represent a specific pathological category that includes some lesions with unpredictable biological behavior. Although most of these lesions are benign, some, such as the ameloblastoma, exhibit local aggressiveness and high recurrence rates. The most common types of ameloblastoma are the solid/multicystic (SA) and the unicystic ameloblastoma (UA); the latter considered a much less aggressive entity as compared to the SA. The microRNA system regulates the expression of many human genes while its deregulation has been associated with neoplastic development. The aim of the current study was to determine the expression profiles of microRNAs present in the two most common types of ameloblastomas. MATERIAL & METHODS: MicroRNA expression profiles were assessed using TaqMan® Low Density Arrays (TLDAs) in 24 samples (8 SA, 8 UA and 8 control samples). The findings were validated using quantitative RTqPCR in an independent cohort of 19 SA, 8 UA and 19 dentigerous cysts as controls. RESULTS: We identified 40 microRNAs differentially regulated in ameloblastomas, which are related to neoplastic development and differentiation, and with the osteogenic process. Further validation of the top ranked microRNAs revealed significant differences in the expression of 6 of them in relation to UA, 7 in relation to SA and 1 (miR-489) that was related to both types. CONCLUSION: We identified a new microRNA signature for the ameloblastoma and for its main types, which may be useful to better understand the etiopathogenesis of this neoplasm. In addition, we identified a microRNA (miR-489) that is suggestive of differentiating among solid from unicystic ameloblastoma.

The role of microRNAs in oral lichenoid disorders. Systematic review.

BACKGROUND: Certain changes in the microRNA expression are considered to be associated with chronic inflammatory processes and with the malignant transformation of oral potentially malignant disorders. The purpose of this systematic review is to update the existing data on the aberrant microRNA expression profiles identified in oral lichenoid disease (OLD). MATERIAL AND METHODS: A search in PubMed-Medline and Scopus was performed on the English literature published between 2010 and August 2016 using the following keywords: oral lichenoid disease, oral lichen planus and microRNA. RESULTS: Originally, 25 articles were considered, of which 12 case-control articles were selected according to the inclusion/exclusion criteria. CONCLUSIONS: OLD seems to have altered microRNA expression profile. Certain altered microRNAs (146a, 155) may be useful as biomarkers for this disorder. More studies including larger number of cases are needed in order to study further on the biological processes and on the regulation pathways of these altered microRNAs.

Histopathological characterization of the oral lichenoid disease subtypes and the relation with the clinical data.

BACKGROUND: The aim of the study was to analyze the histopathological characteristics of samples with a diagnosis of oral lichenoid disease (OLD) and their link with the location and the type of clinical lesion, and the clinicopathological subtypes. MATERIAL AND METHODS: Retrospective study on 85 consecutive patients diagnosed with OLD (58 women and 27 men, mean age of 57.7 years). Clinical and histopathological characterization of each case (modified WHO criteria). Collection of the clinical and histopathological data of the lesions. Descriptive and comparative statistical analysis of the results. RESULTS: The 78.8% of the cases were considered clinically typical while the 21.2% were considered compatible. Histologically, 52.9% were classified as typical and 47.1% as compatible. Biopsies from "plaque-like" lesions presented hyperkeratosis (p>0.001) and epithelial dysplasia (p=0.06) more frequently. Furthermore, acute inflammation was more evident in erosive-ulcerative lesions (p=0.001). Differences regarding the location of the biopsy were statistically non-significant. However, 42.9% of the tongue biopsies showed epithelial dysplasia. CONCLUSIONS: The histopathological aspect of this disorder is not specific and does not allow us to differentiate between the main subtypes. Therefore, the main reasons to perform a biopsy in this disorder are to define the differential diagnosis and to rule out epithelial dysplasia or a carcinoma. The final histopathological result may be subject to the type of lesion that is biopsied.

Genomewide miRNA profiling of oral lichenoid disorders and oral squamous cell carcinoma.

OBJECTIVE: To dissect the aberrant microRNA profile of oral lichenoid disorders (OLD) by analyzing the larger set of OLD samples tested so far. MATERIALS AND METHODS: MicroRNA expression profiles were assessed using TLDA card in 32 samples (16 OLD, 8 OSCC, and 8 control). The findings were validated using RT-qPCR in an independent cohort of 91 samples. RESULTS: We identified 20 differentially expressed microRNAs in OLD, of which several are functionally related to cell proliferation, response to organic substances, or immune processes. Further validation of the top-ranked microRNAs revealed that they were all aberrantly expressed in OLD. CONCLUSION: We have identified a new microRNA signature associated with OLD that may provide a meaningful basis for better understanding the physiopathology of the disease. In addition, we validated seven microRNAs whose expression was shown to be higher in OLD tissue in comparison with the control and OSCC tissues.

The use of tissue microarrays for semiquantitative evaluation of ATPaseC1 expression is ineffective.

We described earlier the possible role of ATPaseC1 expression as a diagnostic and prognostic marker for oral cancer; others have reported its use for tumors of the lung and breast. We assessed ATPaseC1 expression in a sample of oral squamous cell carcinoma (OSCC) using tissue microarrays (TMAs) to analyze the relation between ATPaseC1 expression and clinical, histopathological and prognostic parameters. We performed a retrospective study of 48 cases of OSCC. We constructed TMAs using two different regions of each tumor. V-ATPaseC1 immunohistochemistry was performed and assessed semiquantitatively. ATPaseC1 staining was observed in most of the neoplastic cells in all tumors. Staining was diffusely cytoplasmic and, to a lesser extent, nuclear. The degree of concordance between the measurements performed in tissue microarray 1 (TMA1) and tissue microarray 2 (TMA2), as evaluated using the intra-class correlation coefficient (ICC), was low. We found great variability in the immunohistochemical staining of the different regions of each tumor. We found 16 cases with mild expression (33.3%), 20 with moderate expression (41.7%) and 12 with intense expression (25%). Differences in the clinical-pathological variables studied were not statistically significant. The difficulty of immunohistochemical evaluation, the heterogeneity of the carcinomas and the fact that evaluation of expression requires semiquantitative analysis render the reliability of the results obtained from TMA-based techniques questionable.

Mucocutaneous leishmaniasis must be included in the differential diagnosis of midline destructive disease: two case reports.

Midline destructive lesions have multiple possible etiologies, which can be grouped into neoplastic, infectious, or vasculitis-associated. The purpose of these case reports and literature review was to highlight the need to include mucocutaneous leishmaniasis in the diagnosis of midfacial lesions in any patient who has lived in Leishmania-endemic areas because this entity meets all of the clinical criteria to be considered a form of midline destructive lesion. We present two cases of mucocutaneous leishmaniasis that occurred in a Bolivian male immigrant and a European male traveler to Panama, in whom lesions were misdiagnosed as different midline destructive lesions with different causes (Wegener, vasculitis, and natural killer or T-cell lymphoma [NKTL]). The conclusion of our work is that all patients with midline destructive lesions should undergo histologic and molecular studies to be evaluated for mucosal leishmaniasis, particularly patients whose clinical history suggests this possibility. In cases of uvular involvement, biopsy of this region might be a possible alternative to nasal biopsy.

Global DNA methylation: uncommon event in oral lichenoid disease.

OBJECTIVES: Accumulating evidence indicates that aberrant DNA methylation is closely related to oral carcinogenesis, and it has been shown that methylation changes might be used as prognostic biomarker in oral squamous cell carcinoma. Oral lichenoid disease (OLD) is the most common oral potentially malignant disorder in our region. The aim of this study was to perform the first wide DNA methylation study in OLD in order to investigate the relevance of DNA methylation changes in this premalignant disorder. MATERIALS AND METHODS: Two different Illumina microarray platforms, namely the GoldenGate Cancer Panel I and the HumanMethylation27 DNA Analysis BeadChip, were utilized in the discovery phase to interrogate the methylation profile of 59 OLD cases and 9 healthy individuals. Top-ranked genes were further validated by pyrosequencing in a second sample set consisting of 160 OLD and 65 controls. RESULTS: Our results show that the frequency of aberrant DNA methylation is rare in OLD, and this finding was further corroborated by pyrosequencing in the biological validation. CONCLUSIONS: These findings reinforce the notion that molecular alterations associated with oral carcinogenesis do not seem to be common events in OLD, which in turn might explain the low rate of malignization of this disorder.

Urban legends series: oral candidosis.

Candida species (spp) are commensal yeast that can only instigate oral infection (oral candidosis - OC) when there is an underlying predisposing condition in the host. We investigated four controversial topics on OC: (i) How can a microbiological determination of OC be made as Candida spp. are commensal yeasts and not all of them form hyphae or pseudohyphae during infection? (ii) Is median rhomboid glossitis (MRG) a manifestation of candidal infection? (iii) Can candidal infection cause palate papillary hyperplasia (PPH)? (iv) What is the best therapeutic treatment for denture-associated erythematous stomatitis (DAES)? Results from extensive literature searches, including a systematic review, suggested the following: (i) the diagnosis of OC merely on the basis of the presence of yeasts is an oversimplification of a complex process. No convincing evidence of a single test or method better able to discriminate the transition from candidal saprophytism to pathogenicity has been reported in the literature; (ii-iii) conclusive evidence of a direct aetiopathogenic relationship between MRG and PPH and candidal infection has not been found; and (iv) only limited evidence is available for any DAES treatment, thus making it impossible to make strong therapeutic recommendations.