Search

Background: Proliferative verrucous leukoplakia is considered an uncommon oral potentially malignant disorder with a high malignant transformation rate. The objective of this paper was to define its cancer incidence and related risk factors.: Method: A retrospective audit of 34 patients diagnosed with proliferative verrucous leukoplakia from a university-based unit, during the period from 1995 to 2019 was performed. The mean number of visits was 23 ± 18.6. The follow-up was divided into four-time intervals to evaluate the clinical presentation, number of lesions, dysplasia grade, and malignant transformation rate. Results: The majority of patients were females 29 (85.3%), with verrucous component (77.8%), with a gingival presentation (31.8%), and with a preceding lichenoid area (44.1%). Eleven patients (32.4%) were affected by oral cancer during the follow-up, developing a total of 15 carcinomas. The mean age of malignant transformation was 67.2 ± 12.9 years, particularly 8 ± 8.5 from the onset of the lesions. Warty forms presented a higher mean estimate for malignant transformation (15.2 years, 95% confidence interval 4.4–26 years) than nodular forms (1.9 years, 95% confidence interval 1.9–1.9) (p = 0.019). Patients with an initial proliferative verrucous leukoplakia diagnosis suffered a higher risk of malignancy, particularly 15.55 times (95% confidence interval 1.69–143.17; p = 0.015) than those who did present a preceding area with lichenoid morphology. Conclusion: Proliferative verrucous leukoplakia presented a high malignant transformation rate and sometimes displayed preceding oral lichenoid areas in early stages. Further studies are needed to understand the impact of these lichenoid areas in proliferative verrucous leukoplakia progression SI

Oral squamous cell carcinoma (OSCC) is often preceded by a white patch on a surface of the mouth, called oral leukoplakia (OL). As accelerated telomere length (TL) shortening in dividing epithelial cells may lead to oncogenic transformation, telomere length measurement could serve as a predictive biomarker in OL. However, due to high variability and lack of a universal reference, there has been a limited translational application. Here, we describe an approach of evaluating TL using paired peripheral blood mononuclear cells (PBMC) as an internal reference and demonstrate its translational relevance. Oral brush biopsy and paired venous blood were collected from 50 male OL patients and 44 male healthy controls (HC). Relative TL was measured by quantitative PCR. TL of each OL or healthy sample was normalized to the paired PBMC sample (TL ratio). In OL patients, the mean TL ratio was significantly smaller not only in the patch but also in distal normal oral tissue, relative to healthy controls without a high-risk oral habit. Dysplasia was frequently associated with a subgroup that showed a normal TL ratio at the patch but significantly smaller TL ratio at a paired normal distal site. Our data suggest that evaluation of TL attrition using a paired PBMC sample eliminates the requirement of external reference DNA, makes data universally comparable and provides a useful marker to define high-risk OL groups for follow-up programs. Larger studies will further validate the approach and its broader application in other premalignant conditions.

The purpose of the study was to evaluate the prevalence of Oral Mucosal Lesions (OMLs) in an adult population from Santo Domingo, Dominican Republic. 751 subjects from eight communities from Santo Domingo accepted the invitation to participate in an oral screening from October 2016 to January 2017. 248 subjects were evaluated and clinically examined, age range 18-86 years. A validated instrument was designed to record demographic factors, age group, gender, anatomical location, presence or absence of OMLs, risk factors such as tobacco consumption and its frequency, and different forms of tobacco and alcohol use. A systematic oral clinical examination was conducted by a specialist. The presence or absence, and anatomic location of OMLs were recorded. The sample consisted of 44.4% males and 55.6 % females. 228 subjects had 1 or more lesions (91.9%), the median was 3 lesions per patient. In relation to risk factors, tobacco use in general was reported by 26.2 % of the subjects, with cigarette smoking reported by 75.4%, followed by other forms as "hookah" 9.2 %, marihuana 9.2%, cigars ("puros")4.6% and pipe smoking 1.5%. Among the oral lesions detected by screening, the nonpathological group was prevalent, and included physiologic melanin pigmentation as the most frequent (25.0%) followed by palatal/mandibular tori (20.2%), Fordyce granules (7.9%), and Exostosis (5.6%). Potentially malignant disorders (Oral Leukoplakia, Oral Lichen Planus and Actinic Cheilitis) corresponded to 2.2%, 0.3 %, and 0.3%, respectively. No malignancy was observed clinically. This study Authorutes to determining the prevalence of OMLs in Dominican Republic and to identifying risk factors. This is the first study reporting the prevalence of oral mucosal lesions among the Dominican adult population. This information is vital for establishing a public health program targeting the high-risk group to improve the oral health status in this population.El objetivo del presente estudio fue evaluar la prevalencia de lesiones de la mucosa oral (LMO) en una población adulta proveniente de Santo Domingo, República Dominicana. 751 individuos procedentes de ocho comunidades de la provincia de Santo Domingo, respondieron a la invitación para participar en el examen bucal, desde Octubre 2016 a Enero 2017. 248 sujetos con un rango de edad de 18-86 años, fueron evaluados y examinados clínicamente. Se diseñó y validó un instrumento para obtener datos de factores demográficos, grupos de edad, género, localización anatómica, presencia o ausencia de lesiones de la mucosa oral, factores de riesgo tales como: consumo de tabaco, frecuencia, diferentes formas de uso de tabaco y alcohol. Un especialista en el área, realizó un examen clínico bucal sistematizado en el cual se evaluó y registró la presencia o ausencia de lesiones y su localización anatómica. De acuerdo a la distribución por género, 44.4% correspondió a masculino y 55.6 % femenino. 228/248 sujetos presentaron 1 o más lesiones (91.9%), siendo la media de 3 lesiones por paciente. En relación a los factores de riesgo, el tabaco se reportó en 26.2%, siendo el fumar cigarrillos el 75.4%, seguido de otras formas como “hookah” 9.2%, marihuana 9.2%, cigarros (“puros”) 4.6% y pipa fumada 1.5 %. En cuanto a las lesiones bucales detectadas en el examen, el grupo de condiciones no patológicas fue el más frecuente e incluía a pigmentaciones fisiológicas melánicas (25.0%), seguida de torus palatino/mandibulares (20.2 %), gránulos de Fordyce (7.9%) y exostosis (5.6%),respectivamente. Las lesiones potencialmente malignas detectadas (Leucoplasia oral, Liquen plano oral y Queilitis actínica) correspondieron al 2.2%, 0.3 % y 0.3%, respectivamente. Clínicamente, no se observó malignidad. Este estudio Authoruye a determinar la prevalencia de LMO en República Dominicana e identificar factores de riesgo. Los hallazgos representan el primer estudio que muestra la prevalencia de las lesiones de mucosa oral en la población adulta dominicana. Se recomienda la creación de un programa de salud pública orientado a grupos de alto riesgo para mejorar el estatus de salud oral en esta población.

Lactate dehydrogenase (LDH) is an enzyme seen within every cell during their normal metabolic function. It is always confined within the cell cytoplasm and it becomes extracellular only when a cell dies. The extracellular presence of LDH is related to cell necrosis and tissue breakdown. Therefore, we designed a study to estimate and compare LDH levels in the saliva of patients with oral cancer, oral leukoplakia (OL), and smokers without lesions and in controls.A total of 81 subjects of both genders, between the ages of 20 and 70 years, were included in the study. The study group was divided into four: group I-controls (n = 20), Group II-smokers (n = 20), Group III-subjects with OL (n = 20), and Group IV-subjects with oral squamous cell carcinoma (OSCC) (n = 21). Five milliliters of unstimulated salivary sample was collected from each participant, and salivary LDH level was measured. The obtained values were tabulated and statistically analyzed. P0.05 was considered to be statistically significant.The difference in LDH levels among the four groups was found to "BE" statistically significant. LDH values showed a marked increase in the leukoplakia group (49.79 ± 19.88 IU/L) and OSCC group (106.97 ± 32.75 IU/L) when compared to controls and smokers.We found that salivary LDH was increased in patients with leukoplakia and OSCC. Smoking alone did not produce any alterations in salivary LDH. It is possible that salivary LDH could be a potential biomarker to identify early premalignant or malignant changes in smokers.

Objective Oral hairy leukoplakia (OHL) is a benign Epstein-Barr virus infection typically presenting as a white lesion on the lateral border of the tongue. Historically, OHL was described in patients who are severely immunocompromised, such as those with HIV/AIDS and organ transplant patients. OHL is increasingly seen in patients who are not severely immunocompromised. This study reviews 45 cases of OHL in a single institution and characterizes the clinical features of these relatively immunocompetent patients. Study Design Retrospective study. Results There were 45 cases with 23 male patients (51.1%) and a median age of 64 (range, 24-100 years). The lateral/ventral tongue was the affected site in 41 cases (91.1%), and 5 cases presented bilaterally. A review of the medical history and medications showed the most common conditions were hypertension (53.3%), hyperlipidemia (42.2%), and chronic respiratory conditions (33.3%); 8 patients (17.8%) had diabetes mellitus, and 1 had rheumatoid arthritis. Eleven cases (24.4%) reported no underlying medical conditions or history of medications. The most frequently reported medications included antihypertensive drugs (21.0%), steroid inhalers (14.6%), and cholesterol-lowering drugs (11.0%). Conclusions OHL is not exclusively seen in profoundly immunocompromised patients. Localized immunosuppression (from steroid inhalers) and immunosenescence (aging) are possible contributing factors.

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies in the head and neck with a poor prognosis. Oral cancer development is a multistep process involving carcinogenesis. Though significant advances in cancer immunotherapy over the years, there is lack of evidence for T-cell exhaustion during oral carcinogenesis. Clinical specimens from healthy donors and patients diagnosed with oral leukoplakia (OLK) or OSCC were collected for immunohistochemical staining with PD-L1, CD86, CD8, PD-1 and CTLA-4 antibodies. Meanwhile, chemically induced mouse models of oral carcinogenesis were constructed with 4-nitroquinolone-N-oxide induction. Exhaustion status of T cells was measured by flow cytometry for spleens and by multiplex immunohistochemistry for formalin-fixed paraffin-embedded lesions in multiple stages of oral carcinogenesis. The efficacy of PD-1 blockade with or without cisplatin treatment was evaluated on the mice in precancerous and OSCC stages. We observed higher expression of PD-1 in the human OLK and OSCC tissues compared with the normal, while low expression CTLA-4 in all oral mucosa tissues. Animal experiments showed that the exhausted CD4+ T cells existed much earlier than exhausted CD8+ T cells, and an increased ratio of stem-like exhausted T cells and partially exhausted T cells were detected in the experimental groups. Besides, the expression of immune checkpoint markers (PDCD1, CTLA4 and HAVCR2) was strongly positively correlated with cytokines (IFNG and IL-2). In summary, T-cell exhaustion plays a vital role in oral carcinogenesis, and PD-1 blockade can prevent the progression of oral carcinogenesis.

A 42-year-old man with a history of surgery for tongue cancer was referred to our hospital due to an abnormal chest shadow. High-resolution computed tomography showed lower lobe reticulation. A physical examination revealed nail dystrophy, oral leukoplakia, and reticulated hypopigmentation. Lung biopsy revealed subpleural and perilobular fibrosis, suggestive of usual interstitial pneumonia. However, multiple pathological findings, including homogenous fibrosis and cell infiltration in the centrilobular region, which were compatible with nonspecific interstitial pneumonia, and bronchiolitis were also seen. Genetic testing showed a hemizygous missense mutation in the DKC1 gene, and the patient was diagnosed with dyskeratosis congenita. Although anti-fibrotic therapy was initiated, the patient's respiratory function has continued to decrease.

Made available in DSpace on 2022-05-01T09:30:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-09-01 Background: DNA damage is accumulated in the cells over time as the result of both exogenous and endogenous factors. The objective of this study was to analyze the immunohistochemical expression of the repair proteins in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC). Materials and Methods: Paraffin blocks were selected from the archives of the Laboratory of Hospital Clinico Universitario de Santiago de Compostela, Spain. The sample was composed of 16 cases of OL without dysplasia, 14 cases of OL with dysplasia, and 15 cases of OSCC. The patients' clinical data were collected and immunohistochemical analysis was performed for MLH1, MSH2, MRE11, and XRCC1. The data were submitted to the χ2and the Kruskal-Wallis (P≤0.05) tests. Results: MSH2 was overexpressed in OSCC (P=0.020) and was positive in 100% of patients with OL with dysplasia or OSCC (P=0.019). Positivity for MLH1 was significantly associated with comorbidity (P=0.040), especially in patients who presented with 2 or more pathologies (P=0.028). XRCC1 positivity was also associated with comorbidity (P=0.039). No significant associations were found for the MRE11A expression. Although the simultaneous positivity for the 4 markers was observed in presence of comorbidities (P=0.006). Conclusions: This study supports the effect of the overexpression of MSH2 protein in samples of OL with dysplasia and OSCC, most notably in patients who present with comorbidities and negativity for OL without dysplasia. Oral Medicine Unit Technology Research Center (NPT) Mogi das Cruzes University Mogi das Cruzes, 200 Dr. C ndido Xavier de Almeida Souza Avenue Department of Pathology Clinical Hospital Santiago de Compostela Department of Forensic Sciences and Pathology University of Santiago de Compostela Translational Oncology Laboratory Idichus Foundation Santiago de Compostela School of Medicine Anhembi Morumbi University Department of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (UNESP) Department of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (UNESP)

Objective: Addictions can be beaten if started off with a true motivation to quit it. Enhancing motivation is an important part of overall treatment for smoking cessation as it increases a smoker’s courage and enthusiasm to quit smoke. This study aimed to assess effectiveness of various interventional methods to motivate unmotivated smokers with a focus on changing behavioural stage of smokers to quit. Methodology: A single blinded trial was conducted at the outpatient department of ITS dental college and hospital among precontemplation stage smokers allocated into 4 groups and given interventional therapies like general counselling only(group 1), counselling and intra oral camera assessment (Group 2), counselling as well as carbon monoxide monitoring(Group 3)whereas fourth group(Group 4) given a combination therapy of all of them. A baseline evaluation of nicotine dependence and behavioural stage of the smoker was assessed. The patients were then evaluated on presence on their scheduled follow up visits done at interval of 2 weeks and 4 weeks. Descriptive statistics were addressed and the association was evaluated using Pearson chi square test. Any p value less than 0.05 was considered statistically significant. Results: Majority of smokers were males(88% ) and about 48.8% of them were highly dependent smokers . The change in precontemplation behavioural stage was assessed on basis of follow up visits after interventional therapy which was significantly higher in group 4 receiving combination therapy, followed by carbon monoxide therapy ,counselling and intra oral camera assessment and the least visits in behaviour counselling group (p

Proliferative verrucous leukoplakia (PVL) is a rare and refractory form of oral mucosal leukoplakia of unknown origin, characterized by high rates of malignant transformation. Different diagnostic criteria, terminologies, and therapeutic approaches have been proposed since the first report in 1985. There remains no general agreement regarding the clinical and histological diagnosis, prevention, and correct management of this disease. This retrospective study investigated 48 patients affected by PVL showing at least one malignant transformation and followed up at 2-month intervals. Twenty-five were female (52.1%) and 23 (47.9%) were male; their median age was 67 years (range 40-93 years). Follow-up ranged from 18 to 240 months. Clinical examination included the use of Lugol's solution to prevent clinical underestimation of the margins and toluidine blue for suspicious areas. Surgical excision by scalpel was the preferred treatment for suspicious lesions, with only five carcinomas surgically removed by diode laser and two by CO2 laser. All specimens were accurately mapped after formalin fixation. Fifteen patients (31.3%; 10 female, five male) developed one oral carcinoma, while 33 (68.7%) developed two or more primary tumours (range 3-12). Only four patients (8.3%), who developed between 2 and 8 oral squamous cell carcinomas (OSCCs), died of tumour-related causes. The pre-surgical clinical workup, subsequent surgical treatment, and follow-up are key to success for patients affected by PVL with malignant transformation into stage 1 OSCC and/or verrucous carcinoma, leading to a high overall survival rate.

Background The tongue has been identified as a high-risk site for malignant transformation of oral leukoplakia. The purpose of this study was to investigate the clinicopathological characteristics and treatment outcomes of the dorsal and ventrolateral tongue leukoplakia. Methods Demographic data and pathological results of patients who underwent carbon dioxide laser surgery for tongue leukoplakia from 2002 to 2019 were retrospectively reviewed and analyzed statistically. Results Of the 111 patients enrolled, 80 were males and 31 females, with a mean age of 51.86 ± 11.84 years. The follow-up time was 3.74 ± 4.19 years. Fifteen patients had a postoperative recurrence (13.51%). Four (3.6%) patients developed malignant transformation. Annual transformation rate was 1.08%. There were no differences in the time to develop carcinoma (3.19 ± 1.94 vs. 3.51 ± 2.12 years, P = 0.83), overall cumulative malignant transformation rates (7.41% vs. 2.25%, P = 0.12), and annual transformation rates (2.32% vs. 0.64%, P = 0.099). The prevalence of the ventrolateral tongue leukoplakia was higher than that of the dorsal tongue leukoplakia (P P = 0.045). Conclusions Dorsal tongue leukoplakia is not as frequently encountered clinically as ventrolateral tongue leukoplakia. The response of the dorsal tongue and ventrolateral tongue leukoplakia to laser therapy of are comparable in postoperative recurrence and postoperative malignant transformation. Clinicians should take a more aggressive attitude toward oral tongue leukoplakia with higher grade of dysplasia.

Background The doctor/nurse and police officer population have some common typical characteristics of great professional pressure and night shift and past studies indicated oral mucosa lesions were closely associated with psychological factors and health-risking behaviors, however the prevalence of recurrent aphthous stomatitis (RAS) and the two commonly seen oral potentially malignant disorders of oral submucosal fibrosis (OSF) and oral leukoplakia in doctor/nurse and police officer in the Betel quid chewing city of Mainland China is unknown The cross-sectional study was to determine the prevalence differences of RAS, oral leukoplakia and OSF among doctor/nurse, police officer and non-doctor/nurse and non-police officer population aged 20–59 years. Methods RAS, OSF and oral leukoplakia were examined in doctor/nurse group (male: 659, female: 2439), police officer group (male: 839, female: 262) and non-doctor/nurse and non-police officer group (male: 7576, female: 8129) from 2020-11-01 to 2021-08-31 in Health Management Center, Xiangya Hospital in Changsha city, Hunan province. Results The prevalence rates of RAS, OSF, oral leukoplakia and oral leukoplakia combined with OSF in male and female non-doctor/nurse and non-police officer group are 8.32‰ and 10.83‰, 58.08‰ and 1.23‰, 11.75‰ and 0.25‰, 7.66‰ and 0.12‰ respectively. Compared with the non-doctor/nurse and non-police officer population, prevalence rates of RAS in male (24.27‰) and female (20.50‰) doctor/nurse population were significantly higher. Prevalence rates of OSF (21.24‰) and oral leukoplakia (3.03‰) in male doctor/nurse population were significantly less but prevalence rates of OSF (93.71‰), oral leukoplakia (20.17‰) and oral leukoplakia combined with OSF (15.42‰) for male police officer were significantly greater in comparison with male non-doctor/nurse and non-police officer group. OSF and oral leukoplakia prevalence rates were obvious lower for the female than the counterpart male group, but there were no significant differences of OSF and oral leukoplakia prevalence rates between the female non-doctor/nurse and non-police officer and female doctor/nurse group. Oral leukoplakia was not found in the female police officers. Conclusions Doctor/nurse population have higher prevalence of RAS. Male doctors/nurses have lower prevalence of OSF and oral leukoplakia, while male police officers have higher prevalence of OSF, oral leukoplakia and oral leukoplakia combined with OSF.

Background To investigate oral leukoplakia (OL) and risk of upper gastrointestinal (UGI) cancer deaths in the Linxian Dysplasia Nutrition Intervention Trial (NIT) cohort. Methods A total of 3318 subjects with esophageal squamous dysplasia enrolled on 1 May 1985, and were followed up until 30 September 2015. Participants with OL at baseline were treated as an exposed group, while the remainder was selected as a control group. All subjects were followed monthly and reviewed quarterly by the Linxian Cancer Registry. Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results During the 30‐year follow‐up, a total of 902 UGI cancer deaths occurred, including 541 esophageal squamous cell carcinoma (ESCC) related, 284 gastric cardia carcinoma (GCC) related, and 77 gastric noncardia carcinoma (GNCC) related deaths. Relative to subjects without OL, the long‐term risk of ESCC mortality in participants with OL increased by 26.1% (HR = 1.26, 95% CI: 1.05–1.52). In the subgroup analyses, adverse effects of OL on ESCC mortality were observed especially in younger subjects (HR = 1.48, 95% CI: 1.11–1.97), females (HR = 1.44, 95% CI: 1.11–1.89), non‐smokers (HR = 1.44, 95% CI: 1.15–1.81), nondrinkers (HR = 1.28, 95% CI: 1.04–1.57), and individuals with a family history of cancer (HR = 1.37, 95% CI: 1.05–1.79). No associations were observed between OL and risk of GCC and GNCC mortality. Conclusions OL may increase the long‐term risk of ESCC mortality, especially in younger subjects, females, nondrinkers, non‐smokers, and subjects with a family cancer history. Future studies are needed to explore the potentially etiological mechanism., OL could increase the long‐term risk of ESCC mortality, especially in younger subjects, females, nondrinkers, non‐smokers, and subjects with a family cancer history. The specific etiological mechanism needs to be further explored.

Objective: Oral cancer usually has an early precancerous stage before its actual malignant transformation. Although there are various approaches to diagnose early stages of cancer, yet there is one less explored, cost effective and simple technique known as crystallization test. The aim of the study was to reaffirm the effectiveness of Pfeiffer’s crystallization test in screening oral leukoplakia and squamous cell carcinoma. Methods: Fifty oral leukoplakia, sixty five oral squamous cell carcinoma and sixty healthy individuals participated in crystallization test. Single blood drop was used to perform the test and obtained crystal patterns were analysed. Cross tabulation and Chi-Square test was performed to find the frequency and association between the groups. Kruskal-Wallis H test and Mann Whitney U test was applied comparing mean transverse form. Results: Sensitivity of crystallization test was 80% and 93.84% in oral leukoplakia and squamous cell carcinoma. Chi-Square analysis revealed highly significant transverse form between the study groups (p < 0.000). Conclusion: Crystallization test proves to be simple, reliable and minimal invasive diagnostic approach under strictly maintained physical conditions.

Oral leukoplakia is the most common oral potentially malignant disorder with a malignant transformation rate into oral squamous cell carcinoma of 1–3% annually. The presence and grade of World Health Organization defined dysplasia is an important histological marker to assess the risk for malignant transformation, but is not sufficiently accurate to personalize treatment and surveillance. Differentiated dysplasia, known from differentiated vulvar intraepithelial neoplasia, is hitherto not used in oral dysplasia grading. We hypothesized that assessing differentiated dysplasia besides World Health Organization defined (classic) dysplasia will improve risk assessment of malignant transformation of oral leukoplakia. We investigated a retrospective cohort consisting of 84 oral leukoplakia patients. Biopsies were assessed for dysplasia presence and grade, and the expression of keratins 13 (CK13) and 17, known to be dysregulated in dysplastic vulvar mucosa. In dysplastic oral lesions, differentiated dysplasia is as common as classic dysplasia. In 25 out of 84 (30%) patients, squamous cell carcinoma of the upper aerodigestive tract developed during follow-up. Considering only classic dysplasia, 11 out of 56 (20%) patients with nondysplastic lesions progressed. With the incorporation of differentiated dysplasia, only 2 out of 30 (7%) patients with nondysplastic lesions progressed. The risk of progression increased from 3.26 (Hazard ratio, p = 0.002) when only classic dysplasia is considered to 7.43 (Hazard ratio, p = 0.001) when classic and differentiated dysplasia are combined. Loss of CK13, combined with presence of dysplasia, is associated with greater risk of malignant progression (p = 0.006). This study demonstrates that differentiated dysplasia should be recognized as a separate type of dysplasia in the oral mucosa and that its distinction from classic dysplasia is of pathological and clinical significance since it is a strong (co)prognostic histopathological marker for oral malignant transformation. In oral lesions without dysplasia and retained CK13 staining the risk for progression is very low.

The objective of this study was to review the diagnostic accuracy of clinicians identifying leukoplakia and the diagnostic terminology used to indicate leukoplakic lesions at the University of Nebraska Medical Center (UNMC) oral biopsy service. Biopsy archives from the years 1983, 1995, 2005, and 2015 in the UNMC College of Dentistry were reviewed. Cases with a clinical diagnosis of leukoplakia (or white plaque), hyperkeratosis, dysplasia, and/or carcinoma were included in the study. Demographic and clinical information was recorded and descriptive statistics were utilized. Of 6113 cases, 517 lesions (8.46%) from 508 patients met the inclusion criteria. The mean age of the patients was 56.87 years, and the sample included 286 men and 222 women. Of these 517 lesions, 195 (37.72%) were clinically diagnosed as leukoplakia or white plaque. The records revealed that 133 (68.21%) of 195 clinical diagnoses were correct, with lesions histologically exhibiting hyperkeratosis (75 cases), dysplasia (52 cases), or carcinoma (6 cases). The remaining 62 lesions (31.79%) were found to have other histologic diagnoses. Hyperkeratosis made up the largest portion of the correct diagnoses. In general, the ability of clinicians to successfully identify leukoplakia improved over the years (46.15%, 73.68%, 64.29%, and 76.00% in 1983, 1995, 2005, and 2015, respectively). However, clinicians continue to misclassify identifiable pathoses such as lichen planus, lichenoid mucositis, and fibroma as leukoplakia. Hyperkeratosis and dysplasia, both of which represent histologic diagnoses, appear to be popularly misused clinical terms.

PVL (proliferative verrucous leukoplakia) has distinct clinical characteristics. They have a proclivity for multifocality, a high recurrence rate after treatment, and malignant transformation, and they can progress to verrucous or squamous cell carcinoma. AI can aid in the diagnosis and prognosis of cancers and other diseases. Computational algorithms can spot tissue changes that a pathologist might overlook. This method is only used in a few studies to diagnose LB and PVL. To see if their cellular nuclei differed and if this cellular compartment could classify them, researchers used a computational system and a polynomial classifier to compare OLs and PVLs. 161 OL and 3 PVL specimens in the lab were grown, photographed, and used for training and computation. Exam orders revealed patients’ sociodemographics and clinical pathologies. The nucleus was segmented using Mask R-CNN, and LB and PVL were classified using a polynomial classifier based on nucleus area, perimeter, eccentricity, orientation, solidity, entropies, and Moran Index (a measure of disorderliness). The majority of OL patients were male smokers; most PVL patients were female, with a third having malignant transformation. The neural network correctly identified cell nuclei 92.95% of the time. Except for solidity, 11 of the 13 nuclear characteristics compared between the PVL and the LB showed significant differences. The 97.6% under the curve of the polynomial classifier was used to classify the two lesions. These results demonstrate that computational methods can aid in diagnosing these two lesions.

Objective Accumulating evidence suggests that macrophages are involved in the immunoediting of oral squamous cell carcinoma but the role of macrophages in oral carcinogenesis is unclear. We aimed to clarify the role of macrophages in oral leukoplakia, which is the most common oral potentially malignant disorder from immunotolerance viewpoint. Materials and methods The study included 24 patients who underwent surgical resection for tongue leukoplakia. The relationships between macrophage markers and clinicopathological factors were assessed. Conditioned medium was harvested from the CD163(+) human monocytic leukaemia cell line, THP-1. The phenotypic alteration of human oral keratinocytes by the conditioned medium treatment was assessed using quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Moreover, the clinical samples were evaluated using immunohistochemistry. Results Tongue leukoplakia tissues with high CD163(+) macrophage infiltration were associated with significantly higher degrees of epithelial dysplasia, abnormal Ki-67 expression and cytokeratin13 loss when compared with the tissues with low CD163(+) macrophage infiltration. In vitro, CD163(+) THP-1 conditioned medium induced immunosuppressive molecules, especially interleukin-10 (IL-10) in human oral keratinocytes. The IL-10 expression levels showed significant positive correlations with not only the numbers of FOXP3(+) regulatory T cells but also that of CD163(+) macrophages. Conclusions In tongue leukoplakia, CD163(+) macrophages infiltration correlates with immunosuppressive cytokine IL-10 expression.

Objectives To analyse the clinical and histopathological features of oral leukoplakia (OL) in the Sudan, and to identify the risk factors associated with dysplastic and malignant changes. Methods Records of 117 cases with the diagnosis of OL at the Department of Oral Pathology in the period from 2010 to 2017 were reviewed. Results Of the 117 cases included in this study, 30 cases (25.6%) showed carcinoma in the initial diagnostic biopsy. The mean age at diagnosis was 59.8 years with a male/female ratio of 3.3:1. The lip (48.7%) and the gingiva (31.6%) were the predominantly affected sites. Multivariate regression analysis revealed that females were associated with 3.36-fold [95% confidence interval (CI), 1.36-10.76; P = 0.012] higher risk of malignant transformation compared with males. Verrucous leukoplakia was associated with 3.38-fold (95% CI, 1.12-10.19; P = 0.031) higher risk of malignant transformation compared with homogeneous leukoplakia. Exclusive Toombak dipping was the significant risk factor for the presence of dysplasia in OL (odds ratio, 9.35; 95% CI, 1.28-67.99; P = 0.027). Conclusions Clinical and histopathological features of OL were analysed and correlated. Toombak dipping was the significant risk factor for dysplastic changes, while female gender and verrucous leukoplakia were the factors associated with malignant transformation.

The aim of this multicenter retrospective study is to characterize the histopathologic features of initial/early biopsies of proliferative leukoplakia (PL; also known as proliferative verrucous leukoplakia), and to analyze the correlation between histopathologic features and malignant transformation (MT). Patients with a clinical diagnosis of PL who have at least one biopsy and one follow-up visit were included in this study. Initial/early biopsy specimens were reviewed. The biopsies were evaluated for the presence of squamous cell carcinoma (SCCa), oral epithelial dysplasia (OED), and atypical verrucous hyperplasia (AVH). Cases that lacked unequivocal features of dysplasia were termed "hyperkeratosis/parakeratosis not reactive (HkNR)". Pearson chi-square test and Wilcoxon test were used for statistical analysis. There were 86 early/initial biopsies from 59 patients; 74.6% were females. Most of the cases had a smooth/homogenous (34.8%) or fissured appearance (32.6%), and only 13.0% had a verrucous appearance. The most common biopsy site was the gingiva/alveolar mucosa (40.8%) and buccal mucosa (25.0%). The most common histologic diagnosis was OED (53.5%) followed by HkNR (31.4%). Of note, two-thirds of HkNR cases showed only hyperkeratosis and epithelial atrophy. A lymphocytic band was seen in 34.8% of OED cases and 29.6% of HkNR cases, mostly associated with epithelial atrophy. Twenty-eight patients (47.5%) developed carcinoma and 28.9% of early/initial biopsy sites underwent MT. The mortality rate was 11.9%. Our findings show that one-third of cases of PL do not show OED with most exhibiting hyperkeratosis and epithelial atrophy, but MT nevertheless occurred at such sites in 3.7% of cases.

Purpose Oral cancers lack standardized monitoring systems. Our institution has developed an active surveillance system which provides detailed monitoring and follow up of patients with oral preneoplastic lesions (OPL). We examined a historic cohort of patients with OPL seen by regional dental professionals and a current cohort of clinic patients. The major aim was to examine follow up practices for biopsy proven dysplasia to gauge appropriateness of an active monitoring system for oral carcinoma. Materials and methods Questionnaires regarding patients with OPL were sent to 285 dentists who had requested oral pathology services from our institution. The follow up practices of 141 dentists were evaluated for patients with OPL. We then examined our current clinic referral patterns for the number of dental referrals after the creation of an oral carcinoma active surveillance clinic. Results There were 76.5% (108/141) of patients who received follow up after diagnosis of preneoplastic oral lesions with 14.1% who underwent repeat biopsy. There was a malignant transformation rate of 11.3% including transformation of 42.8% of severe dysplasias into carcinoma within 2 years. After establishment of a dental referral clinic, 21.8% of tumor visits in a six-week period were referred from the regional dental community. Conclusions A high rate of transformation of OPL to cancer in this cohort may support a role for joint dental and otolaryngology surveillance of dysplasia with longitudinal follow up.

Leukoplakia is common with a 1 % incidence in the population and may harbor preneoplastic changes. Diode lasers provide both precision and coagulation for excision of superficial lesions in clinical and operative settings with little damage to deeper tissue. We aim to determine the rate of oral and oropharyngeal hyperkeratosis and dysplasia recurrence after treatment with diode laser.Patients with oral or oropharyngeal hyperkeratotic or mild dysplastic lesions treated with pulsed diode laser between 2013 and 2020 at a tertiary academic institution were analyzed. The main outcome measure was recurrence of hyperkeratosis and dysplasia after treatment.Fourteen patients received diode laser treatment for hyperkeratotic or mild dysplastic lesions of the oral cavity or oropharynx. Demographic features included 9 (64.3 %) females and mean age of 66.6 years. In these 14 patients, 18 distinct lesions were identified. Eleven (61.1 %) lesions were located on the oral tongue, 4 (22.2 %) on the buccal mucosa, 2 (11.1 %) on the hard palate, and 1 (5.6 %) on the soft palate. Average time from lesion clinical diagnosis to the first diode laser treatment was 8.3 months with an average number of 1.4 treatments per lesion. Three (16.7 %) lesions experienced recurrence after the most recent treatment. None of the lesions underwent malignant transformation. None of the patients experienced bleeding, tethering, or dysarthria after treatment. One patient developed pyogenic granuloma and reported chronic tongue pain.Pulsed diode laser treatment of leukoplakia was well tolerated with low complication rates and reasonable control of precancerous lesions.

Oral verruciform hyperkeratotic lesions (OVHLs) affecting the gingiva and palate are frequent in proliferative verrucous leukoplakia (PVL). Intraoral hyperkeratotic lesions can also be observed in epidermolytic keratodermas, albeit such association has received limited attention in oral and maxillofacial pathology. The authors report on 5 individuals whose plantar (PK) or palmoplantar keratodermas (PPKs) were confirmed after evaluation of gingival leukoplakic biopsies.Two women and 3 men, ages 18 to 64, presented with solitary or diffuse leukoplakias of the attached gingiva and hard palate, clinically interpreted as PVL. All individuals underwent diagnostic gingival and/or palatal biopsies.Microscopically, the lesions featured verruciform hyperparakeratosis, occasionally conspicuous hypergranulosis and acanthosis. In the spinous cell layer, numerous cells presented with vacuolated cytoplasm and paranuclear eosinophilic condensations that, infrequently, engulfed the nucleus. The histopathologic findings were interpreted as verrucous hyperkeratosis consistent with those described in epidermolytic PPKs. Further evaluation of the individuals for cutaneous lesions disclosed PK or PPKs in all 5 patients. Additionally, the men exhibited elbow and subungual hyperkeratoses. A family history of keratodermas was confirmed in all 3 male individuals.Gingival and/or palatal OVHLs associated with PK and PPKs display pathognomonic histopathologic features and exhibit indolent biologic behavior. Therefore, any confusion with PVL should be avoided to prevent overtreatment.

Background: The aim of this study was to make a comparison of clinicopathological characteristics of oral leukoplakia between male and female patients following carbon dioxide laser excision for oral leukoplakia and analyze the factors associated with the treatment outcomes in female patients. Methods: Medical records of patients with oral leukoplakia receiving laser surgery from 2002 to 2020 were retrospectively reviewed and analyzed statistically. Results: A total of 485 patients were enrolled, including 412 male (84.95%) and 73 female (15.05%). Regarding the locations, the predilection site of oral leukoplakia in male patients was buccal mucosa (p = 0.0001) and that for women patients was tongue (p = 0.033). The differences of recurrence and malignant transformation between both sexes were not significant (p &gt, 0.05). Among female patients, area of oral leukoplakia was the risk factor related to recurrence (p &lt, 0.05). Clinical morphology and postoperative recurrence were the risk factors related to malignant transformation (p &lt, 0.05). Conclusions: In comparison with male patients, there was no significant difference of the postoperative recurrence and malignant transformation of oral leukoplakia in female patients. Among the female patients, clinicians should pay more attention to large-sized and non-homogeneous leukoplakia, and postoperative recurrent lesions.

BACKGROUND Proliferative verrucous/multifocal leukoplakia (PVML) is an oral potentially malignant disorder (OPMD) that exhibits high rates of malignant development (MD). This study aimed to analyse the risk of MD of PVML, as well as to investigate the possible risk factors associated with its malignization. METHODS A bibliographical search of the PubMed, Embase, Web of Science, and Scopus databases was conducted. PVML MD rates were calculated as a pooled proportion, and the risk factors were calculated as risk ratios, using fixed and random models based on the presence of heterogeneity. RESULTS From a total of 417 records, 16 articles were retrieved for inclusion. The subgroup analysis revealed a higher MD rate in the studies that were conducted in America, and, likewise, said studies involved a longer follow-up time (>6 years). There was a non-significant lower risk of malignization among males. A negative correlation was observed between MD and the year in which the studies were published. CONCLUSIONS The pooled MD of PVML was 65.8% (95% CI: 55.3-76.2, p

The immune evasion of dysplastic cells plays an important role in suppressing the immune response and progression of malignancy. The role of the complement inhibitors in the development of oral epithelial dysplastic lesions and squamous cell carcinoma (SCC) is still unclear.This study aimed to assess the expression of C4 binding protein (C4BP) as a complement inhibitor in oral squamous cell carcinoma and leukoplakia.In this study, 94 samples were classified into four groups: leukoplakia with mild to moderate dysplasia, leukoplakia with severe dysplasia or carcinoma in situ, early invasive SCC, and invasive SCC. The expression of C4BP marker was evaluated by immunohistochemistry (IHC) and real-time PCR. The results were analyzed by the Kruskal-Wallis, Bonferroni adjusted Dunn's multiple comparison, and one-way ANOVA tests.The results of IHC revealed the expression patterns of C4BP in oral dysplasia and SCC, and indicated that the C4BP expression was not significantly different between different histopathological grades in epithelial cells and vessels (P=0.157 and P=0.123, respectively) but, it was significantly different in fibroblasts and lymphocytes (P=0.017 and P=0.043, respectively). The real-time PCR showed a significant correlation between the dysplasia grade and expression of C4BP (P0.05).According to the results, C4BP is expressed in the cancerous tissue by the tumor cells and their surrounding stroma. In addition, upregulation of the C4BP gene as an inhibitor of the complement system is a possible strategy adopted by the tumor cells to evade the immune system.

Background/Purpose: Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) may be present in oral mucosal disease patients. This study mainly assessed the frequencies of serum GPCA, TGA, and TMA positivities in 131 oral precancer patients. Methods: Serum GPCA, TGA, and TMA levels were measured in 131 oral precancer patients including 96 oral leukoplakia, 26 oral erythroleukoplakia, and 9 oral verrucous hyperplasia patients and in 131 age- and sex-matched healthy control subjects. Results: We found that 131 oral precancer patients had higher frequencies of serum GPCA (10.7% vs. 2.3%, P = 0.012, statistically significant), TGA (4.6% vs. 2.3%, P = 0.498), and TMA (8.4% vs. 2.3%, P = 0.054, marginal significance) positivities than 131 healthy control subjects. We also found that 1 (0.8%), 6 (4.6%), and 16 (12.2%) oral precancer patients had the presence of three (GPCA + TGA + TMA), two (GPCA + TGA, GPCA + TMA, or TGA + TMA), or one (GPCA only, TGA only, or TMA only) autoantibody in their sera, respectively. Of 10 TGA/TMA-positive oral precancer patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 80%, 10%, and 10% of these 10 TGA/TMA-positive oral precancer patients had normal, lower, and higher serum TSH levels, respectively. We also found a significantly higher GPCA positive rate in 26 smokers consuming >20 cigarettes per day than in 61 smokers consuming ≤20 cigarettes per day (P = 0.008). Conclusion: Approximately 17.6% of 131 oral precancer patients have serum GPCA/TGA/TMA positivity. Only approximately 20% of TGA/TMA-positive oral precancer patients have either hypothyroidism or hyperthyroidism. Keywords: Oral leukoplakia, Oral precancer, Gastric parietal cell antibody, Thyroglobulin antibody, Thyroid microsomal antibody

PIWIL2 is a human Argonaute protein, which is guided by small RNAs to its targets, plays a role in germ cell maintenance and has been proposed to be expressed in precancerous stem cells and tumor stem cells. However, the significance of PIWIL2 expression in oral cancer and precancerous lesions has not been investigated. In this study, we analyzed the expression of the stem cell protein PIWIL2 in oral squamous-cell carcinoma (OSCC) and in premalignant oral leukoplakia (OL) with predominant expression in malignant and premalignant tissues. In the evaluated patients, we found that PIWIL2 was associated significantly with OSCC prognosis and OL. Furthermore, PIWIL2 was found to be expressed in tumor epithelial cells and macrophages in the tumor microenvironment, which are not derived from enlarged lymph nodes. Cytological experiments confirmed that the human squamous cell carcinoma cell line SCC-25, can promote the PIWIL2 and Nanog level in THP-1 cells, which are extensively used to study the modulation of monocytes and macrophages. Our findings showed that PIWIL2 can predict effectively OSCC prognosis and OL with a high risk of OSCC development and substantiate the deduction that cancer stem(-like) cells in oral cancer have the ability to reconstitute the heterogeneity of the bulk tumor and contribute to poor outcome and immunosuppression.

Objective: This study aims to investigate the expression changes of periostin (PN or OSF-2) in oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC), and analyze its significance ...

Objectives To map the genomic pathways of patients with oral leukoplakia (OLK) which transformed to cancer (progressive) and those which did not (non-progressive), and to compare their exomic profiles. Materials and methods Whole exome sequencing was performed on 42 sequential samples from five progressive and eight non-progressive patients. Association of genomic variant frequencies with progression or lesion severity were analysed by non-parametric tests (Kruskal-Wallis and Mann-Whitney-Wilcoxon) and multivariate sparse partial least squares discriminant analysis (sPLS-DA). Enrichment analysis was used to characterise the effect of mutations upon biological pathways. Confirmatory studies used qPCR and immunohistochemistry. Results Using sPLS-DA, the variant frequency of a small number of genes could be used to classify the samples based on lesion severity or progressive status. Enrichment analysis showed that DNA damage repair gene related pathways were highly impacted in lesions which progressed to cancer. Multivariate analysis of a set of 148 DNA damage repair genes could be used to classify progressive lesions using mutation frequency. BRCA1, BRCA 2 and other double strand break (DSB) repair Fanconi anaemia (FA)/BRCA pathway genes were prominent contributors to this classification. Conclusion Patients with progressive and non-progressive OLK can be differentiated using the frequency of exomic variants, particularly in DNA damage repair pathway genes. To our knowledge, this is the first report of FA/BRCA (DSB) pathway involvement in malignant transformation of OLK to oral squamous cell carcinoma (OSCC).

To describe the number of second primary malignancies in a series of 33 patients with proliferative verrucous leukoplakia (PVL), detailing the mean time between primary malignancies and their clinical characteristics. Two groups of patients were included in this study: group 1 comprised 33 PVL patients who had developed ≥ 2 oral squamous cell carcinoma (OSCC) and group 2 comprised 48 PVL patients without malignant degeneration. We compared the groups with regard to age, gender, oral location, and number of oral sites affected. For patients in group 1, we determined the locations, clinical forms, and TNM stages of oral cancers. We also recorded the intervals of time between instances of oral cancer for all patients. The groups did not differ significantly in age; however, group 1 included more women (p

ObjectiveOral leukoplakia is keratinized lesions in the buccal mucosa, tongue, and gingiva. It is the most common oral precancerous lesion; oxidative stresses and irrelevant autophagy have been reported to be the cause of oncogenesis. p62, a cytoplasmic protein induced by oxidative stress, is an adaptor protein involved in the formation of protein aggregates and induction and inhibition of autophagy. The inhibition of autophagy induces p62 overexpression and promotes oncogenesis via the oncogenic signaling pathway. The aim of the present study was to elucidate the involvement of intracellular expression of p62 in oral leukoplakia and to address its potential clinical implementation as a biomarker to predict malignant transformation.Material and MethodsFifty samples from subjects with confirmed oral leukoplakia were evaluated by immunohistochemical staining for the expression of p62, 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), Ki67, and p53. Univariate and multivariate logistic regression analyses were performed to evaluate the association between p62, 8‐OHdG, Ki67, and p53 and clinical characteristics, including epithelial dysplasia.ResultsSignificant associations were observed between p62 expression in the nucleus, p62 aggregation, and epithelial dysplasia (adjusted odds ratio [OR] = 5.75; 95% confidence interval [CI]: [1.28, 26.2]; .024 and OR = 6.16; 95% CI: [1.01, 37.4]; .048, respectively). The expression of p62 in the cytoplasm and the levels of 8‐OHdG, Ki67, and p53 were not significantly associated with epithelial dysplasia. A significant relationship was found between p62 expression in the nucleus and p53 expression (OR = 3.94; 95% CI: [1.14, 13.6]; .031).ConclusionsThe results suggested that p62 expression in the nucleus and p62 aggregation can be potential markers to predict the malignant transformation of oral leukoplakia.

Oral potentially malignant disorders (OPMD) may develop malignant characteristics and transform into oral squamous cell carcinoma (OSCC) in a range of 1% to 2% of cases. Chronic alcohol consumption is associated with carcinogenesis, but its mechanism has not yet been fully elucidated. ALDH1A1 and 2, isoenzymes responsible for aldehyde oxidation involved in ethanol metabolism may be associated with the development of malignant head and neck neoplasms. The aim of this study was to analyze the expression of ALDH1A1 and ALDH2 in oral leukoplakia with epithelial dysplasia (OLP) and OSCC. A retrospective study was conducted on 27 cases of OLP and 30 cases of OSCC. Clinical data were obtained from medical records, and all cases were classified as mild, moderate, and severe for OLP, and well-differentiated, moderately differentiated, or poorly differentiated for OSCC cases. The ALDH1A1 and ALDH2 expression in OLP and OSCC was evaluated by the immunohistochemical technique. There was predominance of the male sex, in both OLP and OSCC cases. Oral tongue was the most affected site in both groups. OLP showed positive protein expression of ALDH1A1 in all cases, both basal and suprabasal epithelial layers, whereas ALDH2 showed less protein expression. In OSCC, the immunohistochemical reaction for ALDH1A1 expression was negative in 70%, whereas ALDH2 expression was positive in all cases. This study demonstrated the gradual loss of ALDH1A1 expression in OSCC in comparison with OLP, and the increased ALDH2 expression in OSCC.

Objective The molecular mechanisms underlying the development of dysplasia in leukoplakia are unknown. We used RNA sequencing to examine the molecular and biological pathway differences in oral leukoplakia with and without oral epithelial dysplasia. Materials and methods Excisional biopsy specimens (25) were taken from 24 patients with oral leukoplakia diagnosed histopathologically as either oral epithelial dysplasia (13) or epithelial hyperplasia and keratosis without dysplasia (12). Transcriptome analysis used RNA sequencing, differential expression and hierarchical clustering. Biological signalling was examined by gene ontology, pathway and protein-protein interaction analysis. Results Differential expression analysis showed distinction between the two groups identifying 47 genes as altered in leukoplakia with dysplasia, including SAA1, SAA2, KRT31, KRT37, KRT76, ROBO2, DNAJB5 and DNAJA4. Using hierarchical clustering, dysplastic leukoplakia readily segregated from leukoplakia without dysplasia. Pathway and ontology enrichment analysis provided evidence that downregulation of extracellular matrix (ECM) pathways was a feature of dysplastic lesions. Conclusion Our results suggest that there are detectable changes in the molecular profile of oral leukoplakia exhibiting dysplasia including downregulated ECM as a distinguishing feature of dysplastic lesions. This suggests that reactive changes in stroma may be an early manifestation of dysplastic development. Our study also demonstrates the feasibility of detecting such molecular changes in oral leukoplakia, providing avenues for further investigation of molecular mechanisms of oral dysplasia.

Objective: The aim of this study was to compare the efficacy of Er:YAG and Er, Cr:YSGG laser in the treatment of oral leukoplakia refractory to conventional retinoid therapy. Materials and methods: The study sample consisted of 54 patients (16 men and 38 women) who were histopathologically diagnosed with oral leukoplakia that was refractory to conventional retinoid therapy. Patients were randomly allocated into two groups according to the type of the laser used for treatment of oral leukoplakia: Group 1. Er:YAG laser ; Group 2. Er, Cr:YSGG laser. Patients were recalled at 6 months and 1 year after treatment to evaluate possible recurrence and assess the patients’ postoperative quality of life. Results: After initial ablation, the degree of residual lesion was significantly greater in the Er:YAG laser group (74.1%), compared with the Er, Cr:YSGG group (18.5%) (p=0.0001). Six months and 1 year after the second ablation, there was no lesion recurrence in either laser group. Fourteen days after the initial ablation, the visual analog scale (VAS) pain rating and the total oral health impact profile score fell significantly in both groups (p

Purpose Oral leukoplakia (OL) is the well-known disorder of oral mucosa, which has potential to be malignant and can lead to squamous cell carcinoma (OSCC). In the following study, we developed a comprehensive nomogram for predicting the malignant progression of OL, based on analysis of clinicopathological variables. Methods A retrospective analysis of patients diagnosed with OL was performed between 1998 and 2017 at the Peking University School and Hospital of Stomatology. OL was confirmed by pre-treatment biopsy. The candidate risk factors for OL malignant transformation were screened from clinicopathological variables using the Cox proportional hazard regression analysis. The nomogram model was generated based on the COX regression results and was validated through Harrell concordance index (c-index) and calibration plots RESULTS: The incidence of OL malignant transformation (MT) was 12.2% (107/875), and the mean follow-up time was 4.5 years. The risk factors (age, histologic grade, site of lesion and smoking habit) derived from Cox proportional hazard regression analysis were incorporated in a novel nomogram model for prediction of MT severity. The c-index value of the nomogram model was 0.752, which confirmed the prediction ability; and was further confirmed by calibration plots results. Conclusion Our data suggest that patients with OL who are over 50 years old, non-smokers with dysplasia, and OL lesions involving the lip, the floor of mouth, and tongue have an enhanced risk of MT. The established nomogram model has the predictive value of malignant progression, which is conductive to screen high-risk patients and guide treatment strategy.

Purpose The aim of this prospective work was to examine oral leukoplakia for their podoplanin expression to determine whether podoplanin expression is associated with the degree of dysplasia. Materials and methods We took biopsy samples from 50 patients with oral leukoplakia in 2013. The preparations studied by immunohistochemistry were analyzed in correlation with the degree of dysplasia and other clinicopathological variables. Results The Chi-square test showed a significant correlation between podoplanin expression and the degree of dysplasia according to the squamous intraepithelial neoplasia (SIN) classification (p = 0.033). Also, a significant association between age grouping and podoplanin expression was found. We were able to show that the distribution is the same for both age groups in relation to the score of podoplanin expression (p = 0.003). Conclusion In a comparable retrospective work of our working group, it could be shown that podoplanin is a reliable predictive marker for the assessment of the risk of malignant transformation. The present work was able to substantiate the assumption that podoplanin not only plays an important role in the context of malignant degeneration but also exerts a major influence in advance.

Background Oral leukoplakia (OL) is a potentially malignant oral mucosal disorder. A casual association between OL, oral squamous cell carcinoma (OSCC) and human papillomavirus (HPV) infection has been suggested, but no conclusive evidence has been presented. p16, a tumour-suppressor protein, is used as a surrogate marker for HPV infection. The aim of this study was to investigate how overexpression of p16 correlates with HPV infection in OL and in OSCC. Patients and methods Seventy-four patients with OL and 13 with OSCC with p16 overexpressed, were analyzed by immunohistochemistry visualizing p16 and a real-time polymerase chain reaction (PCR) assay targeting HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 52, 56, 58 and 59. Results Overexpression of p16 was observed in 18% of patients with OL. None of the HPV subtypes were detected by PCR analysis in patients with OL. In the p16-positive OSCC specimens, 38% were also HPV16-positive. Conclusion Overexpression of p16 was not found to be a reliable biomarker for HPV infection in patients with OL and OSCC.

BACKGROUND The associations between malignant transformation of oral potentially malignant disorders (OPMDs), oral cancer development and prognosis, and apurinic/apyrimidinic endonuclease 1 (APE1) functional polymorphisms are unclear. METHODS Patients with OPMDs, patients with oral cancer, and healthy controls from the community were recruited to determine the effects of APE1 polymorphisms on malignant transformation, overall survival, and genetic susceptibility, respectively. RESULTS The APE1 Asp148Glu polymorphisms significantly correlated with a high hazard ratio for OPMD malignant transformation (adjusted hazard ratio [AHR] = 2.29; 95% confidence interval [CI] = 1.44-3.74) and low overall survival in oral cancer patients (AHR = 1.71, 95% CI = 1.11-2.56) according to follow-up and survival analysis. However, APE1 polymorphisms did not significantly correlate with development of oral cancer in the case-control study and logistic regression analysis. CONCLUSIONS These results indicate that APE1 Asp148Glu polymorphisms may have indirect roles in increasing the OPMD malignant transformation rate and in decreasing overall survival in oral cancer patients.

Introduction: Oral leukoplakia, the most common potentially malignant oral disorder (PMOD) may progress to oral squamous cell carcinoma (OSCC). Although, the current standard of care for assessing its malignant potential remains histological examination and assessing the severity of dysplasia, DNA ploidy analysis has been suggested as a surrogate marker to predict the behaviour of PMODs. Objectives: To detect aneuploidy and to correlate ploidy status with different grades of dysplasia in both tissue and cytology samples to predict the behaviour of these potentially malignant disorders and to assess the diagnostic utility of cytology samples for ploidy analysis. Methodology: After obtaining ethical clearance and consent, tissue and cytology samples of leukoplakia were collected and grouped based on the dysplastic findings into low-risk (n=20) and high-risk (n=20). DNA ploidy analysis was done using high resolution flow cytometry and its diagnostic utility was assessed. Results: Diagnostic utility was expressed in terms of sensitivity, specificity, PPV and NPV. On comparing the ploidy status of individual cases between tissue and cytology samples, cytology was able to accurately determine the ploidy status in majority of the cases. In the low-risk group, cytology had a sensitivity and specificity of 100% and a PPV and NPV of 100% with an overall diagnostic accuracy of 100%. Among the high-risk group, cytology had a sensitivity of 80% and specificity of 100% with a PPV of 100% and NPV of 83.33% and had an overall diagnostic accuracy of 90%. Combining both groups together, it had a sensitivity of 85.71% and specificity of 100% with a PPV of 100% and NPV of 92.31% and had an overall diagnostic accuracy of 94.74%. Conclusion: Overall, this study showed a positive correlation between cytology and tissue samples and ploidy and grade of dysplasia and cytology proved to be a simple and efficient with a reasonable diagnostic value.

Background: Oral cancer is one of the life threatening disease which requires an availability of a biomarker for its early detection and also for effective treatment strategies. The current study is done to evaluate the efficacy of one such biomarker i.e. TNF- α as an indicator for oral precancer and oral cancer. Objectives: To evaluate the efficacy of Tumour necrosis factor - alpha (TNF)-α as a salivary biomarker in histopathologically diagnosed cases of oral leukoplakia and Oral squamous cell carcinoma. To correlate the levels of TNF- α with varying histologic grading in Oral Squamous Cell Carcinoma and dysplasia grading in Oral leukoplakia or Hyperkeratosis. Materials and Methods: The study group included 90 subjects that were divided into three groups. OSCC (n=30), leukoplakia (n=30) and controls (n=30). Cases were selected based on inclusion and exclusion criteria of the study. Salivary samples were then collected from all three groups. Salivary levels of TNF-α were estimated using Enzyme Linked Immunosorbent Assay (ELISA). The data on concentration gradients obtained were subjected to appropriate statistical analysis. Results: The results of the present study demonstrated higher levels of salivary TNF-α in individuals with OSCC compared to leukoplakia and healthy control subjects with a high level of statistical significance. ROC curve analysis along with diagnostic parameter calculation also revealed that salivary TNF-α to be a better medium for detecting OSCC. There is also an increase in the salivary TNF-α levels with increase in the histological grade of differentiation in OSCC as well as leukoplakia. Conclusion: The present study concludes that salivary TNF – α can be used as a prognostic biomarker of OSCC. In view of the elevated levels of TNF – α in saliva of individuals with severe dysplasia, it can also be used to monitor the malignant transformation to leukoplakia to OSCC.

Objectives To elucidate the risk of malignant transformation to invasive oral cancer by subtypes of oral potentially malignant disorders (OPMD) and to examine the independent effects of risk factors, particularly alcohol drinking, by subtype based on a nationwide oral cancer screening program targeting at general population with habits of smoking and/or betel quids chewing. Materials and methods The total of 8501 subjects diagnosed as different subtypes of OPMDs from the Taiwanese screening program between 2004 and 2009 were followed up over time to ascertain the occurrence of invasive oral cancer. The hazard ratios of malignant transformation were estimated by using Cox proportional hazards regression model. Results The overall malignant rate (per 1000 person-years) to oral cancer was 8.4 (407 incident cases with an average of 5.7 years of follow-up). The highest rate was noted in exophytic verrucous hyperplasia (33), followed by erythroplakia (11.8), erythroleukoplakia (10.7), oral submucous fibrosis (OSF) (8.6), and leukoplakia (5.4). After adjusting for confounders, exophytic verrucous hyperplasia still had a 5.69 (4.47–7.24) times risk compared with leukoplakia. The corresponding figures for erythroplakia, erythroleukoplakia, and OSF were 2.25 (1.31–3.89), 2.00 (1.13–3.53), and 1.63 (1.29–2.06), respectively. Alcohol drinking elevated the overall risk of malignant transformation by 23% (1–52% and also triggered a higher risk in OSF (aHR = 1.62 (1.06–2.47)). The higher risk attributed to betel quids chewing was noted for exophytic verrucous hyperplasia (aHR = 4.23 (1.55–11.55)). Conclusions The risk of malignant transformation to oral cancer varied with the subtypes of OPMD and was elevated in OSF and verrucous hyperplasia attributed to alcohol drinking and betel quids, respectively.

Objectives: The present observational study was conducted with an aim to evaluate the efficacy of diode laser in management of homogenous oral leukoplakia (OL) and reticular oral lichen planus (OLP), so that these potentially malignant disorders can be limited and further malignant transformation can be prevented. Further the assessment of associated postoperative complications after laser therapy was also carried out. Study Design: Present study was carried out using diode laser 810nm on 60 subjects, of whom 30 subjects were of homogenous OL and 30 subjects were of reticular OLP aged between 20 – 60 years, the diagnosis of which was histopathologically confirmed. Results: Of the 60 subjects none complained of pain during and immediately after surgery with no bleeding at any stage of the procedure. By the end of 3rd day post operative most subjects reported no pain and swelling and very few subjects had negligible pain and swelling when evaluated. On subsequent follow-up of 1,2 and 4 week(s) none of the subject reported of pain, swelling or bleeding and it was noted that all the areas treated with laser had healed without scarring with no signs of recurrence. Fibrosis was seen in two male patients and one female patient treated for OL and OLP respectively. Conclusion: Patient compliance and contentment without any postoperative complications were observed to be of high degree in the present study. Thus diode laser can be considered as a best alternative to conventional surgical treatment modality in managing OL and OLP and preventing its further transformation.

Objectives The main objectives of this study were to investigate the detection rate of high-risk human papillomavirus types 16 and 18 (high-risk HPV16/18) in oral potentially malignant disorders (OPMDs) including oral leukoplakia (OL) and oral lichen planus (OLP) in a Thai population and their associations with demographic, risk habits, and clinicopathologic features. Methods Paraffin-embedded formalin-fixed specimens from 101 OL and 59 OLP patients with patients' demographic, risk habits, and clinicopathologic data were collected. Conventional qualitative polymerase chain reaction was used to detect high-risk HPV16/18 DNA. Associations between high-risk HPV type 16/18 and demographic, clinicopathologic, risk factors (tobacco and alcohol uses) of OPMDs were analysed by Chi-square or Fisher's exact test. The results with p value less than 0.05 were considered statistically significant. Results HPV16/18 DNA was found in both OL and OLP groups with the detection rate of 19.8% and 18.6%, respectively. Approximately 90% of high-risk HPV were HPV18 subtype. Additionally, in OL group, high-risk HPV was found more frequently in patients with moderate/severe dysplasia than that in mild dysplasia. Interestingly, in OLP group, high-risk HPV was only detected in atrophic/ulcerative subtypes. None of risk factors was associated with high-risk HPV. Conclusions Approximately 19% of OPMDs were HPV16/18-positive. HPV18 DNA was predominantly detected in both OL and OLP patients (90%). Additionally, the detection rate of high-risk HPV was higher in more severe dysplastic cases of OL and more clinically severe cases of OLP.

Objectives To investigate the available evidence on the malignant transformation (MT) of oral proliferative verrucous leukoplakia (PVL). Material and methods We searched six main electronic and three grey literature databases in a two-phase process. Cohort studies investigating MT of PVL were eligible for inclusion. The risk of bias (RoB) was assessed using a specific tool developed by the Joanna Briggs Institute. Proportion meta-analyses were performed using a random-effects model. Results Study selection resulted in the inclusion of 17 studies. The pooled proportion of MT was 43.87% (95% CI = 31.93-56.13). Females (64.02%, 95% CI = 54.87-72.75) were more affected by PVL than males (35.98%, 95% CI = 27.25-45.13). Gingiva (39.6%) and buccal mucosa (21.6%) were the most frequent PVL sites. No conclusive results were found between MT and sex or age distribution, tobacco, or alcohol consumption. Gingiva was the most common site for MT (39.9%), and the most frequent histopathological subtype was conventional squamous cell carcinoma (62.1%). Four studies were classified as low, nine as moderate, and four as high RoB. Conclusion The MT pooled proportion was 43.87%. Among OPMDs, PVL has the highest risk to transform to malignancy. Development and agreement on diagnostic criteria for PVL would reduce the heterogeneity among future studies.

Prior studies have established the carcinogenic role of HPV16 and also demonstrated its unique biological behavior in cervical and oropharyngeal squamous cell carcinoma (OPSCC) but its role in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) is not well explored. Therefore, in the present study, we assessed HPV16 prevalence using PCR and Anti-HPV16 antibodies for the first time and correlated its biological behavior using p16(INK4a) and Ki67 proliferation index (PI) in OL, OSCC, and OPSCC. This study included 63 subjects comprising of 25 OL, 26 OSCC, and 12 OPSCC cases. Exfoliated cells were collected and processed for PCR followed by immunohistochemistry with primary antibodies p16(INK4a), Anti-HPV16, and Ki67. The expressions were evaluated and statistical analysis included Chi-square and Spearman’s test. Cumulatively 37% (OL—7%, OSCC—14% & OPSCC—16%) of cases showed positive PCR expression. PCR positivity was observed to be significantly higher (p 0.00) in OPSCC (9/12) than OSCC (9/26) and OL (5/25) cases. Overall immunohistochemical expression of p16(INK4a), Anti-HPV16, and Ki67 were significantly (p 0.02) higher in HPV16 (PCR) positive cases. HPV16 + OSCC cases showed higher grades of p16(INK4a) and Ki67 expression. We have demonstrated a prevalence of HPV16 in OL, OSCC, and OPSCC through PCR, which may be concluded as a gold standard for the detection of HPV16 DNA.

Oral leukoplakia (OL), a potentially malignant disorder, recurs in 40% of cases after surgical removal. Recurrence is a risk factor for malignant transformation. We aimed to examine the prognostic significance of four biomarkers related to cell proliferation: p53, p63, podoplanin (PDPN) and Ki-67 in predicting recurrence. Formalin-fixed-paraffin-embedded specimens from excised OL (n = 73, 33 recurrent; 40 non-recurrent) were collected in a prospective study. Immunohistochemistry was used to visualise expression of p53, p63, PDPN and Ki-67. Image analysis software was used for quantification of p53-, p63- and Ki-67-expressing cells, while PDPN was analysed visually. The expression of all four proteins were higher in recurrent compared with non-recurrent OL, only expression of p53 was statistically significant. In uni- and multivariable Cox regression analyses of individual markers, expression of p63 was significantly associated with higher recurrence risk (p = 0.047). OL with a combined high expression of both p53 and p63 had a significantly higher risk to recur [Log Rank, p = 0.036; multivariate Cox, HR: 2.48 (1.13–5.44; p = 0.024)]. Combination of p53 and p63 expression may be used as a prognostic biomarker for recurrence of OL.

Background Certain oral bacterial pathogens may play a role in oral carcinogenesis. We assessed the feasibility of conducting a population-based study in India to examine the distributions and levels of Porphyromonas gingivalis, Fusobacterium nucleatum and Prevotella intermedia in relation to oral leukoplakia (a potentially malignant disorder) and other participant characteristics. Methods This exploratory case-control study was nested within a large urban Indian cohort and the data included 22 men and women with oral leukoplakia (cases) and 69 leukoplakia-free controls. Each participant provided a salivary rinse sample, and a subset of 34 participants (9 cases; 25 controls) also provided a gingival swab sample from keratinized gingival surface for quantitative polymerase chain reaction (qPCR). Results Neither the distribution nor the levels of pathogens were associated with oral leukoplakia; however, individual pathogen levels were more strongly correlated with each other in cases compared to controls. Among controls, the median level of total pathogens was the highest (7.55×104 copies/ng DNA) among persons of low socioeconomic status. Salivary rinse provided better DNA concentration than gingival swab for qPCR analysis (mean concentration: 1.8 ng/μl vs. 0.2 ng/μl). Conclusions This study confirms the feasibility of population studies evaluating oral microbiome in low-resource settings and identifies promising leads for future research.