Etiology Of Oral Cancer Research Articles

Oral Cancer Knowledge, Practices, and Attitudes: A Survey of Libyan Dentists

Dentists play an important role in early detection of oral cancerous lesions. several studies indicate that dentists lack knowledge in oral cancer etiology and diagnosis. Role in the control studies assessing dentists' oral cancer awareness in Libya are lacking. Objectives: This study examined the oral cancer awareness and practice among dentists in Libya. Materials and methods: : Administered questionnaires were distributed on dentists working in private and public clinics in the city of Benghazi. Participants’ responses to the questionnaire were analyzed using descriptive and analytical statistics. Results: Three hundred dentists returned completed questionnaires; 237 (79%) females and 63 (21%) males and most of them were under 40 years old 227 (75.7%). Although most dentists were knowledgeable about the most common site, type, and screening method of oral cancer, only about half of the dentists were aware of tobacco as the main risk factor and biopsy as the most proper diagnostic technique for oral cancer. Despite that 86% of the dentists reported that they perform mucosal examination as part of their routine dental examination, about half of the dentists reported lack of confidence in detecting oral cancer and most dentists expressed need for further education and training in this area. Conclusion: Overall, this study highlighted the importance of introducing continuous education and training programs to dentists which could increase oral cancer prevention and survival rates among oral cancer patients.

Major outcomes of dental implants in oncological patients: a concise systematic review

Introduction: The etiology of oral cancer is multifactorial resulting from several factors that predispose to the development of this pathology. The rehabilitation of oral functions after jaw surgery in patients with oral cancer is a goal that is often difficult to achieve. Dental implants offer a mechanism to provide stability to prostheses. Objective: This study aimed to present the main outcomes of dental implants in cancer patients. Methods: The systematic review rules of the PRISMA Platform were followed. The search was carried out from February to May 2023 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases, using articles from 2013 to 2023. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 118 articles were found, 34 articles were evaluated in full and 14 were included and developed in this systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 32 studies with a high risk of bias and 32 studies that did not meet GRADE. It was concluded that implants inserted into irradiated bone showed significantly lower survival. Head and neck radiotherapy has always been considered a risk factor for rehabilitation with dental implants. However, recent data suggest that the overall 5-year implant survival in irradiated patients may be greater than 90%.

A Genome-Wide Association Study Identified Novel Genetic Susceptibility Loci for Oral Cancer in Taiwan.

Taiwan has the highest incidence rate of oral cancer in the world. Although oral cancer is mostly an environmentally induced cancer, genetic factors also play an important role in its etiology. Genome-wide association studies (GWAS) have identified nine susceptibility regions for oral cancers in populations of European descent. In this study, we performed the first GWAS of oral cancer in Taiwan with 1529 cases and 44,572 controls. We confirmed two previously reported loci on the 6p21.33 (HLA-B) and 6p21.32 (HLA-DQ gene cluster) loci, highlighting the importance of the human leukocyte antigen and, hence, the immunologic mechanisms in oral carcinogenesis. The TERT-CLMPT1L locus on 5p15.33, the 4q23 ADH1B locus, and the LAMC3 locus on 9q34.12 were also consistent in the Taiwanese. We found two new independent loci on 6p21.32, rs401775 in SKIV2L gene and rs9267798 in TNXB gene. We also found two suggestive novel Taiwanese-specific loci near the TPRS1 gene on 8q23.3 and in the TMED3 gene on 15q25.1. This study identified both common and unique oral cancer susceptibility loci in the Taiwanese as compared to populations of European descent and shed significant light on the etiology of oral cancer in Taiwan.

Correlation of histopathological patterns of OSCC patients with tumor site and habits

IntroductionOral cancer is considered a major global public health problem. The causes of OSCC are tobacco, alcohol, viral infections such as EBV, HPV, and herpes simplex virus, poor oral hygiene (including sharp teeth and decay), ill-fitting denture, ultraviolet (UV) exposure, nutrition, and genetic predisposition. The etiology of oral cancer varies in different populations due to area-specific etiological factors.ObjectiveFinding a correlation of histopathological pattern to the tumor site and habits as an outcome of OSCC.MethodsThis cross-sectional study was conducted in Karachi, Pakistan. A total of 100 known cases of an oral squamous cell carcinoma were diagnosed with the help of biopsy reports and were examined for histopathologic features, site of the lesion, and risk habits.Results48 years was the mean age at the time of diagnosis with a distribution of 61% men and 39% women. The frequently affected site was buccal mucosa and the prime risk habit was gutka followed by betel quid. Histologically, the degree of differentiation shows that moderately differentiated OSCC was most commonly present, while the most prevalent histopathological pattern was spindle cell carcinoma. The statistical relation between lesion site and tobacco habits was found to be significant with a p value (p = 0.01).ConclusionRates of oral squamous cell carcinoma are higher in males than females with a mean age at the time of diagnosis being less than 50 years. Frequently placing gutka in the buccal vestibule against buccal mucosa is responsible to make buccal mucosa the most common tumor site. This study provides baseline information regarding habits.

Investigation of the incidence of oral cancer in the municipalities of the state of Sao Paulo-Brazil: a retrospective observational cross-sectional study

Introduction: The etiology of Oral Cancer (OC) is multifactorial, resulting from several factors that predispose to the development of this pathology, with a high incidence and mortality, and is among the 10 most common pathologies in the world. Objective: It was to carry out a retrospective longitudinal observational study on the incidence of oral cancer in patients treated at public health units in the municipalities of the State of Sao Paulo-Brazil, as well as to present the main clinical and demographic characteristics of these patients. Methods: This study followed a retrospective observational cross-sectional model (2018-2022), following the rules of clinical research of the STROBE. The present study used the database of the public health system in Brazil on the incidence and prevalence of oral cancer in health units in 467 municipalities in the State of São Paulo-Brazil, whose data are available for public consultation and do not require approval. by the research ethics committee. Participants with oral cancer records of different ethnicities, aged over 20 years, and of both genders were included. Participants who had missing registration data were excluded. For data analysis, the database was built in a Microsoft Excel spreadsheet, which was exported to the Minitab 18® statistical program. One-Way ANOVA with p>0.05 was applied without a statistical difference in the CI95%. Results: The total number of municipalities in the State of São Paulo-Brazil analyzed was 467. Suspected oral malignancy did not present a significant statistical difference between the years 2018 and 2019 (0.33% vs. 0.30%), with p>0.05 in CI95 %. The highest incidences of suspected oral malignancy occurred in 2018 and 2019. In addition, it was evidenced that the most frequent histological type was squamous cell carcinoma in all the years analyzed. Also, bad habits such as alcoholism, smoking, excessive exposure to the sun, and also genetic predisposition, the presence of HPV did not show to influence statistically the occurrences of oral neoplasms. Conclusion: Based on the objective of this study, the incidence of oral cancer in the municipalities of the state of São Paulo-Brazil was higher in the years 2018 and 2019, regardless of the action of predictors such as smoking, alcohol consumption, HPV, genetic predisposition and age. However, further studies need to be carried out in the periods from 2020 to 2022 to know the population that was absent due to the COVID-19 pandemic.

Association of EZH2 Genotypes With Oral Cancer Risk.

The over-expression of enhancer of zeste homolog 2 (EZH2) protein is found in oral cancer tissues. However, the genetic role of the enhancer of EZH2 in the etiology of oral cancer is unknown. The aim of this study was to evaluate the association of EZH2 genotypes with oral cancer risk among Taiwanese. Three polymorphic variants of EZH2, rs887569 (C to T), rs41277434 (A to C), and rs3757441 (T to C), were analyzed regarding their association with oral cancer risk among 958 oral cancer patients and the same number of healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In addition, the interaction of EZH2 rs887569, rs41277434, and rs3757441 genotypes with personal behaviors such as smoking, alcohol drinking, and betel quid chewing were also examined. The EZH2 genotypes rs887569, rs41277434, and rs3757441, were not significantly associated with oral cancer risk (p for trend=0.1735, 0.5658, and 0.4606, respectively). The analysis of allelic frequency distribution also supported the findings that the variant alleles at EZH2 rs887569, rs41277434, and rs3757441 may not serve as determinants of oral cancer risk (all p>0.05). There was no interaction between EZH2 rs887569, rs41277434, or rs3757441 genotypes with personal smoking, alcohol drinking or betel quid chewing behaviors. EZH2 genotypes cannot predict oral cancer risk in Taiwan.

Effects of streptococcus mutans on the expression of inflammatory cytokine TNF-α and p53 by human gum fibroblast cells

Oral bacteria are involved in the etiology of oral cancer. In this study, Streptococcus mutans were examined for the gene’s expression involved in inflammation, carcinogenicity, and tumor inhibition among these species. This study aimed to determine the association between microbiome and oral cancer. Human Gingival Fibroblast (HGF) and S. mutans were cultured on their relative mediums. Then, HGF was preconditioned whit several concentrations of S. mutans extract, and the cell viability was determined by MTT assay. HGF cells were treated with an optimum dose of bacterial extract, and then the total RNA was extracted from treated and untreated HGF cells. Lastly, p53 and TNF-α gene expression was evaluated by Real-Time PCR. The results implied that in the S. mutans presence, TNF-α and P53 genes expression in the HGFs increased and decreased, respectively. This result suggests that S. mutans may invasively enhance oral cancer cells. These findings more designate the association between oral microbiota and oral cancer. This relation is of clinical importance for the prevention and treatment of oral cancer in the future. Keywords: streptococcus mutans; human gingival fibroblast (HGF); oral cancer; P53; TNF-α.

Determining the Risk Factor of Oral Cancer on Chewing Smokeless Tobacco Kharra: A Case–control Study

Background: Oral cancer is the sixth most common cancer globally; however, the incidence is much higher in the developing countries, including Pakistan, India, Sri Lanka. The etiology of oral cancer is multifactorial with majority of the cases attributable to separate and combined use of tobacco (smoked and smokeless), excessive alcohol consumption, betel quid, and betel quid substitutes. Among this, Kharra chewing (areca nut and tobacco) is the most prevalent addiction and the most common risk factors of oral cancer in central India.
 Objectives: To evaluate the risk of oral cancer associated with kharra users and non-tobacco user. To evaluate the association for the risk factors of oral cancer with kharra and non-tobacco user.
 Methodology: A hospital based case control study will be carry out in the study, the study will be conducted among the patient who had confirmed diagnosis of oral cancer and visited the hospital in AVBRH and SPDC Sawangi (Meghe) Wardha. Non- probability convenient sampling technique will be used for selecting the sample. The structured questionnaire will be used for collection of the data.
 Expected Results: This study is mainly planned to evaluate the effects of Kharra chewing on oral cancer risk with the help of structured questionnaire. Hence, it is expected to identify the effects of Kharra chewing on the risk of oral cancer.

Periodontitis as a risk for oral cancer: a case\u2013control study

BackgroundThe aetiology of oral cancer is multifactorial, as various risk factors (genetics, socioeconomic and lifestyle factors) contribute to its development. Data in the literature suggest that people with periodontal disease have an increased risk of developing oral cancer, and the severity of periodontitis correlates with the appearance of oral squamous cell carcinoma. The aim of this study was to revise the non-genetic risk factors that may influence the development of OC, while focusing on the dental and periodontal status and OH.MethodsTwo hundred patients (hundred diagnosed with oral cancer and hundred without oral cancer) were enrolled in our case–control study, to evaluate the association between oral cancer and the presence and severity of periodontitis, while examining several risk factors that might be responsible for oral cancer formation. A questionnaire customised for oral cancer patients was used to obtain the socioeconomic and lifestyle risk factors that may influence the development of oral squamous cell carcinoma. The dental and periodontal status along with the level of oral hygiene was recorded quantitatively. The chi-square and Mann–Whitney tests and logistic regression were used for the statistical analysis.ResultsBy considering both the case and the control groups, a significant correlation was found between the incidence of oral cancer and some socioeconomic factors and lifestyle habits, such as the sex, age, education and alcohol consumption of an individual. The mean value of the Silness-Löe plaque index was significantly higher in the case population. The number of completely edentulous patients was higher among the oral cancer population. The incidence of oral cancer was 57.1% in patients with periodontal disease. In comparison, the incidence of oral squamous cell carcinoma was only 28.6% among the patients without periodontitis. Most of the oral cancer patients (72.1%) had stage 4 periodontitis. On the other hand, the vast majority of the control group (51.6%) had stage 2 periodontitis.ConclusionPeriodontitis can be an individual risk factor for oral cancer development. Periodontally compromised individuals should be strictly monitored, especially those with severe periodontitis and coexisting lifestyle risk factors. Maintaining their periodontal health in at-risk patients can minimize cancer risks.

Oral Cancer Awareness Among Dental Patients in Benghazi, Libya : A cross- sectional Study

Background: Oral cancer is considered as one of the major public health problems in the coming decades. It is one of the most life-threatening conditions, and it is ranked as the 15th most common cancer in the world. Lack of awareness about the etiology, signs and symptoms of oral cancer might be the main causes of its delayed detection. Therefore, evaluation of patient’s awareness towards oral cancer can play an important role in early detection and will lead to better prognosis. The aim of this study is to assess the level of dental patients’ awareness towards oral cancer at Faculty of Dentistry, University of Benghazi.
 Materials and Methods: A cross sectional study was conducted on dental patients during the academic year 2018-2019 at Faculty of Dentistry, University of Benghazi. Patients were surveyed for oral cancer awareness by using a pre-tested, self-administered questionnaire. The data was entered and tabulated into a computer using the Statistical Package for Social Science (SPSS Version 20 for Windows, SPSS Inc. Chicago, IL). Data analysis included descriptive statistics.
 Results: The response rate was 87.4%. The study popula­tion comprised of 39.3% females and 60.7% males. Low educated patients represented 23.2% of participants. The majority of them (77.1%) have heard about the term of oral cancer with the mass media constitute 38.3% of their information sources. Less than half of patients had the idea that growth of abnormal tissue and continuous pain in jaw are considered as early symptoms of the cancer. Only 23.9% of participates believed that smoking is considered as a risk factor of oral cancer.
 Conclusion and Recommendation: There is a lack in the awareness of early signs, symptoms, and etiology of oral cancer. Therefore, an intensive public education program to recognize the early warning signs, symptoms and etiologies of the cancer is recommended. In additions, individuals should be encouraged for self-oral examination and regularly visit the dental clinics. This would play an important role in early recognition of the cancer and better prognosis would be expected.

A review of the aetiology of oral cancer in the Sudan

Objectives: To focus the light on the aetiology of oral cancer in the Sudan. Numerous reports have shown that the incidence of oral cancer worldwide is on increase. The rising incidence of oral cancer, with the absence of the well established risk factors, has wrung alarm bells. Material and Methods: Website search (Pubmed central and google scholar) for publications addressing the aetiology of oral cancer in the Sudan, in addition to snuff dipping (Tombak) which is a common habit in Sudan. Results: During initial search 420 publications were identified, on exclusion of studies related to other countries and other body tumours 36 studies discussing the aetiology of oral cancer in the Sudan were examined. Conclusions: Toombak is the major contributing factor for oral cancer in the Sudan. The role of other contributing factors such as viruses other than Human Papilloma Virus, other types of tobacco such as smoked tobacco and alcohol still need more investigations.

Association of Diabetes with Oral Cancer- an Enigmatic Correlation.

Introduction:Association of diabetes mellitus (DM) with head and neck cancers (HNC) is still controversial. In some studies, diabetic patients had an increased risk of cancer at some HNC subsites like oral cancer, while in other studies this risk was decreased. So, the present study aims to evaluate the association of diabetes mellitus, oral cancer with and without metformin and the role of habits in association with DM and metformin in the etiology of oral cancer. Materials and methods:This study was undertaken in the Kamineni Institute of Dental Sciences in collaboration with MNJ Institute of Oncology and Regional Cancer Centre, Hyderabad. The study includes 2 main groups, they are 500 Oral cancer patients and Control group includes 500 age and gender-matched patients with habits without any oral precancerous lesion/conditions. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression. Results:Out of 1000 subjects inverse relation of DM with oral cancer was observed. On comparison between oral cancer, diabetes and habits in study group and control group, decreased risk was observed with smokers (OR: 1.131and 95%CI: 0.68 -1.86) and non-chewers (OR: 2.43 and 95% CI: 1.31 - 4.49) and non-alcoholics (OR: 1.78 and 95% C.I:1.18 - 2.68). Metformin use among diabetic participants was associated with a decreased risk of oral cancer (OR: 0.51 and 95% C.I: 0.33 - 0.77). A negative association was observed in smokers (OR: 0.19 and 95% C.I.: 0.078 - 0.459), non-chewers (OR: 0.24 and 95% C.I : 0.11- 0.53) and non-alcoholics (OR: 0.46 and 95% C.I. : 0.29 - 0.727).Conclusion:Thus the present population based study results suggest an inverse association of DM and oral cancer with metformin and negative association of habits with DM and Metformin in etiology of oral cancer.

Hyperplasia of Wistar rat tongue mucosa due to exposure to cigarette side-stream smoke

Background: Hyperplasia, a condition whereby an excessive number of cells are produced due to their uncontrolled division, represents a common symptom of carcinogenesis. Cancer is a physical manifestation of cell malignancy resulting from abnormal proliferation. Globally, oral cancer currently constitutes the sixth largest lethal form of the condition. The most common etiology of oral cancer is tobacco of which cigarettes are the most popular related product. The health risks associated with cigarette smoke not only affect active smokers but also individuals who ingest it passively. Sidestream smoke comes from the lighted end of a burning tobacco product such as a cigarette, pipe or cigar and contains nicotine and many harmful cancer-causing chemicals. Inhaling sidestream smoke increases the risk of lung and other types of cancer. Purpose: The purpose of this study was to understand how sidestream cigarette smoke initiates precancerous changes, in this case hyperplasia, in the oral mucosa epithelium of Wistar rats. Methods: The subjects were divided into three groups, a 4-week treatment group (P1), an 8-week treatment group (P2), and a control group (K), each consisting of ten subjects. The subjects were exposed to a daily two-cigarette dose of smoke. The experiment used a post-test only control group design. All samples were sacrificed during the fourth and eighth weeks. Haematoxylin-eosin staining was performed on the tongues of the Wistar rats to establish the presence of hyperplasia. Data was analyzed using a one-way ANOVA test. Results: After the Wistar rats had been exposed to cigarette smoke, an increased degree of epithelial cell proliferation (hyperplasia) showed a significant difference with a p-value <0.05 during the eighth week. Conclusion: Exposure to cigarette sidestream smoke induces increased epithelial cell proliferation (hyperplasia) in Wistar rats.

Progress in Drug and Formulation Development for the Chemoprevention of Oral Squamous Cell Carcinoma: A Review

Cancer is a life-threatening global problem with high incidence rates. Prioritizing the prevention of cancer, chemopreventive agents have drawn much attention from the researchers. This review focuses on the discussion of the progress in the development of chemopreventive agents and formulations related to the prevention of oral cancer. In this perspective, an extensive literature survey was carried out to understand the mechanism, control and chemoprevention of oral cancer. Different patented agents and formulations have also exhibited cancer preventive efficacy in experimental studies. This review summarizes the etiology of oral cancer and developments in prevention strategies. The growth of oral cancer is a multistep activity necessitating the accumulation of genetic as well as epigenetic alterations in key regulatory genes. Many risk factors are associated with oral cancer. Genomic technique for sequencing all tumor specimens has been made available to help detect mutations. The recent development of molecular pathway and genetic tools has made the process of diagnosis easier, better forecast and efficient therapeutic management. Different chemical agents have been studied for their efficacy to prevent oral cancer and some of them have shown promising results. Use of chemopreventive agents, either synthetic or natural origin, to prevent carcinogenesis is a worthy concept in the management of cancers. Preventive measures are helpful in controlling the occurrence or severity of the disease. The demonstrated results of preventive agents have opened an arena for the development of promising chemopreventive agents in the management of oral squamous cell carcinoma.

CORRELATION OF HPV16 DETECTION AND P16 EXPRESSION IN ORAL SQUAMOUS CELL CARCINOMA

Objectives Oral cancer etiology is multifactorial and the main risk factors are tobacco chewing and smoking along with alcohol consumption and viruses. In the current study from a South Indian population, we sought to determine the role of HPV 16 in the pathogenesis, its concordance with p16 over expression in OSCC. Preliminary examination on FFPE embedded OSCC (n = 297) sample was observed by H & E staining, and cases showing cytological changes were selected. Findings HPV 16 DNA prevalence were assessed by Conventional PCR method which showed 128 out of 297 samples positive for HPV16 DNA. Further, the frequency distribution of HPV 16 E6/E7 in 128 tissues was evaluated by qPCR which showed 97 samples were positive for HPV16 E6 qPCR and 98 samples positive for HPV16 E7 qPCR. For the same 128 samples immunohistochemistry was conducted for p16 evaluation.Out of 128 tissue samples, 19 tissue samples were found to be positive for p16 overexpression (+++). Evaluation of mRNA expression of E6 and E7 in the 19 samples was estimated by flow-cytometry, which revealed only 7 samples positive for the mRNA expression. There was no correlation between p16 expressed (+++) samples and quantification of HPV16 mRNA expressions. From these investigations the role of HPV in the etiology, pathogenesis of OSCC was not established. Conclusion This led to the performance of meta-analysis in which studies pertaining to HPV-related OSCC evaluated by application of conventional and qPCR, flow cytometry and IHC for the detection of DNA, mRNA and p16 overexpression, respectively were included. The results obtained were indicative that HPV prevalence in the oral cavity is low and unlikely to play a major significant or decisive role in the etiology, pathogenesis of OSCC. Our results were in accordance with the meta analysis results.

Surgical Management of Oral Squamous Cell Carcinoma in Dhaka Dental College Hospital; 31 patients

Cancer is a major cause of death throughout the world. Oral cancer is one of the six most frequently occurring cancer.1 In Bangladesh, the number of new cancer cases of whole body per year is about 200000 of which oral cancer is about 20%.2 In our neighboring country India, accounts for thirty-five percent of all newly diagnosed cancers in men. The etiology of oral cancer is well established in most instances with consumption of tobacco in any form and alcohol being the most common etiologic agents. Recently, however, exposure to the human papilloma virus has been implicated in young patients with oral carcinoma. The exact mechanism of carcinogenesis in this setting remains to be elucidated .3 Surgery is the most well established mode of initial definitive treatment for a majority of oral cancers. The factors that affect the choice of treatment are related to the tumor and the patient. Primary site, location, proximity to bone and depth of infiltration are factors, which influence particular surgical approach. Advanced reconstructive techniques that allow free transfer of soft tissue and bone improve the functional and aesthetic outcomes following major ablative surgery .Over the course of the past thirty years there has been improvement in the overall survival of patients with oral carcinoma largely due to the improved understanding of the biology of local progression, early identification and treatment of metastatic lymph nodes in the neck and employment of adjuvant post-operative radiotherapy or chemotherapy. Either the role of surgery in oral cancer has evolved with integration of multidisciplinary treatment approaches employing chemotherapy and radiotherapy sequentially or concurrently .Surgical expertise is required for rehabilitation of functional and aesthetic defects created by initial treatment of cancer. Thus, surgery and services of a surgeon remain central to the management of oral cancer.4 A cross sectional study of 31patients undergoing surgery for the treatment of oral squamous cell carcinoma was carried out at Department of Oral & Maxillofacial Surgery ,Dhaka Dental college & hospital from May 2016 to July2017. Here 31 patients, of them male 13 and female 18 having 31 to 80years age ranges of oral squamous cell carcinoma who underwent surgery and reconstruction were included in this study. All patients were referred to oncologist after surgery. Aim of this study was to assess the status of disease, to provide the patient surgical treatment as a first line therapy, to find out any post-operative complications.
 Update Dent. Coll. j: 2018; 8 (2): 10-13

The role of alcohol in the aetiology of oral Cancer: A study done in southern India

The role of alcohol in the aetiology of oral Cancer: A study done in southern India

Oral bacterial flora and oral cancer: The possible link?

Oral cancer exhibits multifactorial etiology with tobacco and alcohol long been implicated as the primary risk factors. In addition, betel nut, dietary factors and poor oral hygiene have also been found to have a role in the etiology of oral cancer. Past research has uncovered a great deal of information regarding the association of exogenous bacteria with cancer. However, our definitive knowledge of the oral commensal bacteria and oral cancer link remains inadequate. In the present article, we hypothesize a causal role for oral bacterial flora in oral cancer although an indirect one. We propose that the normal bacterial flora in conjunction with the already established risk factors such as alcohol consumption may play a role in cancer development. The continued exploration of this topic may aid in better understanding of the pathogenesis of oral cancer thereby helping in appropriate treatment and better prognosis.

Signature of genetic associations in oral cancer.

Oral cancer etiology is complex and controlled by multi-factorial events including genetic events. Candidate gene studies, genome-wide association studies, and next-generation sequencing identified various chromosomal loci to be associated with oral cancer. There is no available review that could give us the comprehensive picture of genetic loci identified to be associated with oral cancer by candidate gene studies-based, genome-wide association studies-based, and next-generation sequencing-based approaches. A systematic literature search was performed in the PubMed database to identify the loci associated with oral cancer by exclusive candidate gene studies-based, genome-wide association studies-based, and next-generation sequencing-based study approaches. The information of loci associated with oral cancer is made online through the resource "ORNATE." Next, screening of the loci validated by candidate gene studies and next-generation sequencing approach or by two independent studies within candidate gene studies or next-generation sequencing approaches were performed. A total of 264 loci were identified to be associated with oral cancer by candidate gene studies, genome-wide association studies, and next-generation sequencing approaches. In total, 28 loci, that is, 14q32.33 (AKT1), 5q22.2 (APC), 11q22.3 (ATM), 2q33.1 (CASP8), 11q13.3 (CCND1), 16q22.1 (CDH1), 9p21.3 (CDKN2A), 1q31.1 (COX-2), 7p11.2 (EGFR), 22q13.2 (EP300), 4q35.2 (FAT1), 4q31.3 (FBXW7), 4p16.3 (FGFR3), 1p13.3 (GSTM1-GSTT1), 11q13.2 (GSTP1), 11p15.5 (H-RAS), 3p25.3 (hOGG1), 1q32.1 (IL-10), 4q13.3 (IL-8), 12p12.1 (KRAS), 12q15 (MDM2), 12q13.12 (MLL2), 9q34.3 (NOTCH1), 17p13.1 (p53), 3q26.32 (PIK3CA), 10q23.31 (PTEN), 13q14.2 (RB1), and 5q14.2 (XRCC4), were validated to be associated with oral cancer. "ORNATE" gives a snapshot of genetic loci associated with oral cancer. All 28 loci were validated to be linked to oral cancer for which further fine-mapping followed by gene-by-gene and gene-environment interaction studies is needed to confirm their involvement in modifying oral cancer.

Oral cancer via the bargain bin: The risk of oral cancer associated with a smokeless tobacco product (Naswar).

In the wake of smokeless tobacco (SLT) being advocated as a mean of tobacco harm reduction, it is pertinent to establish individual health risks associated with each SLT product. This case-control study was aimed at assessing the risk of oral cancer associated with a smokeless tobacco product (Naswar). The study was conducted from September 2014 till May 2015 in Khyber Pakhtunkhwa, Pakistan. Exposure and covariate information was collected through a structured questionnaire. Conditional logistic regression was used to calculate odds ratios (OR) along with their 95% confidence intervals (CI). 84 oral cancer cases (62% males) and 174 age- and sex-matched controls were recruited. Ever users of Naswar had more than a 20-fold higher risk of oral cancer compared to never-users (OR 21.2, 95% CI 8.4–53.8). Females had a higher risk of oral cancer with the use of Naswar (OR 29.0, 95% CI 5.4–153.9) as compared to males (OR 21.0, 95% CI 6.1–72.1). Based on this result, 68% (men) and 38% (women) of the oral cancer burden in Pakistan is attributable to Naswar. The risk estimates observed in this study are comparable to risk estimates reported by previous studies on other forms of SLT use and the risk of oral cancer in Pakistan. The exposure-response relationship also supports a strong role of Naswar in the etiology of oral cancer in Pakistan. Although still requiring further validation through independent studies, these findings may be used for smokeless tobacco control in countries where Naswar use is common.