HPV IN ORAL SQUAMOUS CELL CARCINOMA - CHANGING TRENDS IN THE RISK FACTORS AND DEMOGRAPHICS OF ORAL CANCER IN THE INDIAN SUBCONTINENT

Infection with specific pathogens and alterations in tissue commensal microbial composition are intricately associated with the development of many human cancers. Likewise, dysbiosis of oral microbiome was also shown to play critical role in the initiation as well as progression of oral cancer. However, there are no reports portraying changes in oral microbial community in the patients of Indian subcontinent, which has the highest incidence of oral cancer per year, globally. To establish the association of bacterial dysbiosis and oral squamous cell carcinoma (OSCC) among the Indian population, malignant lesions and anatomically matched adjacent normal tissues were obtained from fifty well-differentiated OSCC patients and analyzed using 16S rRNA V3-V4 amplicon based sequencing on the MiSeq platform. Interestingly, in contrast to the previous studies, a significantly lower bacterial diversity was observed in the malignant samples as compared to the normal counterpart. Overall our study identified Prevotella, Corynebacterium, Pseudomonas, Deinococcus and Noviherbaspirillum as significantly enriched genera, whereas genera including Actinomyces, Sutterella, Stenotrophomonas, Anoxybacillus, and Serratia were notably decreased in the OSCC lesions. Moreover, we demonstrated HPV-16 but not HPV-18 was significantly associated with the OSCC development. In future, with additional validation, this panel could directly be applied into clinical diagnostic and prognostic workflows for OSCC in Indian scenario.

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Periodontitis as a risk for oral cancer: a case–control study

BMC Oral Health ◽

10.1186/s12903-021-01998-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

György Komlós ◽

Katalin Csurgay ◽

Ferenc Horváth ◽

Liza Pelyhe ◽

Zsolt Németh

Keyword(s):

Risk Factors ◽

Squamous Cell Carcinoma ◽

Oral Cancer ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Lifestyle Risk Factors ◽

Oral Cancer Patients ◽

Lifestyle Risk ◽

Control Study

Abstract Background The 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. Methods Two 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. Results By 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. Conclusion Periodontitis 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.

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Etiologic factors associated with oral squamous cell carcinoma in non-smokers and non-alcoholic drinkers: a brief approach

Brazilian Dental Journal ◽

10.1590/s0103-64402012000500020 ◽

2012 ◽

Vol 23 (5) ◽

pp. 586-590 ◽

Cited By ~ 21

Author(s):

Fabiana Vargas-Ferreira ◽

Fernanda Nedel ◽

Adriana Etges ◽

Ana Paula Neutzling Gomes ◽

Cristiane Furuse ◽

...

Keyword(s):

Risk Factors ◽

Squamous Cell Carcinoma ◽

Human Papillomavirus ◽

Oral Cancer ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Pubmed Database ◽

Potential Risk Factors ◽

Traditional Risk Factors

Oral squamous cell carcinoma (OSCC) is the fifth most common type of cancer in the world. The effect of some etiological factors is well established in the literature, such as consumption of tobacco and alcohol. However, approximately 15 to 20% of all oral cancer cases occur in patients without the traditional risk factors, reflecting in numerous cases of OSCC in non-smokers and non-alcoholic drinkers. Also, several studies have suggested a possible association between human papillomavirus and OSCC. Under these aspects, the purpose of this study is to address cases of oral cancer in non-smokers and non-drinkers focusing on the role of HPV, thus contributing to improve the diagnosis and monitoring of OSCC. A computer database search was performed using the Pubmed database. The search key words were: epidemiology, oral squamous cell carcinoma, risk factors and human papillomavirus. It is important to assess patients without the potential risk factors, since this knowledge may help identifying other features associated with the occurrence of oral cancer, enabling an appropriate clinical management and monitoring.

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Zinc α-2 Glycoprotein (ZAG) a Novel Biomarker for the Detection of Oral Squamous Cell Carcinoma

Pakistan Journal of Medicine and Dentistry ◽

10.36283/pjmd9-3/015 ◽

2020 ◽

Author(s):

Mehwish Feroz Ali

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Cancer ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Malignant Lesion ◽

Tobacco Consumption ◽

Constant Stimulus ◽

Dysplastic Lesion ◽

Cancerous Lesion

Oral cancer, the most challenging and life threatening disease in the field of dentistry, may start as a reactive lesion due to constant stimulus from tobacco consumption, transform into a pre-malignant lesion (dysplastic lesion) and ultimately develop into a cancerous lesion (Invasive carcinoma). There is a fundamental revolution taking place in the analyzing methods; extraction of biological protein from the saliva rather than from tissues or blood. Several of the biomarkers have been studied with pro-carcinogenic effects like Interleukins (ILs), tumor necrosis factor (TNF) and leptin, but only a few have been stated in the literature, which show anti-cancer characteristics like adiponectin and zinc alpha-2 glycoprotein. This review explored the diagnostic and prognostic values of a biomarkers zinc alpha-2 glycoprotein (ZAG) in adults suspected of oral squamous cell carcinoma (OSCC). The PubMed, EMBASE and Google Scholar were searched for scientific studies reported on the potential mechanism of zinc alpha-2 glycoprotein. All the research articles were selected in which ZAG is applied solely or in conjunction with other biomarkers in oral cancer and other cancers. These literatures were carefully assessed to find out and compile the diagnostic and prognostic values and to inquire therapeutic action of ZAG in the process of carcinogenesis.

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Rediscussing the Role of Traditional Risk Factors in Young Adults With Oral Squamous Cell Carcinoma

Anticancer Research ◽

10.21873/anticanres.14723 ◽

2020 ◽

Vol 40 (12) ◽

pp. 6987-6995

Author(s):

NORBERT NECKEL ◽

MARCO MICHAEL ◽

DANIEL TROELTZSCH ◽

JONAS WÜSTER ◽

STEFFEN KOERDT ◽

...

Keyword(s):

Risk Factors ◽

Squamous Cell Carcinoma ◽

Young Adults ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Traditional Risk Factors

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Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress

International Journal of Oral Science ◽

10.1038/s41368-021-00118-4 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Wen Chen ◽

Chenzhou Wu ◽

Yafei Chen ◽

Yuhao Guo ◽

Ling Qiu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Endoplasmic Reticulum ◽

Oral Cancer ◽

Oral Squamous Cell Carcinoma ◽

Endoplasmic Reticulum Stress ◽

Cell Carcinoma ◽

Squamous Cell ◽

Migration And Invasion ◽

Ceramide Synthase

AbstractC18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma. However, the function of ceramide synthase 1, a key enzyme in C18 ceramide synthesis, in oral squamous cell carcinoma is still unclear. The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer. In this study, we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines. In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide, ceramide synthase 1 knockout was associated with the severity of oral malignant transformation. Immunohistochemical studies showed significant upregulation of PCNA, MMP2, MMP9, and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area. In addition, ceramide synthase 1 knockdown promoted cell proliferation, migration, and invasion in vitro. Overexpression of CERS1 obtained the opposite effect. Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation. Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation. In addition, mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance. Taken together, our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.

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Risk factors for distant metastasis in locoregionally controlled oral squamous cell carcinoma: a retrospective study

Scientific Reports ◽

10.1038/s41598-021-84704-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hirofumi Tomioka ◽

Yuko Yamagata ◽

Yu Oikawa ◽

Toshimitsu Ohsako ◽

Takuma Kugimoto ◽

...

Keyword(s):

Risk Factors ◽

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Distant Metastasis ◽

Significant Risk ◽

Distant Metastases ◽

Cervical Lymph Node Metastasis ◽

Extranodal Extension

AbstractThe control of distant metastasis in oral squamous cell carcinoma is an important determinant of improved prognosis. The study aimed to identify risk factors for distant metastasis in patients with locoregionally controlled oral carcinoma. We identified 982 patients with oral squamous cell carcinoma treated at our hospital between January 2008 and December 2017. After excluding patients with distant metastasis at initial treatment, patients with metastasis to the oral cavity, those receiving palliative treatment, and those lacking follow-up data, 941 patients were selected. Finally, among these 941 patients, 887 with locoregionally controlled oral squamous cell carcinoma were included in the study. Among the 887 patients, 36 had confirmed distant metastasis (4.1%), and the lung was the most common site (31/36 patients, 86.1%). Multivariate analysis showed that the incidence of primary intraosseous carcinoma of the mandible, cervical lymph node metastasis at levels IV and V, and the presence of pathological extranodal extension were significant risk factors for distant metastasis. When treating patients with oral squamous cell carcinoma who are positive for the aforementioned risk factors, the possibility of developing distant metastases must be accounted for, and aggressive treatment should be planned accordingly.

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Role of viruses in oral squamous cell carcinoma

Oncology Reviews ◽

10.4081/oncol.2012.e21 ◽

2012 ◽

Vol 6 (2) ◽

pp. 21 ◽

Cited By ~ 14

Author(s):

Rashmi Metgud ◽

Madhusudan Astekar ◽

Meenal Verma ◽

Ashish Sharma

Keyword(s):

Risk Factors ◽

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Genetic Susceptibility ◽

Squamous Cell ◽

Oncogenic Viruses ◽

Exact Role ◽

Carcinogenic Effects

The etiology of oral squamous cell carcinoma (OSCC) is complex and involves many factors. The most clearly defined risk factors are smoking and alcohol, which substantially increase the risk of oral SCC. However, despite this clear association, a substantial proportion of patients develop OSCC without exposure to them, emphasizing the role of other risk factors such as genetic susceptibility and oncogenic viruses. Some viruses are strongly associated with OSCC while the association of others is less frequent and may depend on co-factors for their carcinogenic effects. Therefore, the exact role of viruses must be evaluated with care in order to improve the diagnosis and treatment of OSCC.

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Salivary LDOC1 is a gender-difference biomarker of oral squamous cell carcinoma

PeerJ ◽

10.7717/peerj.6732 ◽

2019 ◽

Vol 7 ◽

pp. e6732 ◽

Cited By ~ 2

Author(s):

Chung-Ji Liu ◽

Jen-Hao Chen ◽

Shih-Min Hsia ◽

Chiu-Chu Liao ◽

Hui-Wen Chang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Cancer ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Suppressor Gene ◽

Clinicopathological Characteristics ◽

Pcr Analysis ◽

Expression Levels ◽

Low Levels

Background The X-linked tumor suppressor gene LDOC1 is reported to be involved in oral cancer. The detection of biomarkers in salivary RNA is a non-invasive strategy for diagnosing many diseases. The aim of the present study was to investigate the potential of salivary LDOC1 as a biomarker of oral cancer. Methods We determined the expression levels of LDOC1 in the saliva of oral squamous cell carcinoma (OSCC) subjects, and investigated its correlation with various clinicopathological characteristics. The expression levels of salivary LDOC1 were detected in 53 OSCC subjects and 43 healthy controls using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. We used Fisher’s exact test to analyze the correlations between expression levels and clinicopathological characteristics. Results Salivary LDOC1 was significantly upregulated in females with OSCC (p = 0.0072), and significantly downregulated in males with OSCC (p = 0.0206). Eighty-nine percent of male OSCC subjects who smoked expressed low levels of LDOC1. OSCC cell lines derived from male OSCC subjects expressed low levels of LDOC1. Conclusions A high level of salivary LDOC1 expression is a biomarker of OSCC in females. A high percentage of male OSCC subjects who smoke express low levels of salivary LDOC1. A low level of salivary LDOC1 expression is a biomarker of OSCC in males.

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Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1612368113 ◽

2016 ◽

Vol 113 (41) ◽

pp. 11549-11554 ◽

Cited By ~ 43

Author(s):

Jau-Song Yu ◽

Yi-Ting Chen ◽

Wei-Fan Chiang ◽

Yung-Chin Hsiao ◽

Lichieh Julie Chu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Oral Cancer ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Risk Score ◽

Squamous Cell ◽

Low Risk ◽

Healthy Controls ◽

Protein Biomarkers

Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan’s Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.

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