|Year : 2022 | Volume
| Issue : 2 | Page : 46-49
Inflammation and oral cancer
Jaya Singh, Trupti Jain, Rahul Agrawal, Akhilesh Chandra
Department of Oral Pathology and Microbiology, Faculty of Dental Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
|Date of Submission||02-Apr-2022|
|Date of Decision||02-Aug-2022|
|Date of Acceptance||25-Aug-2022|
|Date of Web Publication||19-Dec-2022|
Dr. Jaya Singh
Department of Oral Pathology and Microbiology, Faculty of Dental Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Inflammation is the chief causative agent of many chronic diseases including cancer of all origins. Oral squamous cell carcinoma is the third-most common cancer in India and chronic inflammation plays a pivotal role in tumorigenesis. Early diagnosis is the key to better survival of these patients. Targeted prevention and treatment have been promising avenues in oral cancer management. This review sheds a light on the association between inflammation and oral cancer and the biomarkers associated with cancer progression.
Keywords: C-reactive protein, inflammation, oral squamous cell carcinoma, reactive nitrogen species, reactive oxygen species, serum amyloid A
|How to cite this article:|
Singh J, Jain T, Agrawal R, Chandra A. Inflammation and oral cancer. Int J Oral Health Sci 2022;12:46-9
| Introduction|| |
Oral squamous cell carcinoma (OSCC) along with pharyngeal is the sixth-most common carcinoma in the world and the third-most common cancer in India. Two-thirds of OSCC occur in developing countries. Traditionally, oral cancer was thought to be seen in the older age groups, whereas a study by Sharma et al. proved otherwise, in which it was more prevalent in the second and third decades. Age-adjusted rates of oral cancer in India are high, that are, 20/100,000 population and account for over 30% of all cancers in the country. In men, it is the sixth-most common, and in women, the twelfth-most common carcinoma. It has been propositioned in the past that the buccal mucosa can undergo malignant alterations. Oral potentially malignant disorders have a high propensity to turn into malignancies such as OSCC.
A detrimental retort harmful to humans is inflammation. Metchnikoff for the first time documented the role of inflammation in an individual's defense mechanism and recovery. Inflammation has a pivotal role in indicating the disease process which is why it is considered the keystone in pathology. The classical signs of inflammation include rubor (redness), tumor (swelling), calor (heat), dolor (pain), and functio laesa (loss of function). Celsus in 30–38 B. C. named the first 4 signs, namely, rubor, tumor, calor, and dolor, and Galen in A. D. 130–200 named the last sign, i.e., functio laesa.
Inflammation is also cogitated as one of the hallmarks of cancer. Chronic inflammation is known to plays a major role in the development of cancer. Inflammatory cells forming the tumor microenvironment can promote an increase in cell mass, and the ability of these cells to spread.,
Inflammation is part of the host response to either internal or external stimuli. Lymphocytes, plasma cells, and macrophages make a major part of chronic inflammation. The cells of chronic inflammation cause DNA damage by releasing cytokines, growth factors, reactive oxygen, and nitrogen species. Macrophages cause consistent tissue damage. A microenvironment constituted by all the above elements inhabits the sustained cell proliferation induced by continued tissue damage, thus predisposing chronic inflammation to neoplasia.
Like cancer of various origins, the development of OSCC is likewise linked with inflammation. Sustained tissue damage, damage-induced cellular proliferation, and tissue repair are characteristics of chronic inflammation. The proliferation and increase in the cellular count can be related to metaplasia which is a reversible change in the type of cell.
The pathomechanism of OSCC includes various inflammatory mediators such as nuclear factor kappa B, vascular endothelial growth factor (VEGF), cytokines, prostaglandins, p53, nitric oxide, reactive nitrogen species (RNS), reactive oxygen species (ROS), and some microRNAs.
Cordon-Cardo C and Prives C in their article mentioned the macrophage migration inhibitory factor which is known to overcome p53 functions by suppressing its transcriptional activity thus leading to tumor development.
Chronic inflammation alters the cellular levels of various inflammatory mediators. The hallmarks of cancer such as tumor promotion, survival, proliferation, invasion, angiogenesis, and metastasis are known to be associated with chronic inflammation and its mediators.,
Tumors need a new blood supply to survive and the inhibition of angiogenesis can inhibit tumor growth and metastasis causing, preformed tumors to necrose and regress. Chronic inflammation is closely associated with angiogenesis, as granulation tissue requires an extended vascular supply, and therefore, increases the bloody supply leading to tumor growth and promotion.
Inflammation and cancer are coupled by two pathways: extrinsic pathways from conditions that cause nonresolving heaving inflammatory responses, and intrinsic pathways driven by oncogenes or tumor suppressor genes that trigger the expression of inflammation-related programs.
| Types of Inflammation in Tumorigenesis|| |
The diverse types of inflammation which promote tumor promotion and survival can differ by etiology, mechanism, outcome, and intensity; these are:
Autoimmune disease or infections related
The infections are HTLV1, HPV, HCV, HBV, EBV, and Helicobacter pylori, and the autoimmune disease associated is mucosa-associated lymphoid tissue lymphomas.
These infections lead to the development of cancer through tumor promotion, better neoangiogenesis, oncogenic transmutations, and causing instability of the genomic structure.
Continuous contact with epigenetic/environmental factors
Tobacco smoke and inhaled silica/asbestos particles lead to lung cancer. Hepatocellular carcinoma develops due to chronic inflammation caused by obesity. Obesity increases the risk of cancer 1.6 times.
The solid tumor masses trigger an inflammatory response leading to the formation of the tumor-promoting environment. After a point, the central cells of the tumor mass become devoid of oxygen and nutrients leading to necrosis of these cells leading to the release of inflammatory mediators such as interleukin-1 and high-mobility group box proteins.
Cancer therapy-induced inflammation
The treatment of cancer which includes chemotherapy and radiotherapy causes trauma, necrosis, and injury to the tissues triggering an inflammatory response leading to further proliferation of tumor cells. However, therapy-induced inflammation can enhance the presentation of antigens and hence cancer obliteration.
| Cells Associated With Cancer-Related Inflammation|| |
Inflammatory cells secrete soluble factors that can contribute to the promotion of tumorigenesis by various mechanisms such as mutagenesis, cell proliferation and adaptation, angiogenesis, and inhibition of apoptosis.
Few inflammatory cells migrate to the tumor site and play a role in the establishment of tumor microenvironment. These are tumor-associated macrophages (TAMs), tumor-associated fibroblasts (TAFs), and a wide population of leukocytes and other types of immune cells. Macrophages, neutrophils, eosinophils, dendritic cells, mast cells, and lymphocytes are also found to be key components in carcinomas.
TAMs contribute to tumor development through several mechanisms. The antitumor responses are curbed by interleukin-10 and prostaglandin E2 which are released by TAMs. They release VEGF and endothelin 2 which further helps in angiogenesis. Furthermore, TAMs release matrix metalloproteinases (MMP), namely, MMP-2 and MMP-9 helping in tumor cell invasion and metastasis. TAMs may also induce tumor necrosis factor-alpha, inducible nitric oxide synthase, and produce epidermal growth factors. All the abovementioned factors aid in carcinogenesis.
TAFs are a major component of cancer-related inflammation and an important source of tumor-promoting cytokines and growth factors. They also provide physical support for tumor cells. The proliferation of TAF can indeed contribute to macrophage accumulation, in particular during type II inflammation. They facilitate extracellular matrix remodeling and promote angiogenesis.
Activated mast cells release angiogenic growth factors such as VEGF and fibroblast growth factor; angiogenic regulators such as histamine, heparin, matrix MMP-9, and mast cell-specific protease-4 and 6.,, These lead to increased angiogenesis and thus tumor promotion and sustainability.
Tumor-associated neutrophils enhance tumor angiogenesis, invasion, and metastasis analogous to TAMs and mast cells. Neutrophils may also play a role in the genetic instability of tumors.
| Biomarkers of Cancer-Related Inflammation|| |
A pivotal role of inflammatory cells in cancer progression has already been recognized in the literature. Numerous biomarkers have been proven to useful markers for cancer comportment.
They are proinflammatory cytokines such as interleukin 1 (IL 1) α, IL1 β, IL2, IL6, IL8, IL12, tumor necrosis factor-alpha, interferon-γ, CCL2, CXCL12, and VEGF. Other biomarkers include C-reactive protein, serum amyloid A ROS, RNS, prostaglandins, cyclooxygenases, and lipoxygenases.
For these biomarkers to show a definite result, the method of sample collection, storage, and transport should be accurate and precise. These inflammatory biomarkers can prove to be very useful in prognosis and diagnosis when the tumor is considered to be the major source of elevated cytokines in the blood of cancer patients.,
Inflammatory biomarkers can be used as a robust method of elucidating the association between inflammation and oral cancer.
| Conclusion|| |
“Reduce inflammation to treat the root of many issues.” – Jay Woodman.
Dysregulated inflammatory response is associated with most of the chronic diseases, including oral cancer. The identification of inflammatory molecules in oral cancer has proved their role in carcinogenesis. Inflammatory biomarkers could be used as prognostic indicators in oral cancer management. Newer and efficient anti-inflammatory drugs can be established for improved diagnosis and prognosis of oral carcinomas hence aiding in reducing the mortality associated with it.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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