• Users Online: 234
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
REVIEW ARTICLE
Year : 2022  |  Volume : 12  |  Issue : 2  |  Page : 46-49

Inflammation and oral cancer


Department of Oral Pathology and Microbiology, Faculty of Dental Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Date of Submission02-Apr-2022
Date of Decision02-Aug-2022
Date of Acceptance25-Aug-2022
Date of Web Publication19-Dec-2022

Correspondence Address:
Dr. Jaya Singh
Department of Oral Pathology and Microbiology, Faculty of Dental Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijohs.ijohs_8_22

Rights and Permissions
  Abstract 


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

How to cite this URL:
Singh J, Jain T, Agrawal R, Chandra A. Inflammation and oral cancer. Int J Oral Health Sci [serial online] 2022 [cited 2023 Feb 5];12:46-9. Available from: https://www.ijohsjournal.org/text.asp?2022/12/2/46/364231




  Introduction Top


Oral squamous cell carcinoma (OSCC) along with pharyngeal is the sixth-most common carcinoma in the world[1] and the third[2]-most common cancer in India. Two-thirds of OSCC occur in developing countries.[2] 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.[3] 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.[4] In men, it is the sixth-most common, and in women, the twelfth-most common carcinoma.[5] It has been propositioned in the past that the buccal mucosa can undergo malignant alterations.[6] Oral potentially malignant disorders have a high propensity to turn into malignancies such as OSCC.[7]

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.[8] 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).[9] 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.[10]

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.[9],[11]

Inflammation is part of the host response to either internal or external stimuli.[12] 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.[13]

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.[14] The proliferation and increase in the cellular count can be related to metaplasia which is a reversible change in the type of cell.[14]

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.[15]

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.[16]

Chronic inflammation alters the cellular levels of various inflammatory mediators.[15] 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.[14],[17]

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.[18]


  Types of Inflammation in Tumorigenesis Top


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.[19]

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.[20]

Tumor-associated inflammation

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.[21]

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.[19]


  Cells Associated With Cancer-Related Inflammation Top


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.[22] Macrophages, neutrophils, eosinophils, dendritic cells, mast cells, and lymphocytes are also found to be key components in carcinomas.[23]

TAMs contribute to tumor development through several mechanisms. The antitumor responses are curbed by interleukin-10 and prostaglandin E2 which are released by TAMs.[24] They release VEGF and endothelin 2 which further helps in angiogenesis.[25] Furthermore, TAMs release matrix metalloproteinases (MMP), namely, MMP-2 and MMP-9 helping in tumor cell invasion and metastasis.[26] TAMs may also induce tumor necrosis factor-alpha, inducible nitric oxide synthase, and produce epidermal growth factors.[23] 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.[27]

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.[28],[29],[30] 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.[31] Neutrophils may also play a role in the genetic instability of tumors.


  Biomarkers of Cancer-Related Inflammation Top


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.[18],[32]

Inflammatory biomarkers can be used as a robust method of elucidating the association between inflammation and oral cancer.


  Conclusion Top


“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

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 2009;45:309-16.  Back to cited text no. 1
    
2.
Birur P, Shubhasini AR, Bhanushree R, Mendonca P. Correlation of oral homogenous leukoplakia with grades of oral epithelial dysplasia. IOSR J Dent Med Sci 2014;12:98-103.  Back to cited text no. 2
    
3.
Sharma S, Satyanarayana L, Asthana S, Shivalingesh KK, Goutham BS, Ramachandra S. Oral cancer statistics in India on the basis of first report of 29 population-based cancer registries. J Oral Maxillofac Pathol 2018;22:18-26.  Back to cited text no. 3
[PUBMED]  [Full text]  
4.
Sankaranarayanan R, Ramadas K, Thomas G, Muwonge R, Thara S, Mathew B, et al. Effect of screening on oral cancer mortality in Kerala, India: A cluster-randomised controlled trial. Lancet 2005;365:1927-33.  Back to cited text no. 4
    
5.
Neville BW, Damm DD, Allen CR, Bouquot JE. Oral and Maxillofacial Pathology. 2nd ed. Philadelphia: WB Saunders; 2002. p. 316-376, 644-697.  Back to cited text no. 5
    
6.
Mortazavi H, Baharvand M, Mehdipour M. Oral potentially malignant disorders: An overview of more than 20 entities. J Dent Res Dent Clin Dent Prospects 2014;8:6-14.  Back to cited text no. 6
    
7.
Feller L, Lemmer J. Oral squamous cell carcinoma: Epidemiology, clinical presentation and treatment. J Cancer Ther 2012;3:263-8.  Back to cited text no. 7
    
8.
Punchard NA, Whelan CJ, Adcock I. The journal of inflammation. J Inflamm (Lond) 2004;1:1.  Back to cited text no. 8
    
9.
Gregory AD, Houghton AM. Tumor-associated neutrophils: New targets for cancer therapy. Cancer Res 2011;71:2411-6.  Back to cited text no. 9
    
10.
Hurley JV. Acute inflammation. Edinburgh, London: Churchill Livingstone; 2nd edition. 1972.  Back to cited text no. 10
    
11.
Mantovani A. Cancer: Inflaming metastasis. Nature 2009;457:36-7.  Back to cited text no. 11
    
12.
Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G. Inflammation and cancer: How hot is the link? Biochem Pharmacol 2006;72:1605-21.  Back to cited text no. 12
    
13.
Albini A, Sporn MB. The tumour microenvironment as a target for chemoprevention. Nat Rev Cancer 2007;7:139-47.  Back to cited text no. 13
    
14.
Singh N, Baby D, Rajguru JP, Patil PB, Thakkannavar SS, Pujari VB. Inflammation and cancer. Ann Afr Med 2019;18:121-6.  Back to cited text no. 14
[PUBMED]  [Full text]  
15.
Medzhitov R. Origin and physiological roles of inflammation. Nature 2008;454:428-35.  Back to cited text no. 15
    
16.
Cordon-Cardo C, Prives C. At the crossroads of inflammation and tumorigenesis. J Exp Med 1999;190:1367-70.  Back to cited text no. 16
    
17.
Patel JB, Shah FD, Joshi GM, Patel PS. Clinical significance of inflammatory mediators in the pathogenesis of oral cancer. J Cancer Res Ther 2016;12:447-57.  Back to cited text no. 17
    
18.
Balkwill FR, Mantovani A. Cancer-related inflammation: Common themes and therapeutic opportunities. Semin Cancer Biol 2012;22:33-40.  Back to cited text no. 18
    
19.
Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010;140:883-99.  Back to cited text no. 19
    
20.
Calle EE. Obesity and cancer. BMJ 2007;335:1107-8.  Back to cited text no. 20
    
21.
Rock KL, Kono H. The inflammatory response to cell death. Annu Rev Pathol 2008;3:99-126.  Back to cited text no. 21
    
22.
Yang CR, Hsieh SL, Ho FM, Lin WW. Decoy receptor 3 increases monocyte adhesion to endothelial cells via NF-κB-dependent up-regulation of intercellular adhesion molecule-1, VCAM-1, and IL-8 expression. J Immunol 2005;174:1647-56.  Back to cited text no. 22
    
23.
Lu H, Ouyang W, Huang C. Inflammation, a key event in cancer development. Mol Cancer Res 2006;4:221-33.  Back to cited text no. 23
    
24.
Elgert KD, Alleva DG, Mullins DW. Tumor-induced immune dysfunction: The macrophage connection. J Leukoc Biol 1998;64:275-90.  Back to cited text no. 24
    
25.
Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 2004;4:71-8.  Back to cited text no. 25
    
26.
Coussens LM, Raymond WW, Bergers G, Laig-Webster M, Behrendtsen O, Werb Z, et al. Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis. Genes Dev 1999;13:1382-97.  Back to cited text no. 26
    
27.
Monteran L, Erez N. The dark side of fibroblasts: Cancer-associated fibroblasts as mediators of immunosuppression in the tumor microenvironment. Front Immunol 2019;10:1835.  Back to cited text no. 27
    
28.
Lin EY, Pollard JW. Role of infiltrated leucocytes in tumour growth and spread. Br J Cancer 2004;90:2053-8.  Back to cited text no. 28
    
29.
Ribatti D, Vacca A, Nico B, Crivellato E, Roncali L, Dammacco F. The role of mast cells in tumour angiogenesis. Br J Haematol 2001;115:514-21.  Back to cited text no. 29
    
30.
Hiromatsu Y, Toda S. Mast cells and angiogenesis. Microsc Res Tech 2003;60:64-9.  Back to cited text no. 30
    
31.
Masucci MT, Minopoli M, Carriero MV. Tumor associated neutrophils. Their role in tumorigenesis, metastasis, prognosis and therapy. Front Oncol 2019;9:1146.  Back to cited text no. 31
    
32.
Epstein JB, Zhang L, Rosin M. Advances in the diagnosis of oral premalignant and malignant lesions. J Can Dent Assoc 2002;68:617-21.  Back to cited text no. 32
    




 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
   Abstract
  Introduction
   Types of Inflamm...
   Cells Associated...
   Biomarkers of Ca...
  Conclusion
   References

 Article Access Statistics
    Viewed308    
    Printed18    
    Emailed0    
    PDF Downloaded39    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]