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MINI REVIEW
Year : 2014  |  Volume : 5  |  Issue : 1  |  Page : 3-6

Helicobacter pylori-possible role as biomarker for oral cancer


1 Department of Oral Pathology and Microbiology, DPUs, Dr. Dnyandeo Yashwantrao Patil Dental College and Hospital, Pune, Maharashtra, India
2 Department of Prosthodontics and Oral Implantology, Rangoonwala College of Dental Sciences and Research Centre, Pune, Maharashtra, India

Date of Web Publication3-Mar-2014

Correspondence Address:
Supriya M Kheur
Department of Oral Pathology and Microbiology, DPUs, Dr. Dnyandeo Yashwantrao Patil Dental College and Hospital, Pune - 411 018, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2155-8213.128104

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  Abstract 

Oral cancer is the most common cancer diagnosed in Indian men and is the leading cause of cancer deaths. Amongst other causes infections with Helicobacter pylori is an emerging cause of oral squamous cell carcinoma. There is still confusion in the route of transmission and the exact etiopathogenesis of H. pylori associated oral cancer. Knowledge of the microbiology and immunology of H. pylori is important to prevent its spread and may be useful in identifying high-risk populations, especially in areas that have high rates of gastric lymphoma, gastric cancer, and gastric ulcer. This paper presents an overview of the important aspects of H. pylori.

Keywords: Etiopathogenesis, Helicobacter pylori, immunology, oral cancer


How to cite this article:
Gupta AA, Kheur SM, Kheur M, Saner SR. Helicobacter pylori-possible role as biomarker for oral cancer. Dent Hypotheses 2014;5:3-6

How to cite this URL:
Gupta AA, Kheur SM, Kheur M, Saner SR. Helicobacter pylori-possible role as biomarker for oral cancer. Dent Hypotheses [serial online] 2014 [cited 2019 May 23];5:3-6. Available from: http://www.dentalhypotheses.com/text.asp?2014/5/1/3/128104


  Introduction Top


Oral cancer has become the leading cause of morbidity and mortality and accounts for 10%-20% of deaths. [1] The most common oral manifestations are white or red patches in mouth, among healing ulcer, bleeding in mouth, loose teeth, dysphagia, a lump in neck, an earache. Surgery is generally the first line of treatment, which along with curing the disease also causes morbidity, deteriorating the quality of life. Treatment also includes spiritual and psychosocial support both to the patient and their families. [2] Identifying higher risk groups and early detection of the disease requires a deep understanding of the etiology of disease. [3],[4]

Established risk factors of oral cancer include poor oral hygiene, tobacco in the form of smoking and chewing, gutkha and areca nut. [5] However, cases of oral cancer have also been reported even in absence of such habits. These, if not primary, can act as cofactors to the tobacco and areca nut in developing an oral cancer. Literature review suggests that these factors can be of microbial origin, both bacterial and viral, psychosomatic, chronic irritations. Among various infectious agents, human papillomavirus, Candida, and Helicobacter pylori have been investigated. [4],[5]

H. pylori infection is considered as one of the most prevalent infectious diseases throughout the world; the carriage rate of H. pylori is reported to be 20%-80% for adults in the developed world, and more than 90% in the developing world. [6] This infection generally causes peptic ulcers [7],[8] and is associated with gastric cancer. [9],[10] After the discovery of this association, the recurrence rate of peptic ulcers, which was 80% formerly, has declined to 20%. [11] Production of ROS leading to oxidative DNA damage and release of MMP-8 leading to accelerated proteolysis has been associated with the bacteria. [12],[13] Newer studies are correlating the presence of these bacteria to a state of persistent chronic inflammation and subsequent oral carcinoma. Early detection and eradication of this bacterium would be helpful in the prevention of periodontitis and oral cancer, thereby reducing the economical burden imposed to the health systems by the disease.


  H. pylori Microbiological Aspects Top


The spiral, microaerophilic, gram-negative bacteria assume a rod-like shape when cultured on solid medium and coccoid forms on prolonged culturing. [14] It measures approximately 3.5 microns in length and 0.5 microns in width [Figure 1]. The organisms are 2.5-5.0 mm long and 0.5-1.0 mm wide containing flagella which is required for the motility of the organism. [15] This slow-growing organism can be cultured on blood agar or selective media such as Skirrow's media incubated at 37°C in a 5 percent oxygen atmosphere for 3-7 days. [16] Morphologically, the organisms can be characterized by gram stain. [15] Coccoid forms of bacteria are more resistant to hostile environment and can survive in feces or in drinking water. [17]
Figure 1: The rod shaped H. pylori seen in the gastric mucosa section

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Biochemically, bacteria can be characterized as catalase, oxidase, and urease positive, which appear to be vital for its survival and colonization. [16] It also forms the basis for several invasive and noninvasive tests to diagnose infection. [17]


  H. pylori Immunological Aspects Top


This gram-negative bacterium has been identified with four virulence factors namely, cytotoxin-associated antigen A (CagA), cag-pathogenicity island (cagPAI), vacuolatingcytotoxin (VacA), and outer membrane proteins (OMPs). [18],[19] CagA protein and peptidoglycan (PGN) are delivered into host cells with the help of type four secretion system (TFSS), encoded by cagPAI. [20] Various intracellular pathways are activated owing to the entry of bacterial virulence factors, which further leads to oncogenic transformation [21] of epithelial cells [Figure 2]. [22],[23]
Figure 2: Pathogenesis how H. pylori leads to oncogenic cell transformation

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Bacterial oncoprotein CagA induces multiple malignancies, [24] including gastric epithelial hyperplasia, hyperplastic polyps, gastrointestinal carcinomas, and hematological malignancies. [25]


  H. pylori Association with Persistent Chronic Inflammation Top


Inflammation is a complex defence mechanism including migration of leukocytes from venous system to damaged site. [26] Neutrophils is the first to invade the site releasing cytokines which help in their adhesion to vascular endothelium, restricting the leukocytes to the area of repair. [27],[28] After this macrophages invade the area and the neutrophils progressively decline owing to their phagocytosis by the macrophages. [29],[30] Once activated macrophages act as main source of growth factors and cytokines following which mast cells come into existence. After their activation by complement, they degranulate and release various mediators required for tissue healing. [26] H. pylori as infectious agent and chronic inflammation as noninfectious agent, leading to gastric and pancreatic cancer [31],[26] serve as the best examples of infection and inflammation leading to cancerous growth. Periodontal pocketing and inflammation helps in colonization of this species in urease rich subgingival biofilm which also serves as selective ecological niche for the urease producing bacteria helping it in recolonization and reinfection in gastric mucosa. [32],[33],[34]


  H. pylori and Role in Alteration in Gastrointestinal Mucosa Top


H. pylori is associated with inflammatory cytokine production including interleukin (IL)-1β, tumor necrosis factor-α, and IL-10, [35],[36],[37] disrupting gastric homeostasis. IL-1 β inhibits gastric acid secretion and induces inflammation, metaplasia, dysplasia, and finally carcinoma. H. pylori invade epithelial cells and their progenitors and disrupt their differentiation by introducing molecular damage in cells. [38]

Chronic inflammation associated with H. pylori induces increased infiltration of immune cells, (neutrophils, macrophages, and T and B lymphocytes) in gastric mucosa. An alternative source of tumor-initiating cells, recruit bone marrow derived cells (BMDCs) to the inflammatory site in chronic inflammation. [39] BMDCs can differentiate into cells of diverse lineages including myofibroblasts, epithelial cells, or cancer-associated fibroblasts promoting tumor growth. [40]


  Proposed Role of H. pylori in Oral Cancer Top


Possible association of H. pylori with oral cancer has been suggested by several investigators.

Fernando et al., [41] in 2009 reviewed that people with gum disease are more likely to test positive for H. pylori. They also concluded with their study on Sri Lankan population that betel chewing may predispose to colonization with H. pylori in digestive tract through swallowing the quid or during betel chewing.

Panahi et al., [42] in 2011 in his study indicated that H. pylori is present in dental plaque, although the number of organisms in individual samples is very low, and these numbers appear to vary from one site to another within the mouth. The presence of this organism in plaque may be fitful, perhaps occurring as the result of gastroesophageal reflux.

Dayama et al., [43] in 2011 carried out a hospital-based, case-control study of 20 patients with newly diagnosed oral cancer and 20 healthy controls without any cancer to evaluate associations between H. pylori infection and oral cancer using culture and 16sRNA polymerase chain reaction (PCR) technique for bacterial identification. H. pylori was isolated from the culture of three cases and one control, while three cases and two controls showed PCR positivity for H. pylori 16sRNA. However, the results of this pilot study suggest a possible association of H. pylori with an increased risk of oral cancer. However, additional studies in larger populations were recommended to confirm and to quantify this possible association more accurately.


  Conclusion Top


H. pylori is a microorganism that causes or is associated with a curable chronic infection. Earlier, it was considered to be a part of dental plaque, as its ecological niche. Now, newer reports are showing an increase in H. pylori in patients with oral cancer, pointing toward a probable causative role in development of oral cancer. It is early to postulate a definitive role and further studies are required to validate the role H. pylori in its cancer development.

 
  References Top

1.Petersen PE. Oral cancer prevention and control - the approach of the world health organization. Oral Oncol 2009;45:454-60.  Back to cited text no. 1
    
2.World Health Organization. National Cancer Control Programmes: Policies and managerial guidelines: Executive summary. Geneva: WHO; 2002.  Back to cited text no. 2
    
3.American Cancer Society. Cancer Facts & Figures 2013. American Cancer Society, Inc., Atlanta, GA, 2013.  Back to cited text no. 3
    
4.Michaud DS. Role of bacterial infections in pancreatic cancer. Carcinog 2013;34:2193-7.  Back to cited text no. 4
    
5.Lynch SM. Vrieling A, Lubin JH, Kraft P, Mendelsohn JB, Hartge P, et al. Cigarette smoking and pancreatic cancer: A pooled analysis from the pancreatic cancer cohort consortium. Am J Epidemiol 2009;170:403-13.  Back to cited text no. 5
    
6.Taylor DN, Blaser MJ. The epidemiology of Helicobacter pylori infection. Epidemiol Rev 1991;13:42-59.  Back to cited text no. 6
    
7.Lee A, Fox J, Hazell S. Pathogenecity of Helicobacter pylori: A perspective. Infect Immun 1993;61:1601-10.  Back to cited text no. 7
    
8.Dixon MF. Helicobacter Pylori and peptic ulceration: Histopathological aspects. J Gastroenetrol Hepatol 1991;6:125-30.  Back to cited text no. 8
    
9.Forman D, Newell DG, Fullerton F, Yarnell JW, Stacey AR, Wald N, et al. Association between infection with Helicobacter pylori and risk of gastric cancer: Evidence from a prospective investigation. BMJ 1991;302:1302-5.  Back to cited text no. 9
    
10.Parsonnet J, Vandersteen D, Goates J, Sibley RK, Pritikin J, Chang Y. Helicobacter pylori infection in intestinal- and diffuse-type gastric adenocarcinomas. J Natl Cancer Inst 1991;83:640-5.  Back to cited text no. 10
    
11.Kilmartin CM. Dental implications of Helicobacter pylori. J Can Dent Assoc 2002;68:489-93.  Back to cited text no. 11
    
12.Arinati F, Cardin R, Cassaro M, Bortolami M, Nitti D, Tieppo C, et al. Helicobacter pylori, inflammation, oxidative damage and gastric cancer: A morphological, biological and molecular pathway. Eur J Cancer Prev. 2008;17:195-200.  Back to cited text no. 12
    
13.Rautelin HI, Oksanen AM, Veijola LI, Sipponen PI, Tervahartiala TI, Sorsa TA, et al. Enhanced systemic matrix metalloproteinase response in Helicobacter pylori gastritis. Ann Med. 2009;41:208-15.  Back to cited text no. 13
    
14.Akamatsu T, Tabata K, Hironga M, Kawakami H, Uyeda M. Transmission of Helicobacter pylori infection via flexible fiberoptic endoscopy. Am J Infect Control 1996;24:396-401.  Back to cited text no. 14
    
15.Dunn BE, Cohen H, Blaser MJ. Helicobacter pylori. Clin Microbiol Rev 1997;10:720-41.  Back to cited text no. 15
    
16.Goodwin CS, Worsley BW. Microbiology of Helicobacter pylori. Gastroenterol Clin North Am 1993;22:5-19.  Back to cited text no. 16
    
17.Medina ML, Medina MG, Martín GT, Picón SO, Bancalari A, Merino LA. Molecular detection of Helicobacter pylori in oral samples from patients suffering digestive pathologies. Med Oral Patol Oral Cir Bucal 2010;15:38-42.  Back to cited text no. 17
    
18.Segal ED, Cha J, Lo J, Falkow S, Tompkins LS. Altered states: Involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori. Proc Natl Acad Sci USA 1999;96:14559-64.  Back to cited text no. 18
    
19.Viala J, Chaput C, Boneca IG, Cardona A, Girardin SE, Moran AP, et al. Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat Immunol 2004;5:1166-74.  Back to cited text no. 19
    
20.Hatakeyama M. Linking epithelial polarity and carcinogenesis by multitasking Helicobacter pylori virulence factor CagA. Oncogene 2008;27:7047-54.  Back to cited text no. 20
    
21.Radin JN, Gonzalez-Rivera C, Ivie SE, McClain MS, Cover TL. Helicobacter pylori VacA induces programmed necrosis in gastric epithelial cells. Infect Immun 2011;79:2535-43.  Back to cited text no. 21
    
22.Ernst PB, Peura DA, Crowe SE. The translation of Helicobacter pylori basic research to patient care. Gastroenterol 2006;130:188-206.  Back to cited text no. 22
    
23.Ding SZ, Goldberg JB, Hatakeyama M. Helicobacter pylori infection, oncogenic pathways and epigenetic mechanisms in gastric carcinogenesis. Future Oncol 2010;6:851-62.  Back to cited text no. 23
    
24.Ohnishi N, Yuasa H, Tanaka S, Sawa H, Miura M, Matsui A, et al. Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc Natl Acad Sci USA 2008;105:1003-8.  Back to cited text no. 24
    
25.Ding SZ, Zheng PY. Helicobacter pylori infection induced gastric cancer; advance in gastric stem cell research and the remaining challenges. Gut Pathog 2012;4:18.  Back to cited text no. 25
    
26.Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420:860-7.  Back to cited text no. 26
    
27.Feiken E, Romer J, Eriksen J, Lund LR. Neutrophils express tumor necrosis factor-alpha during mouse skin wound healing. J Invest Dermatol 1995;105:120-3.  Back to cited text no. 27
    
28.Chedid M, Rubin JS, Csaky KG, Aaronson SA. Regulation of keratinocyte growth factor gene expression by interleukin 1. J Biol Chem 1994;269:10753-7.  Back to cited text no. 28
    
29.Eming SA, Krieg T, Davidson JM. Inflammation in wound repair: Molecular and cellular mechanisms. J Invest Dermatol 2007;127:514-25.  Back to cited text no. 29
    
30.Osusky R, Malik P, Ryan SJ. Retinal pigment epithelium cells promote the maturation of monocytes to macrophages in vitro. Ophthalmic Res 1997;29:31-6.  Back to cited text no. 30
    
31.Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet 2001;357:539-45.  Back to cited text no. 31
    
32.Gebara EC, Pannuti C, Faria CM, Chehter L, Mayer MP, Lima LA. Prevalence of Helicobacter pylori detected by polymerase chain reaction in the oral cavity of periodontitis patients. Oral Microbiol Immunol 2004;19:277-80.   Back to cited text no. 32
    
33.Riggio MP, Lennon A. Identification by PCR of Helicobacter pylori in subgingival plaque of adult periodontitis patients. J Med Microbiol 1999;48:317-22.   Back to cited text no. 33
    
34.Umeda M, Kobayashi H, Takeuchi Y, Hayashi J, Morotome-Hayashi Y, Yano K, et al. High prevalence of Helicobacter pylori detected by PCR in the oral cavities of periodontitis patients. J Periodontol 2003;74:129-34.   Back to cited text no. 34
    
35.Tu S, Bhagat G, Cui G, Takaishi S, Kurt-Jones EA, Rickman B, et al. Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell 2008;14:408-19.  Back to cited text no. 35
    
36.Tu SP, Quante M, Bhagat G, Takaishi S, Cui G, Yang XD, et al. IFN-y inhibits gastric carcinogenesis by inducing epithelial cell autophagy and T-cellapoptosis. Cancer Res 2011;71:4247-59.  Back to cited text no. 36
    
37.El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 2000;404:398-402.  Back to cited text no. 37
    
38.Necchi V, Candusso ME, Tava F, Luinetti O, Ventura U, Fiocca R, et al. Intracellular, intercellular, and stromal invasion of gastric mucosa, preneoplastic lesions, and cancer by Helicobacter pylori. Gastroenterol 2007;132:1009-23.  Back to cited text no. 38
    
39.Okumura T, Wang SS, Takaishi S, Tu SP, Ng V, Ericksen RE, et al. Identification of a bone marrow-derived mesenchymal progenitor cell subset that can contribute to the gastric epithelium. Lab Invest 2009;89:1410-22.  Back to cited text no. 39
    
40.Gonda TA, Tu S, Wang TC. Chronic inflammation, the tumor microenvironment and carcinogenesis. Cell Cycle 2009;8:2005-13.  Back to cited text no. 40
    
41.Fernando N, Jayakumar G, Perera N, Amarasingha I, Meedin F, Holton J. Presence of Helicobacter pylori in betel chewers and non betel chewers with and without oral cancers. BMC Oral Health 2009;9:23.  Back to cited text no. 41
    
42.Panahi O, Rezaei S, Marzi M, Asghari FS. Helicobacter pylori and oral cavity inflammation. JPCS 2011;2:13-5.  Back to cited text no. 42
    
43.Dayama A, Srivastava V, Shukla M, Singh R, Pandey M. Helicobacter pylori and oral cancer: Possible association in apreliminary case control study. Asian Pac J Cancer Prev 2011;12:1333-6.  Back to cited text no. 43
    


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