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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
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2155-8213.128104

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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 2023 May 30];5:3-6. Available from:

  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

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