Oral Oncology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
Letter to the Editor Oral prophylaxis as an adjunct procedure towards prevention and management of oral cancer: Rationale and application
Oral cancer is the most common cancer diagnosed in Indian men and is the leading cause of cancer deaths [1]. Although it possesses a multifactorial etiology, besides conventional risk factors already described in literature (tobacco and alcohol consumption) other emerging risk factors, such as microbiological and inflammatory factors have been recently proposed [2,3]. Of particular interest is the rise in the literature of reports on cases of oral cancer in individuals who do not consume tobacco in any form [4]. H.pylori in 1994, after many clinical studies became the first species of bacteria to be classified by World Health Organisation for Research on Cancer(IARC) as a definitive cause of cancer (Class-I carcinogen) [5]. Since then, many other micro-organisms like Chlamydia trachomatis, Streptococcus bovis, Salmonella typhae has been shown to be associated with cervical cancer, colonic cancer and carcinoma of gall bladder [5]. The mouth comprises of a variety of different surfaces that are home to a huge diversity of microorganisms, including more than 750 distinct taxa of bacteria. The oral epithelium is thus constantly exposed to a variety of microbial challenges, on both cellular and molecular levels. Jenkinson and Lamont [6] has reported the progression of OSMF like diseases to oral cancer owing to persistent chronic inflammation and poor oral hygiene status of individuals [7]. This points to the association of increased local bacterial load and progression to oral cancer. A direct link between periodontal bacteria and oral cancer has not been firmly established. The mechanism, of how bacteria are linked to oral cancer (extrinsic pathway) could be the same as the inflammation caused by invading malignant cells (intrinsic pathway). This extrinsic pathway from pre existing inflammatory conditions may favour the onset of cancer [8]. Feller et al. in 2013 suggested that the transcription factors that have been once activated have the capacity to enhance expression of genes that are common to both the regulation and the production of the mediators of inflammation, and also to the regulation of the survival and proliferation of cancer cells [9]. A vast number of organisms have been proposed to be associated with periodontitis including P. gingivalis, P. intermedia, Bacteroides forsythus, A. actinomycetemcomitans [10]. Porphyromonas gingivalis can induce COX-2 expression [11] and increase the levels of proinflammatory mediators such as TNF- a, IL-6, IL-8 & IL-1b [12]. Eikenella corrodens can also stimulate epithelial cells to produce IL-6, IL-8 and PGE2 [13]. One preliminary study, in the literature has indicated an association between periodontal disease and the presence of precancerous and neoplastic oral lesions. In an analysis of 13,798 subjects aged 20 years and older, clinical attachment loss was http://dx.doi.org/10.1016/j.oraloncology.2014.05.001 1368-8375/Ó 2014 Elsevier Ltd. All rights reserved.
measured as a representation of the severity of periodontal disease and compared against 3 separate variables: the presence or absence of a tumor, a precancerous lesion, or another soft-tissue lesion in the oral cavity. Descriptive statistics suggested associations between periodontal disease and the risk for precancerous lesions and tumors [14]. In most of the cases of oral carcinoma studied in our department in the past two years, we have found chronic periodontitis in 85% of the cases with loss of attachment. Tooth ache and mobility are early features prompting the patients to discontinue tooth brushing, thereby starting a downward escalation of oral hygiene. Thus, when the patient approaches the tertiary or secondary diagnostic centers, extraction of the offended teeth are done generally due to the primary complain of tooth ache. This leads to early local metastasis. The periodontal condition worsens further with an increased local bacterial load. These periodontal infections are further related to generalized bacteremia and systemic diseases. Evaluation of viruses and candida as adjunct to oral cancer has already been reported [15,16]. Similarly, bacterial etiology is also important and periodontal microflora needs a specific mention in the same. Thus, a novel pilot research project started in our department is that all patients diagnosed with Potentially Malignant Disorders are subjected to thorough oral prophylaxis along with counseling for discontinuation of habit and prescribing antioxidants. The preliminary results of this protocol are very encouraging. A long term longitudinal study will only reveal whether this procedure will prove to be a beneficial step in reducing the incidence of oral cancer by reducing the bacterial load and local inflammation. This could lead to addition of oral prophylaxis as a standard oral cancer management protocol. Conflict of interest statement None. Financial disclosure No assistance was taken from any agency. References [1] Petersen PE. Oral cancer prevention and control – The approach of the World Health Organization. Oral Oncol 2009;45(4–5):454–6. [2] Gapstur SM, Gann PH, Lowe W, et al. Abnormal glucose metabolism and pancreatic cancer mortality. JAMA 2000;283:2552–8. [3] Stolzenberg-Solomon RZ, Graubard BI, Chari S, et al. Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers. JAMA 2005;294:2872–8. [4] Dayama A, Srivastava V, Shukla M, et al. Helicobacter pylori and oral cancer: possible association in a preliminary case control study. Asian Pacific J Cancer Prev 2011;12:1333–6.
2
Letter to the Editor / Oral Oncology xxx (2014) xxx–xxx
[5] Hooper SJ, Wilson MJ, Crean StJ. Exploring the link between microorganisms and oral cancer: a systematic review of literature. Head Neck 2009;31(9):1228–39. [6] Jenkinson HF, Lamont RJ. Oral microbial communities in sickness and in health. Trends Microbiol 2005;13:589–95. [7] Satheeshkumar PS, Mohan MP. Malignant potential of oral submucous fibrosis due to intraoral extraction wounds and poor oral hygiene. Oral Oncol 2014;50(1):e5–6. [8] Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008;454(7203):436–44. [9] Feller L, Altini M, Lemmer J. Inflammation in the context of oral cancer. Oral Oncol 2013;49:887–92. [10] Feng Z, Weinberg A. Role of bacteria in health and disease of periodontal tissues. Periodontology 2000 2006;40:50–76. [11] Kuramitsu HK, Miyakawa H, Qi M, Kang IC. Cellular responses to oral pathogens. Ann Periodontol 2002;7:90–4. [12] Andrian E, Grenier D, Rouabhia M. In vitro models of tissue penetration and destruction by Porphyromonasgingivalis. Infect Immun 2004;72:4689–98. [13] Yumoto H, Nakae H, Yamada M, et al. Soluble products from Eikenellacorrodens stimulate oral epithelial cells to induce inflammatory mediators. Oral Microbiol Immunol 2001;16:296–305. [14] Tezal M, Grossi SG, Genco RJ. Is periodontitis associated with oral neoplasms? J Periodontol 2005;76:406–10. [15] Sanjaya PR, Gokul S, Patil GB, et al. Candida in oral pre-cancer and oral cancer. Med Hypotheses 2011;77:1125–8. [16] Gonzalez-Moles MA, Gutierrez J, Rodriguez MJ, et al. Epstein–Barr virus latent membrane protein-1 (LMP-1) expression in oral squamous cell carcinoma. Laryngoscope 2002;112:482–7.
Supriya M. Kheur Professor and Head, Department of Oral Pathology and Microbiology, DPUs, Dr. D. Y. Patil Dental College and Hospital, Pune, India Tel.: +91 9970150760. E-mail address: [email protected] Mohit Kheur Professor, Department of Maxillofacial Rehabilitation, Rangoonwala College of Dental Sciences, Pune, India E-mail address: [email protected] Archana A. Gupta Post Graduate Student, Department of Oral Pathology and Microbiology, DPUs, Dr. D. Y. Patil Dental College and Hospital, Pune, India E-mail address: [email protected] Available online xxxx
Contents lists available at ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
Letter to the Editor Oral prophylaxis as an adjunct procedure towards prevention and management of oral cancer: Rationale and application
Oral cancer is the most common cancer diagnosed in Indian men and is the leading cause of cancer deaths [1]. Although it possesses a multifactorial etiology, besides conventional risk factors already described in literature (tobacco and alcohol consumption) other emerging risk factors, such as microbiological and inflammatory factors have been recently proposed [2,3]. Of particular interest is the rise in the literature of reports on cases of oral cancer in individuals who do not consume tobacco in any form [4]. H.pylori in 1994, after many clinical studies became the first species of bacteria to be classified by World Health Organisation for Research on Cancer(IARC) as a definitive cause of cancer (Class-I carcinogen) [5]. Since then, many other micro-organisms like Chlamydia trachomatis, Streptococcus bovis, Salmonella typhae has been shown to be associated with cervical cancer, colonic cancer and carcinoma of gall bladder [5]. The mouth comprises of a variety of different surfaces that are home to a huge diversity of microorganisms, including more than 750 distinct taxa of bacteria. The oral epithelium is thus constantly exposed to a variety of microbial challenges, on both cellular and molecular levels. Jenkinson and Lamont [6] has reported the progression of OSMF like diseases to oral cancer owing to persistent chronic inflammation and poor oral hygiene status of individuals [7]. This points to the association of increased local bacterial load and progression to oral cancer. A direct link between periodontal bacteria and oral cancer has not been firmly established. The mechanism, of how bacteria are linked to oral cancer (extrinsic pathway) could be the same as the inflammation caused by invading malignant cells (intrinsic pathway). This extrinsic pathway from pre existing inflammatory conditions may favour the onset of cancer [8]. Feller et al. in 2013 suggested that the transcription factors that have been once activated have the capacity to enhance expression of genes that are common to both the regulation and the production of the mediators of inflammation, and also to the regulation of the survival and proliferation of cancer cells [9]. A vast number of organisms have been proposed to be associated with periodontitis including P. gingivalis, P. intermedia, Bacteroides forsythus, A. actinomycetemcomitans [10]. Porphyromonas gingivalis can induce COX-2 expression [11] and increase the levels of proinflammatory mediators such as TNF- a, IL-6, IL-8 & IL-1b [12]. Eikenella corrodens can also stimulate epithelial cells to produce IL-6, IL-8 and PGE2 [13]. One preliminary study, in the literature has indicated an association between periodontal disease and the presence of precancerous and neoplastic oral lesions. In an analysis of 13,798 subjects aged 20 years and older, clinical attachment loss was http://dx.doi.org/10.1016/j.oraloncology.2014.05.001 1368-8375/Ó 2014 Elsevier Ltd. All rights reserved.
measured as a representation of the severity of periodontal disease and compared against 3 separate variables: the presence or absence of a tumor, a precancerous lesion, or another soft-tissue lesion in the oral cavity. Descriptive statistics suggested associations between periodontal disease and the risk for precancerous lesions and tumors [14]. In most of the cases of oral carcinoma studied in our department in the past two years, we have found chronic periodontitis in 85% of the cases with loss of attachment. Tooth ache and mobility are early features prompting the patients to discontinue tooth brushing, thereby starting a downward escalation of oral hygiene. Thus, when the patient approaches the tertiary or secondary diagnostic centers, extraction of the offended teeth are done generally due to the primary complain of tooth ache. This leads to early local metastasis. The periodontal condition worsens further with an increased local bacterial load. These periodontal infections are further related to generalized bacteremia and systemic diseases. Evaluation of viruses and candida as adjunct to oral cancer has already been reported [15,16]. Similarly, bacterial etiology is also important and periodontal microflora needs a specific mention in the same. Thus, a novel pilot research project started in our department is that all patients diagnosed with Potentially Malignant Disorders are subjected to thorough oral prophylaxis along with counseling for discontinuation of habit and prescribing antioxidants. The preliminary results of this protocol are very encouraging. A long term longitudinal study will only reveal whether this procedure will prove to be a beneficial step in reducing the incidence of oral cancer by reducing the bacterial load and local inflammation. This could lead to addition of oral prophylaxis as a standard oral cancer management protocol. Conflict of interest statement None. Financial disclosure No assistance was taken from any agency. References [1] Petersen PE. Oral cancer prevention and control – The approach of the World Health Organization. Oral Oncol 2009;45(4–5):454–6. [2] Gapstur SM, Gann PH, Lowe W, et al. Abnormal glucose metabolism and pancreatic cancer mortality. JAMA 2000;283:2552–8. [3] Stolzenberg-Solomon RZ, Graubard BI, Chari S, et al. Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers. JAMA 2005;294:2872–8. [4] Dayama A, Srivastava V, Shukla M, et al. Helicobacter pylori and oral cancer: possible association in a preliminary case control study. Asian Pacific J Cancer Prev 2011;12:1333–6.
2
Letter to the Editor / Oral Oncology xxx (2014) xxx–xxx
[5] Hooper SJ, Wilson MJ, Crean StJ. Exploring the link between microorganisms and oral cancer: a systematic review of literature. Head Neck 2009;31(9):1228–39. [6] Jenkinson HF, Lamont RJ. Oral microbial communities in sickness and in health. Trends Microbiol 2005;13:589–95. [7] Satheeshkumar PS, Mohan MP. Malignant potential of oral submucous fibrosis due to intraoral extraction wounds and poor oral hygiene. Oral Oncol 2014;50(1):e5–6. [8] Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008;454(7203):436–44. [9] Feller L, Altini M, Lemmer J. Inflammation in the context of oral cancer. Oral Oncol 2013;49:887–92. [10] Feng Z, Weinberg A. Role of bacteria in health and disease of periodontal tissues. Periodontology 2000 2006;40:50–76. [11] Kuramitsu HK, Miyakawa H, Qi M, Kang IC. Cellular responses to oral pathogens. Ann Periodontol 2002;7:90–4. [12] Andrian E, Grenier D, Rouabhia M. In vitro models of tissue penetration and destruction by Porphyromonasgingivalis. Infect Immun 2004;72:4689–98. [13] Yumoto H, Nakae H, Yamada M, et al. Soluble products from Eikenellacorrodens stimulate oral epithelial cells to induce inflammatory mediators. Oral Microbiol Immunol 2001;16:296–305. [14] Tezal M, Grossi SG, Genco RJ. Is periodontitis associated with oral neoplasms? J Periodontol 2005;76:406–10. [15] Sanjaya PR, Gokul S, Patil GB, et al. Candida in oral pre-cancer and oral cancer. Med Hypotheses 2011;77:1125–8. [16] Gonzalez-Moles MA, Gutierrez J, Rodriguez MJ, et al. Epstein–Barr virus latent membrane protein-1 (LMP-1) expression in oral squamous cell carcinoma. Laryngoscope 2002;112:482–7.
Supriya M. Kheur Professor and Head, Department of Oral Pathology and Microbiology, DPUs, Dr. D. Y. Patil Dental College and Hospital, Pune, India Tel.: +91 9970150760. E-mail address: [email protected] Mohit Kheur Professor, Department of Maxillofacial Rehabilitation, Rangoonwala College of Dental Sciences, Pune, India E-mail address: [email protected] Archana A. Gupta Post Graduate Student, Department of Oral Pathology and Microbiology, DPUs, Dr. D. Y. Patil Dental College and Hospital, Pune, India E-mail address: [email protected] Available online xxxx
