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

 Table of Contents  
Year : 2016  |  Volume : 6  |  Issue : 2  |  Page : 102-107

Viruses: Role in oral squamous cell carcinoma and oral precancerous lesions

Department of Oral Medicine and Radiology, CSMSS Dental College and Hospital, Aurangabad, Maharashtra, India

Date of Web Publication3-May-2016

Correspondence Address:
Ashwini Sudhakar Jadhav
23, Kastur Kunj, Sharada Colony, Beside Dewang Hostel, Pimple Nilakh, Pune - 411 027, Maharashtra
Login to access the Email id

DOI: 10.4103/2249-9725.181684

Rights and Permissions

Oral cancers and precancerous lesions are the most common diseases of concern in the world. These conditions have a high mortality rate which is rapidly increasing. Although various factors like tobacco consumption, alcohol, genetics, etc., play a role in etiopathogenesis of these lesions, currently there is a lot of growing interest in role of viruses like Epstein–Bar virus, human papillomavirus, herpes simplex virus, hepatitis C virus etc., in oral carcinogenesis. Viruses act in inducing cancers through different methods. Perhaps knowing the exact role of viruses in precancerous lesions and cancers can affect the treatment plans and prognosis of the patients.

Keywords: Carcinogenesis, leukoplakia, malignancy, oral cancer, oral lichen planus, oral submucous fibrosis, virus

How to cite this article:
Patil SP, Kale LM, Sodhi SJ, Jadhav AS. Viruses: Role in oral squamous cell carcinoma and oral precancerous lesions. Univ Res J Dent 2016;6:102-7

How to cite this URL:
Patil SP, Kale LM, Sodhi SJ, Jadhav AS. Viruses: Role in oral squamous cell carcinoma and oral precancerous lesions. Univ Res J Dent [serial online] 2016 [cited 2017 Jun 25];6:102-7. Available from: http://www.urjd.org/text.asp?2016/6/2/102/181684

  Introduction Top

Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide and accounts for approximately 5% of malignant tumors in developed countries.[1] OSCC is a significant subset of the worldwide burden of head and neck squamous cell carcinomas (HNSCC). Prevalence and anatomic distribution of these lesions are associated with habits like tobacco, smoking, alcohol, etc., Therefore, the use of tobacco and alcohol are considered as a risk factors for OSCC, but it does not always show a positive correlation.[2] Individual that develops the precancer lesions or OSCC without prior habit history suggest that others factors can play a role in head and neck carcinogenesis.

It has been suggested that not only a habit but also chemical carcinogens, radiation energy, chronic irritation, and viruses play an important role in their etiology.[3],[4],[5],[6] Viruses such as herpes simplex virus (HSV), human papillomaviruses (HPV), hepatitis C, Epstein–Barr viruses (EBVs) have shown close association with the development of premalignant lesions/conditions and OSCC.[7],[8],[9]

  Oral Squamous Cell Carcinoma and Viruses Top

OSCC usually originates from the stratified squamous epithelium. The etiology or OSCC is complex and involves many factors. As already described tobacco, betel quid, and alcohol consumption are the major risk factors for developing OSCC.[10],[11] However, additional factors such as genetic predisposition, diet or oncogenic viruses, which causes impairment of physiological mechanisms of cellular proliferation control.[10] These viruses are classified under two categories:

Viruses strongly associated with oral squamous cell carcinoma

  • HPV
  • HSV.

Viruses less frequently associated with oral squamous cell carcinoma

  • EBV
  • Hepatitis C virus (HCV).

  Human Papillomavirus Top

The specific role of HPV in the development of premalignant lesions and OSCC continues to be debated topic.[12] Papillomaviruses are members of the papovaviridae family, which also included the vacuolating viruse (SV40) and polyoma viruses. The papillomaviruses are nonenveloped, circular, double-stranded DNA viruses, with a genome of about 8 kb.[7]


Papillomaviruses are classified according to their host range and the relatedness of their nucleic acids:

  1. Papillomavirus was first named according to its natural host, e.g. cottontail rabbit (Shope) papillomavirus, bovine papillomavirus, deer papillomavirus, HPV, etc.
  2. Based on clinical prognosis of their associated lesion they can be: Low-risk HPVs, which cause benign epithelial hyperplasia, and high-risk HPVs, e.g. HPV-16 and -18 infected lesions have high propensity for malignant transformation
  3. According to the International Agency for Research on Cancer:[13]
    • Group 1: HPV-16 and -18 as carcinogenic in humans
    • Group 2A: HPV 31 and 33 as probably carcinogenic in humans
    • Group 2B: Remaining HPVs as possibly carcinogenic.[7]

Carcinogenic potential of human papillomaviruses

DNA is the genetic constituent of HPV DNA. It contains three regions: A long control region, an early region, and a late region. When the host tissues get infected with HPV, E6 protein and E7 protein are formed following complete degradation of host genome. E6 protein forms a complex that causes degradation of p53 gene by inhibiting apoptosis while E7 protein causes an increase in DNA synthesis and proliferation which leads to disturbance in the retinoblastoma tumor suppressor gene. Basal keratinocytes are the target cells for HPV where new virions are produced and released subsequently when the superficial cells flake off.[14]

Correlation between human papillomaviruses and oral squamous cell carcinoma

Since the early 1980s, the presence of HPV (koilocytes) in OSCC cases has been proved. Almost 100 distinct types of HPV have been identified. However, not all types are associated with OSCC.[15] Studies have shown, high prevalence of HPV-16 and HPV-18 with OSCC from Indian betel quid chewers.[16],[17],[18],[19],[20] The constant detection of the HPV in OSCC patients who do not habitually use tobacco or consume alcohol has also pointed out the close association of HPV with OSCC.[21]

Evidences also suggest that the HPV-positive HNSCC patients are exposed to virus also through various sexual means.[22] Among various strains of HPV, HPV-16 is most commonly associated in these patients.

  Herpes Simplex Virus Top

HSV is a double-stranded DNA virus that is enveloped. The two most common forms are HSV 1 and HSV 2. HSV 1 mainly causes oral and ocular infections while HSV 2 causes genital infection. Both viruses have similar structures. Various functions of two viruses are encoded by identical regions of each virus.[23],[24] However, they have a difference in the ability to transform cells. The transforming region of HSV 1 is located in the left third of the genome. It is also known as minimum transforming region (mtr) 1, while in HSV 2, mtr 2, mtr 3 are close to the center of the genome.[25]

  Herpes Simplex Virus and Oral Squamous Cell Carcinoma Top

The explanation for the association between oral cancer and HSV could well be that of a confounding variable, except for the fact that HSV can transform some animal cells to a malignant phenotype in vitro.[26] Indeed, HSV has shown cocarcinogenic activity in combination with chemicals in vivo.[27] Unfortunately, the association is difficult to study, because cells that are transformed by HSV do not express specific virus antigens or retain any specific genes of the virus.[28] Instead it seems likely that the transformation is due to the virus acting as a mutagen, and a region of the viral genome has been isolated, which raises the mutation frequency in cultured cells.[29] This results in some but not all of the features of malignancy.[30] Neither the mutations nor the phenotypic changes are sufficiently specific to act as markers by which a herpes-induced malignancy could be diagnosed.[31] Recent years have seen little or no progress in the study of HSV and its malignant potential.

  Herpes Simplex Virus in Cell Transformation Top

The transforming mechanisms of HSV 1 and 2 remain obscure. The viruses have not been shown to encode an oncogene or related gene and furthermore the transforming regions of the genome are not retained in transformed cells. Galloway et al.[32] narrowed down the transforming region of HSV 2, mtr-2, to 793 base pairs of DNA. Even such a small amount of viral DNA was not retained by the transformed cells, leading to the so-called hit and run hypothesis of transformation by HSV proposed by Ambinder to be widely adopted.

Few other mechanisms that are proposed in cell transformations of HSV are:

  • Induction of cellular proteins
  • Host cell shut off process
  • Stimulation of other viruses by HSV
  • Chromosomes as targets.

  Epstein–bar Virus Top

EBV is named after Michael Anthony Epstein and Yvonne Barr, who discovered and documented the virus in 1964. It is also known as human herpes virus-4. It is one of the most common viruses in humans. It belongs to the genus Lymphocryptoviridae. It is a gamma 1 subtype of the subfamily Gammaherpesvirinae.[33] The virus consists of a linear double-stranded DNA core surrounded by a nucleocapsid and it is an enveloped virus. EBV is commonly associated with a number of malignancies such as Burkitt's lymphoma, Hodgkin's disease, stomach carcinomas, and nasopharyngeal carcinoma.[8]

Epstein–Bar virus and carcinogenesis

Depending upon the tumor type the mechanism of tumor causation by EBV varies. Establishment of a persistent infection the first stage in the mechanisms of EBV tumorigenesis.[34] The primary infection is believed to start within the oropharyngeal epithelial cells with viruses subsequently passing to subepithelial B-cells through direct contact. The invasion of the immune system by EBV stimulates CD8 T-cell response. The development of a virus-specific adaptive immune response reduces the number of EBV-infected B-cells subsequently leads to the elimination of EBV infection. This elimination of infection perhaps remains as a latent infection after incompletely persistent EBV infection in peripheral blood lymphocytes and/or as a lytic infection in the oral cavity. It results in the shedding of infectious viruses viaoral secretions. EBV infects resting B-cells and converts them to continuously proliferating lymphoblastoid cells. They express nine latency-associated viral proteins which includes six nuclear antigens (Epstein–Barr nuclear antigen [EBNA] - 1, 2, 3A, 3B, 3C and leader protein [LP]) and three membrane proteins (latent membrane protein (LMP) - 1, 2A and 2B).[35] Genomic instability is a hallmark of malignant transformation and is frequently associated with chromosomal aberrations such as reciprocal translocations, deletions, inversions, and duplications. They deregulate the expression of oncogenes or tumor suppressor genes.[36] It has been demonstrated that the EBV nuclear antigens (EBNA 1 and EBNA 3C, and the LMP 1) promotes genomic instability, DNA breaks and phosphorylation of histone H2AX.[37] EBNA 1 causes DNA damage by inducing reactive oxygen species, and DNA repair is inhibited in LMP 1 expressing cells through downregulation of the DNA damage-sensing kinase, ataxia telangiectasia mutated, reduction of phosphorylation of its downstream targets Chk2 and inactivation of the G2 checkpoint. EBNA 3C enhances the propagation of damaged DNA. Thus, it has been postulated that EBV independently targets multiple cellular functions involved in the maintenance of genome integrity which causes genomic instability which considered as a critical event in viral oncogenesis.

A positive correlation is also established between different grades of OSCC and EBV DNA positivity. A percentage positivity of EBV DNA increases from well differentiated OSCC to poorly differentiated OSCC.[37] This indicates role of EBV in neoplastic transformation in oral cancers.

  Hepatitis C Virus Top

HCV is RNA virus and was first identified and cloned in 1989. It is an enveloped single-stranded positive sense RNA virus having a diameter of about 50 nm and classified as a separate genus (hepacivirus) within the Flaviviridae family. It is an etiological agent for most cases of non-a, non-b hepatitis, liver cirrhosis, and hepatocellular carcinoma. A possible involvement of HCV in diseases outside the liver has been described in the literature. The oral cavity is frequently exposed to HCV viruses, thereby causing an increase in the risk of genetic instability in the cells.[38]

In HCV-positive patients, the squamous cells of oral cavity are continuously exposed to HCV from saliva as well as from serum. This might leads to the development of OSCC. Anti-HCV antibodies were also detected in patients with OSCC, but the exact mechanism is unclear.[39]

Oral premalignant lesions/conditions and viruses

The etiology of oral premalignant lesions is generally accepted to be multifactorial. Tobacco and alcohol are established as important cofactors in malignant development in the oral cavity, but in addition microorganisms have gained much interest since past decade. For many years, HPV has been accepted as an important cofactor in the development of cervical cancer, originating from a mucous membrane with similarities to the oral mucosa. Along with HPV other viruses like EBV, HCV have shown a role in the causation of oral premalignant lesions.

  Human Papillomavirus Top

Total 24 different types of HPV (1, 2, 3, 4, 6, 7, 10, 11, 13, 16, 18, 30, 31, 32, 33, 35, 45, 52, 55, 57, 59, 69, 72, and 73) have been associated with oral premalignant lesions.[39],[40] Premalignant lesions associated with HPV infection are oral leukoplakia (OL), oral erythroplakia (OE), oral submucous fibrosis (OSF), and smokeless tobacco keratosis.

OL has been defined as white plaques of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer. Szarka et al. detected HPV more frequently in patients with leukoplakia than in controls (P £ 0.001 in all comparisons). HPV prevalence increased gradually with increasing severity of the lesion of OLs.[41] In OL low-risk, HPV DNA is more commonly associated while high-risk HPV DNA are more frequently seen in OSCC.[42] Various studied have been carried out to determinate that the HPV genome is an independent clinicopathological factor as well as to detect different HPV-genotypes. However, they failed to determine the relationship between HPV-genotypes and clinicopathological factors. However, they conclude that the presence of HPV-16 was increased in OL and OSCC.[43] Hence, the correlation between OL malignant transformation and HPV infection was unclear. However, data suggests that HPV-infection could play an important role in oral carcinogenesis leading to malignant transformation of OL.

OE exact etiology of the lesion is unknown. However, it is assumed to be associated with OSCC.[44] but OE has increased malignant potential when compared with other precancerous entities. The role of HPV infection in OE is unclear. Some authors have described the role of HPV infection in OE together with p53 alterations.[45] Nielsen et al. also detected HPV infection (by situ hybridization and PCR) in potentially malignant oral lesions immunohistochemically. It has been suggested that HPV may be an etiologic co-factor involved in the development of oral cancer.[46] However, we cannot assume that HPV is the major etiologic factor involved in malignant transformation of OE.

Oral lichen planus (OLP) is a chronic mucocutaneous disorder which can also be present as a potentially premalignant lesion. A positive correlation has been also established between high-risk HPV and OLP. Especially, HPV-16 is found to be associated with OLP.[47]

Furthermore, Sand et al. evaluate the high-risk HPV-18 in approximately 27% of lichen planus cases but do not found statistical difference between HPV infection and oral lesions suggesting the pathologic correlation between HPV and OLP is unclear.[48]

OSF can be characterized by the submucosal deposition of dense connective tissue which subsequently causes reduced vascular supply to the tissues. Sub-epithelial vesicles can be seen in the early stages. While the older stage lesion shows epithelial atrophy with hyperkeratosis. Prevalence of HPV-16 in OSF and OSCC cases found a 91% prevalence of HPV-DNA in OSF. Hence, it can be postulated that epithelium lesions in OSF could be an important factor to integration of HPV mainly in basal cells genome.[49] Further, more studies are required to determine the exact role of HPV in the malignant transformation of OSF.

Smokeless tobacco keratosis is associated with the use of smokeless tobacco. Oral manifestations frequently seem to occur at the site of placement of smokeless tobacco. It includes mucosal lesions, that is, smokeless tobacco keratosis and gingival-periodontal disorders such as gingival recession, gingival inflammation, changes in gingival blood flow, and interproximal periodontal attachment loss.[50] The use of smokeless tobacco and the smokeless tobacco keratosis have been considered as a predisposing factors in development of oral cancers.[51] Clinically, the site of smokeless tobacco placement presents a leukoplakic lesion which is also known as “snuff dippers” lesions. It has been also detected that HPV-DNA relation between the three standard grades of smokeless tobacco keratosis lesions and HPV infection was observed.[52]

  Epstein Bar Virus Top

EBV is a herpes group virus that has been known to infect B lymphocytes. EBV has been found in lesions of Burkitt's lymphoma, nasopharyngeal carcinomas [8] and can readily transform B lymphocytes to immortal phenotype. Most common oral premalignant lesions associated with EBV are oral hairy leukoplakia and proliferative verrucous leukoplakia.

After initial infections, it is known that EBV persists in oral epithelial cells and often replicates in them. EBV is the proven etiological agent of nasopharyngeal carcinoma. EBV has also been detected in the precancerous lesion like hairy leukoplakia, that is, common in individuals infected with human immunodeficiency virus.[53],[54] Its role in the lesion is completely unknown. No malignant transformation has yet been reported in hairy leukoplakia which is mainly of diagnostic significance in patients with risk of AIDS.

Proliferative verrucous leukoplakia is a slow growing lesion which typically affects several areas. It has high-risk of malignant transformation to cancer especially OSCC and tendency to recur after treatment.[55],[56] Association between EBV and proliferative verrucose leukoplakia has proven, but an exact role in etiology is not yet clear.

  Hepatitis C Virus Top

The incidences of OLP, leukoedema, and leukoplakia in the subjects with HCV infection were significantly higher than those without HCV.[57]

The association of LP with viral agents has been of researcher's interest for a while. Accordingly, one of the most frequently reported oral extrahepatic manifestation of HCV infection is OLP.[58],[59] The association between HCV and LP was first described in 1990, a year after the discovery of the virus itself.[60] The investigations were all on antibody-based serological examination. Therefore, the probable association between HCV infection and OLP could not be proved initially.[61] Since OLP is also histologically a disease of squamous cells. The squamous cells of oral region are continuously exposed to HCV from saliva and from serum in HCV-positive patients, so this may be involved in the development of OLP in this patients.[62]

Nagao et al. suggested that anti-HCV antibodies were detected in sera of patients with OLP. The exact mechanism is unclear.[40] Gandolfo et al. found very high prevalence of anti-HCV antibodies in patients with OLP.

  Conclusion Top

Viruses are important risk factors for oral cancerous and precancerous lesions. While diagnosing these lesions one should always consider the possible role of viruses in their etiopathogenesis. Though the role of viruses in OSCC has been proved but further research is needed to provide adequate evidences to rule out their role in premalignant lesions/conditions. Recently, vaccines against HPV for prevention of cervical cancer have been invented. Similarly, further research is needed to develop a vaccine against these viruses in order to prevent the occurrence of oral premalignant and malignant lesion.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108.  Back to cited text no. 1
Soave DF, Nunes Celes MR, Oliveira-Costa JP, da Silveira GG, Zanetti BR, Oliveira LR, et al. The role of human papilloma virus in precancerous lesions and oral cancer. Ch. 9. 2013. p. 241-67.  Back to cited text no. 2
Chang F, Syrjänen S, Kellokoski J, Syrjänen K. Human papillomavirus (HPV) infections and their associations with oral disease. J Oral Pathol Med 1991;20:305-17.  Back to cited text no. 3
Hansson BG, Forslund O, Bjerre B, Lindholm K, Nordenfelt E. Human papilloma virus types in routine cytological screening and at colposcopic examinations. Eur J Obstet Gynecol Reprod Biol 1993;52:49-55.  Back to cited text no. 4
Scully C. Oral cancer: New insights into pathogenesis. Dent Update 1993;20:95-100.  Back to cited text no. 5
Kashima HK, Kutcher M, Kessis T, Levin LS, de Villiers EM, Shah K. Human papillomavirus in squamous cell carcinoma, leukoplakia, lichen planus, and clinically normal epithelium of the oral cavity. Ann Otol Rhinol Laryngol 1990;99:55-61.  Back to cited text no. 6
Steele C, Shillitoe EJ. Viruses and oral cancer. Crit Rev Oral Biol Med 1991;2:153-75.  Back to cited text no. 7
Metgud R, Astekar M, Verma M, Sharma A. Role of viruses in oral squamous cell carcinoma. Oncol Rev 2012;6:e21.  Back to cited text no. 8
Rakesh S, Janardhanan M, Vinodkumar RB, Vidya M. Association of human papilloma virus with oral squamous cell carcinoma – A brief review. J Oral Maxillofac Pathol 2010;1:63-6.  Back to cited text no. 9
Nemes JA, Deli L, Nemes Z, Márton IJ. Expression of p16(INK4A), p53, and Rb proteins are independent from the presence of human papillomavirus genes in oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;102:344-52.  Back to cited text no. 10
Rautava J, Luukkaa M, Heikinheimo K, Alin J, Grenman R, Happonen RP. Squamous cell carcinomas arising from different types of oral epithelia differ in their tumor and patient characteristics and survival. Oral Oncol 2007;43:911-9.  Back to cited text no. 11
Syrjanen S, Syrjanen K, editors. HPV infections of the oral mucosa. In: Papillomavirus Infections in Human Pathology. Ch. 17. New York: J. Wiley and Sons; 2000. p. 379-412.  Back to cited text no. 12
IARC. Monographs on the Evaluation of Carcinogenic Risks to Humans. Human Papillomaviruses. Vol. 90. Lyon: International Agency for Research on Cancer; 2007.  Back to cited text no. 13
Rakesh S, Mahija J, Vinodkumar RB, Vidya M. Association of human papilloma virus with oral squamous cell carcinoma - A brief review. Oral and Maxillofacial Pathology Journal 2010;1:1-9.  Back to cited text no. 14
Muñoz N, Bosch FX, de Sanjosé S, Herrero R, Castellsagué X, Shah KV, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003;348:518-27.  Back to cited text no. 15
Balaram P, Nalinakumari KR, Abraham E, Balan A, Hareendran NK, Bernard HU, et al. Human papillomaviruses in 91 oral cancers from Indian betel quid chewers – High prevalence and multiplicity of infections. Int J Cancer 1995;61:450-4.  Back to cited text no. 16
Chang F, Syrjänen S, Nuutinen J, Kärjä J, Syrjänen K. Detection of human papillomavirus (HPV) DNA in oral squamous cell carcinomas by in situ hybridization and polymerase chain reaction. Arch Dermatol Res 1990;282:493-7.  Back to cited text no. 17
Shroyer KR, Greer RO Jr. Detection of human papillomavirus DNA by in situ DNA hybridization and polymerase chain reaction in premalignant and malignant oral lesions. Oral Surg Oral Med Oral Pathol 1991;71:708-13.  Back to cited text no. 18
Mork J, Lie AK, Glattre E, Hallmans G, Jellum E, Koskela P, et al. Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med 2001;344:1125-31.  Back to cited text no. 19
Charfi L, Jouffroy T, de Cremoux P, Le Peltier N, Thioux M, Fréneaux P, et al. Two types of squamous cell carcinoma of the palatine tonsil characterized by distinct etiology, molecular features and outcome. Cancer Lett 2008;260:72-8.  Back to cited text no. 20
Andrews E, Seaman WT, Webster-Cyriaque J. Oropharyngeal carcinoma in non-smokers and non-drinkers: A role for HPV. Oral Oncol 2009;45:486-91.  Back to cited text no. 21
Heck JE, Berthiller J, Vaccarella S, Winn DM, Smith EM, Shan'gina O,et al. Sexual behaviours and the risk of head and neck cancers: A pooled analysis in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Int J Epidemiol 2010;39:166-81.  Back to cited text no. 22
Gillison ML, D'Souza G, Westra W, Sugar E, Xiao W, Begum S, et al. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst 2008;100:407-20.  Back to cited text no. 23
Filion M, Skup D, Suh M. Specific induction of cellular gene transcription in herpes simplex virus type 2-transformed cells. J Gen Virol 1988;69:2011-9.  Back to cited text no. 24
Corey L, Spear PG. Infections with herpes simplex viruses (1). N Engl J Med 1986;314:686-91.  Back to cited text no. 25
Rapp F, Duff R. Transformation of hamster embryo fibroblasts by herpes simplex viruses type 1 and type 2. Cancer Res 1973;33:1527-34.  Back to cited text no. 26
Hirsch JM, Johansson SL, Vahlne A. Effect of snuff and herpes simplex virus-1 on rat oral mucosa: Possible associations with the development of squamous cell carcinoma. J Oral Pathol 1984;13:52-62.  Back to cited text no. 27
Galloway DA, McDougall JK. The oncogenic potential of herpes simplex viruses: Evidence for a 'hit-and-run' mechanism. Nature 1983;302:21-4.  Back to cited text no. 28
Shillitoe EJ, Zhang S, Wang G, Hwang CB. Functions and proteins of herpes simplex virus type-1 that are involved in raising the mutation frequency of infected cells. Virus Res 1993;27:239-51.  Back to cited text no. 29
Mikola H, Waris M, Tenovuo J. Inhibition of herpes simplex virus type 1, respiratory syncytial virus and echovirus type 11 by peroxidase-generated hypothiocyanite. Antiviral Res 1995;26:161-71.  Back to cited text no. 30
Hwang CB, Shillitoe EJ. DNA sequence of mutations induced in cells by herpes simplex virus type-1. Virology 1990;178:180-8.  Back to cited text no. 31
Galloway DA, Nelson JA, McDougall JK. Small fragments of herpesvirus DNA with transforming activity contain insertion sequence-like structures. Proc Natl Acad Sci U S A 1984;81:4736-40.  Back to cited text no. 32
Ocheni S, Olusina DB, Oyenkunle AA, Jbegbulam OG, Kroger N, Bacher U, et al. EBV – Associated malignancies. J Open Infect Dis 2010;4:101-12.  Back to cited text no. 33
Kutok JL, Wang F. Spectrum of Epstein-Barr virus-associated diseases. Annu Rev Pathol 2006;1:375-404.  Back to cited text no. 34
Gruhne B, Sompallae R, Masucci MG. Three Epstein-Barr virus latency proteins independently promote genomic instability by inducing DNA damage, inhibiting DNA repair and inactivating cell cycle checkpoints. Oncogene 2009;28:3997-4008.  Back to cited text no. 35
Raptis S, Bapat B. Genetic instability in human tumors. EXS 2006;96:303-20.  Back to cited text no. 36
González-Moles M, Gutiérrez J, Ruiz I, Fernández JA, Rodriguez M, Aneiros J. Epstein-Barr virus and oral squamous cell carcinoma in patients without HIV infection: Viral detection by polymerase chain reaction. Microbios 1998;96:23-31.  Back to cited text no. 37
Johnson RJ, Gretch DR, Yamabe H, Hart J, Bacchi CE, Hartwell P, et al. Membranoproliferative glomerulonephritis associated with hepatitis C virus infection. N Engl J Med 1993;328:465-70.  Back to cited text no. 38
Nagao Y, Sata M, Itoh K, Tanikawa K, Kameyama T. Quantitative analysis of HCV RNA and genotype in patients with chronic hepatitis C accompanied by oral lichen planus. Eur J Clin Invest 1996;26:495-8.  Back to cited text no. 39
Kojima A, Maeda H, Sugita Y, Tanaka S, Kameyama Y. Human papillomavirus type 38 infection in oral squamous cell carcinomas. Oral Oncol 2002;38:591-6.  Back to cited text no. 40
Szarka K, Tar I, Fehér E, Gáll T, Kis A, Tóth ED, et al. Progressive increase of human papillomavirus carriage rates in potentially malignant and malignant oral disorders with increasing malignant potential. Oral Microbiol Immunol 2009;24:314-8.  Back to cited text no. 41
Miller CS, Johnstone BM. Human papillomavirus as a risk factor for oral squamous cell carcinoma: A meta-analysis, 1982-1997. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91:622-35.  Back to cited text no. 42
Llamas-Martínez S, Esparza-Gómez G, Campo-Trapero J, Cancela-Rodríguez P, Bascones-Martínez A, Moreno-López LA, et al. Genotypic determination by PCR-RFLP of human papillomavirus in normal oral mucosa, oral leukoplakia and oral squamous cell carcinoma samples in Madrid (Spain). Anticancer Res 2008;28:3733-41.  Back to cited text no. 43
Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and Maxilofacial Pathology. Philadelphia: W.B. Saunders Company; 2009.  Back to cited text no. 44
Reichart PA, Philipsen HP. Oral erythroplakia – A review. Oral Oncol 2005;41:551-61.  Back to cited text no. 45
Nielsen H, Norrild B, Vedtofte P, Praetorius F, Reibel J, Holmstrup P. Human papillomavirus in oral premalignant lesions. Eur J Cancer B Oral Oncol 1996;32B: 264-70.  Back to cited text no. 46
O Flatharta C, Flint SR, Toner M, Butler D, Mabruk MJ. Investigation into a possible association between oral lichen planus, the human herpesviruses, and the human papillomaviruses. Mol Diagn 2003;7:73-83.  Back to cited text no. 47
Sand L, Jalouli J, Larsson PA, Hirsch JM. Human papilloma viruses in oral lesions. Anticancer Res 2000;20:1183-8.  Back to cited text no. 48
Jalouli J, Ibrahim SO, Mehrotra R, Jalouli MM, Sapkota D, Larsson PA, et al. Prevalence of viral (HPV, EBV, HSV) infections in oral submucous fibrosis and oral cancer from India. Acta Otolaryngol 2010;130:1306-11.  Back to cited text no. 49
Chu YH, Tatakis DN, Wee AG. Smokeless tobacco use and periodontal health in a rural male population. J Periodontol 2010;81:848-54.  Back to cited text no. 50
Accortt NA, Waterbor JW, Beall C, Howard G. Cancer incidence among a cohort of smokeless tobacco users (United States). Cancer Causes Control 2005;16:1107-15.  Back to cited text no. 51
Greer RO Jr, Meyers A, Said SM, Shroyer KR. Is p16(INK4a) protein expression in oral ST lesions a reliable precancerous marker? Int J Oral Maxillofac Surg 2008;37:840-6.  Back to cited text no. 52
Greenspan D, Greenspan JS, Conant M, Petersen V, Silverman S Jr, de Souza Y. Oral “hairy” leucoplakia in male homosexuals: Evidence of association with both papillomavirus and a herpes-group virus. Lancet 1984;2:831-4.  Back to cited text no. 53
Greenspan JS, Greenspan D, Lennette ET, Abrams DI, Conant MA, Petersen V, et al. Replication of Epstein-Barr virus within the epithelial cells of oral “hairy” leukoplakia, an AIDS-associated lesion. N Engl J Med 1985;313:1564-71.  Back to cited text no. 54
Bagán JV, Murillo J, Poveda R, Gavaldá C, Jiménez Y, Scully C. Proliferative verrucous leukoplakia: Unusual locations of oral squamous cell carcinomas, and field cancerization as shown by the appearance of multiple OSCCs. Oral Oncol 2004;40:440-3.  Back to cited text no. 55
Feller L, Wood NH, Raubenheimer EJ. Proliferative verrucous leukoplakia and field cancerization: Report of a case. J Int Acad Periodontol 2006;8:67-70.  Back to cited text no. 56
Sata M, Fukuizumi K, Tanikawa K, Kameyama T. High incidence of oral precancerous lesions in a hyperendemic area of hepatitis C virus infection. Hepatol Res 1997;8:173-7.  Back to cited text no. 57
Khattab MA, Eslam M, Alavian SM. Hepatitis C virus as a multifaceted disease: A simple and updated approach for extrahepatic manifestations of hepatitis C virus infection. Hepat Mon 2010;10:258-69.  Back to cited text no. 58
Grossmann Sde M, Teixeira R, de Aguiar MC, do Carmo MA. Exacerbation of oral lichen planus lesions during treatment of chronic hepatitis C with pegylated interferon and ribavirin. Eur J Gastroenterol Hepatol 2008;20:702-6.  Back to cited text no. 59
Rebora A. HCV and lichen planus: HCV and lichen planus. Hepat Mon 2011;11:134-5.  Back to cited text no. 60
Roy K, Bagg J. Hepatitis C virus and oral disease: A critical review. Oral Dis 1999;5:270-7.  Back to cited text no. 61
Gandolfo S, Carbone M, Carrozzo M, Gallo V. Oral lichen planus and hepatitis C virus (HCV) infection: Is there a relationship? A report of 10 cases. J Oral Pathol Med 1994;23:119-22.  Back to cited text no. 62


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
   Oral Squamous Ce...
  Human Papillomavirus
  Herpes Simplex Virus
   Herpes Simplex V...
   Herpes Simplex V...
  Hepatitis C Virus
  Human Papillomavirus
  Epstein Bar Virus
  Hepatitis C Virus

 Article Access Statistics
    PDF Downloaded205    
    Comments [Add]    

Recommend this journal