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2009, Infectious Agents and Cancer
Human papillomavirus (HPV) is widespread and can cause latent infection in basal cells, with low HPV DNA copy-number insufficient for transmission of infection; can cause subclinical infection that is active but without clinical signs; or can cause clinical infection leading to benign, potentially malignant or malignant lesions. The HPV cycle is influenced by the stage of maturation of the infected keratinocytes, and the production of virions is restricted to the post-mitotic suprabasal epithelial cells where all the virus genes are expressed. Low-risk HPV genotypes are associated with the development of benign oral lesions, whereas highrisk HPV genotypes are implicated in the development of malignant epithelial neoplasms. The rôle of high-risk HPV as a causative agent in epithelial malignancy is different at different anatomical sites: it is almost invariably implicated in squamous cell carcinoma of the uterine cervix, fairly frequently implicated in squamous cell carcinoma of the oropharynx, and it is seldom implicated in squamous cell carcinoma of the mouth.
International Journal of Oncology, 2007
Human papillomaviruses (HPVs) are a group of host-specific DNA viruses, with a remarkable epithelial cell specificity: they have been reported principally in the anogenital tract, urethra, skin, larynx, tracheo-bronchial and oral mucosa. More than 100 different HPV types have been identified and classified as high (e.g. 16, 18, 31) or low (e.g. 11, 42, 36)-risk (HR and LR), based on their association with cervical carcinoma. The carcinogenic role of HR-HPV revolves mainly around two of its oncoproteins: HPV-E6 which promotes degradation of the p53 tumour suppressor gene product and HPV-E7 which modifies the pRb tumour suppressor gene product, inhibiting the activity of TGF-ß2. Since these viral oncoproteins are capable of transforming primary human keratinocytes from either genital or upper respiratory tract epithelia, they have been considered to play a role in disrupting cell-cycle regulatory pathways leading to a genetic progression to ano-genital cancer and, possibly, also to oral squamous cell carcinoma (OSCC). Recently, the oncogene HPV-E5 has also been found to transform cells by modulating growth factor receptors. On the basis of the high, although very variable, frequency of HR-HPV in OSCC, an oral malignant potential of HPV infection has been hypothesised but not definitively confirmed. Major aims of this review are to update the understanding of HPV activities with respect to oral oncology and to comment on the HPV DNA reported frequencies in OSCC and potentially malignant oral lesions. A computer database search was performed, through the use of MEDLINE (PubMED) and Cochrane Library, for the last three decades. Search key words used were: human papillomavirus, HPV and cancer, HPV and oral lesions, HPV and oral premalignant lesions, HPV and oral cancer, HPV and HNSCC, HPV and oral mucosa. The search was of all fields, all languages and all dates available. Contents 1. Human papillomavirus: identikit of a virus 2. HPV and oral oncology 3. Conclusions
Viruses
This study is focused on the epidemiological characteristics and biomolecular mechanisms that lead to the development of precancerous and cancerous conditions of oral lesions related to Human Papilloma Virus (HPV) infections. Current evidence from the literature demonstrates the role of HPV in potentially malignant oral disorders. Therefore, the underlying biomolecular processes can give arise, or contribute to, benign lesions as well as to oral carcinogenesis.
Journal of Oral Pathology & Medicine, 2008
BACKGROUND: Evidence is accumulating for the aetiological role of human papillomavirus (HPV) in the pathogenesis of potentially malignant oral mucosal lesions and squamous cell carcinomas. METHODS: Paraffin tissue sections from 49 patients with Ôwhite patches' of the oral mucosa were investigated histologically, by broad-spectrum PCR followed by genotyping and chromogenic in situ hybridisation (CISH). RESULTS: Histologically, 33 flat hyperplasias and 16 papillary hyperplasias were diagnosed. Twenty-two of 28 samples studied (78.6%) were positive for HPV DNA by PCR and six were negative. The following HPV types were detected in decreasing order of prevalence: HPV 35, HPV 6, HPV16, HPV 53, HPV 18, HPV 51 and HPV 55. Seventeen samples (60.7%) contained high-risk HPV DNA. Using CISH, ‡ 1 HPV signals were detected at least in a few epithelial cells in 95% of cases studied. All but one case were positive with the high-risk HPV probe and all HPV infections contained low viral load. Concordant positive results both by PCR and CISH were detected in 14 of 19 cases (73.7%) analysed. CONCLUSIONS: The high prevalence of HPV infection in hyperplastic Ôwhite patches' of the oral mucosa supports the putative role of HPV at an early stage of oral carcinogenesis. These results further indicate that the majority of white oral mucosal lesions -flat, exophytic, wart-like or papillary proliferations -could be considered as the clinical manifestations of oral HPV infection. This finding has clinical relevance regarding therapy and patient management and may help in elucidating the role of HPV infection in oral carcinogenesis.
International journal of oncology, 2007
Human papillomaviruses (HPVs) are a group of host-specific DNA viruses, with a remarkable epithelial cell specificity: they have been reported principally in the ano-genital tract, urethra, skin, larynx, tracheo-bronchial and oral mucosa. More than 100 different HPV types have been identified and classified as high (e.g. 16, 18, 31) or low (e.g. 11, 42, 36) -risk (HR and LR), based on their association with cervical carcinoma. The carcinogenic role of HR-HPV revolves mainly around two of its oncoproteins: HPV-E6 which promotes degradation of the p53 tumour suppressor gene product and HPV-E7 which modifies the pRb tumour suppressor gene product, inhibiting the activity of TGF-beta2. Since these viral oncoproteins are capable of transforming primary human keratinocytes from either genital or upper respiratory tract epithelia, they have been considered to play a role in disrupting cell-cycle regulatory pathways leading to a genetic progression to ano-genital cancer and, possibly, also ...
Human Papillomavirus and Related Diseases From Bench to Bedside A Diagnostic and Preventive Perspective, 2013
2011
Human papillomaviruses (HPV) has been an area of interest since last two decades because of its potential role in the pathogenesis of malignant tumors. Approximately 35 years ago a role of human papillomaviruses (HPV) in cervical cancer has been postulated. Today it is well established that this very heterogeneous virus family harbours important human carcinogens, causing not only the vast majority of cervical, but also a substantial proportion of other anogenital and head and neck cancers. This review will cover some of the pathogenetic aspects of papillomavirus research; it tries briefly to analyze the present state of linking HPV to human cancers and other oral lesions and will discuss some emerging developments.
International journal of immunopathology and pharmacology
Oncogenic HPVs are necessarily involved in cervical cancer but their role in oral carcinogenesis is debated. To detect HPV in oral cancer, 38 cases of formalin fixed-paraffin embedded OSCC were studied by both DNA genotyping (MY09/11 L1 consensus primers in combination with GP5-GP6 primer pair followed by sequencing) and immunohistochemistry (monoclonal Abs against capsid protein and HPV-E7 protein, K1H8 DAKO and clone 8C9 INVITROGEN, respectively). HPV-16 tonsil cancer was used as positive control. The overall prevalence of HPV infection in OSCCs was 10.5%. Amplification of DNA samples showed single HPV DNA infection in 3 cases (HPV16; HPV53; HPV70) and double infection in one case of cheek cancer (HPV31/HPV44). The overall HR-HPV prevalence was 7.5%. E-7 antigen was immunohistochemically detected in all HPV-positive cases. HPV+ OSCC cases showed an overall better outcome than HPV negative oral cancers, as evaluated by Kaplan-Meier curves. HPVs exert their oncogenic role after DNA ...
Acta Oto Laryngol, 2004
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 2014
Objective. This study aimed to examine atypical and malignant papillary oral lesions for low-and high-risk human papillomavirus (HPV) infection and to correlate HPV infection with clinical and pathologic features. Study Design. Sections of 28 atypical papillary lesions (APLs) and 14 malignant papillary lesions (MPLs) were examined for HPV by in situ hybridization and for p16 and MIB-1 by immunohistochemistry; 24 conventional papillomas were studied for comparison.
2004
BACKGROUND Oral human papillomavirus (HPV) prevalence varies according to geographical occurrence, the type of lesion, and the method of diagnosis. The polymerase chain reaction method (PCR) appears to be more sensitive and can be easily applicable to epidemiologic studies. OBJECTIVES To determine the frequency of HPV and its genotypes in oral lesions among patients attending a reference clinic of a university hospital. METHODS PCR was performed to identify HPV DNA from samples of oral epithelial lesions in 80 patients. For HPV DNA amplification, MY09/MY11 consensus primers were used and specific genotypes were identified through restriction fragment of length polymorphism (RFLP) pattern. RESULTS HPV DNA was present in 11.3% of patients, and the identified genotypes were 6b, MM4 (W13B), and MM9 (PAP238A). CONCLUSIONS HPV DNA frequency in patients with oral epithelial lesions was 11.3%. The genotypes MM4 and MM9 are uncommon in oral lesions, and they are characterized as high-risk HP...
BMC Oral Health, 2011
Background: The human papillomaviruses (HPV) are a large family of non-enveloped DNA viruses, mainly associated with cervical cancers. Recent epidemiologic evidence has suggested that HPV may be an independent risk factor for oropharyngeal cancers. Evidence now suggests HPV may modulate the malignancy process in some tobacco-and alcohol-induced oropharynx tumors, but might also be the primary oncogenic factor for inducing carcinogenesis among some non-smokers. More evidence, however, is needed regarding oral HPV prevalence among healthy adults to estimate risk. The goal of this study was to perform an HPV screening of normal healthy adults to assess oral HPV prevalence. Methods: Healthy adult patients at a US dental school were selected to participate in this pilot study. DNA was isolated from saliva samples and screened for high-risk HPV strains HPV16 and HPV18 and further processed using qPCR for quantification and to confirm analytical sensitivity and specificity. Results: Chi-square analysis revealed the patient sample was representative of the general clinic population with respect to gender, race and age (p < 0.05). Four patient samples were found to harbor HPV16 DNA, representing 2.6% of the total (n = 151). Three of the four HPV16-positive samples were from patients under 65 years of age and all four were female and Hispanic (non-White). No samples tested positive for HPV18. Conclusions: The successful recruitment and screening of healthy adult patients revealed HPV16, but not HPV18, was present in a small subset. These results provide new information about oral HPV status, which may help to contextualize results from other studies that demonstrate oral cancer rates have risen in the US among both females and minorities and in some geographic areas that are not solely explained by rates of tobacco and alcohol use. The results of this study may be of significant value to further our understanding of oral health and disease risk, as well as to help design future studies exploring the role of other factors that influence oral HPV exposure, as well as the short-and long-term consequences of oral HPV infection.
Viruses
Foot-and-mouth disease (FMD) is the most devastating disease of cloven-hoofed livestock, with a crippling economic burden in endemic areas and immense costs associated with outbreaks in free countries. Foot-and-mouth disease virus (FMDV), a picornavirus, will spread rapidly in naïve populations, reaching morbidity rates of up to 100% in cattle. Even after recovery, over 50% of cattle remain subclinically infected and infectious virus can be recovered from the nasopharynx. The pathogen and host factors that contribute to FMDV persistence are currently not understood. Using for the first time primary bovine soft palate multilayers in combination with proteogenomics, we analyzed the transcriptional responses during acute and persistent FMDV infection. During the acute phase viral RNA and protein was detectable in large quantities and in response hundreds of interferon-stimulated genes (ISG) were overexpressed, mediating antiviral activity and apoptosis. Although the number of pro-apopt...
Virulence, 2015
Increased awareness of human papillomavirus (HPV) as an etiological cause of head and neck squamous cell carcinoma has increased the interest in analysis of distinct oral sub-sites. It is currently under debate, whether HPV plays a role in the development of squamous cell carcinoma of the oral cavity (OSCC). The weakness in most published studies is the lack of performing different HPV detection tests combined with analysis for biological activity of the virus. In addition, different sub-sites of the oral cavity had been combined to a single entity, which retrospectively leads to a highly heterogeneous basis of data. In this review we mainly discuss the unclear role of HPV in OSCC development.
Journal of investigative and clinical dentistry, 2018
The increasing prevalence of human papilloma virus (HPV)-positive oral tumors can be considered an epidemic. Although the incidence of HPV cervical cancer is decreasing, the incidence of oral cavity and oropharyngeal cancers associated with HPV is increasing. The presence of certain HPV genotypes could be a predictor of future oral cancer lesions, although lesions associated with HPV could be less aggressive and exhibit a higher survival rate. In the present study, we review the most important biologic, clinic, epidemiologic, and prognostic factors associated with HPV infection and oral cancer.
Annals of Maxillofacial Surgery, 2021
Oral malignancy is a major global health problem and it constitutes the sixth-most common malignancy. [1] More than 90% of these malignancies representing squamous cell carcinoma (SCC), in the oral cavity are often preceded by preexisting oral lesions termed as potentially malignant disorders of the oral mucosa. [2] Oral SCC (OSCC) are characterized by a multiphasic and multifactorial etiopathogenesis. In India and other regions of Southeast Asia, it is the predominant malignancy, [3] accounting for up to 50% of all malignant tumours. Along with tobacco and alcohol, factors such as genetic predisposition, diet, and viral agents like human papillomavirus (HPV), [4] may also play a role in the initiation or development of oral carcinogenesis. Approximately 15% of all malignancies worldwide appear to be connected with viral infections and several human DNA viruses are now accepted as causative factors. [5] Majority of the head-and-neck malignancies originate from the epithelium which line the upper aerodigestive tract. [6] The epithelial areas of the upper aerodigestive tract display greatest susceptibility to HPV due to the exposure of the basal cells to HPV infection. [7] Among the strains, HPV-16
"Background Human papillomaviruses (HPV) are involved in the etiology of cervix cancer, but it is still unclear whether they play a role in related oral lesions. Objectives The presence of HPV in oral leukoplakia biopsies (n=50) and oral squamous carcinoma biopsies (n=50) was compared to normal oral mucosa swabs (n=50) for the purpose of indicating a possible etiological role for the virus. Study design DNA was extracted from tissue biopsies and from mucosa swabs of control samples. Nested PCR was performed with primers targeting conserved sequences within the capsid gene L1. PCR products were sequenced to identify the HPV genotype. Result The results reveal a profile of low-risk HPV genotypes in oral leukoplakia similar to that in healthy controls, while HPV was less frequently observed in oral squamous carcinoma. Conclusions HPV does not seem to represent an important causal factor for the development of oral leukoplakia or oral squamous carcinoma. "
Experimental cell research, 1996
granular cell layers . Although more than 70 dif-Human papillomavirus (HPV) has been implicated ferent types are now known , HPV shows a strong in the etiology of oral and cervical cancers. Normal type specificity for anatomical location and also for oral epithelial cells at passage two were infected characteristic type of lesions. Twenty-two types are with recombinant retrovirus containing the E6/E7 commonly found to infect the human anogenital tract open reading frames of HPV type 16. The G418-se- , and these virus types appear to have a role in lected cells that were immortalized and express HPV carcinogenesis of the anogenital region, in that more 16 E6/E7 have been in culture for over 4 years and than 90% of cervical cancers have been reported to 350 passages. In contrast, the normal oral epithelial contain HPV DNA [1]. HPV types 6 and 11 are found cells did not survive the culture environment beyond in benign condylomas, while types 16, 18, 31, and 32 7 to 9 passages. Fifteen clones were selected from are frequently associated with malignant progresthe pooled population. By Northern blot analysis all sion and cervical cancer [4 -7].
JNCI Journal of the …, 2003
Background: Human papillomavirus (HPV), the causal agent of cervical cancer, appears to be involved in the etiology of cancer of the oral cavity and oropharynx. To investigate these associations, we conducted a multicenter case-control study of cancer of the oral cavity and oropharynx in nine countries. Methods: We recruited 1670 case patients (1415 with cancer of the oral cavity and 255 with cancer of the oropharynx) and 1732 control subjects and obtained an interview, oral exfoliated cells, and blood from all participants and fresh biopsy specimens from case patients. HPV DNA was detected by polymerase chain reaction (PCR). Antibodies against HPV16 L1, E6, and E7 proteins in plasma were detected with enzyme-linked immunosorbent assays. Multivariable models were used for case-control and casecase comparisons. Results: HPV DNA was detected in biopsy specimens of 3.9% (95% confidence interval [CI] ؍ 2.5% to 5.3%) of 766 cancers of the oral cavity with valid PCR results and 18.3% (95% CI ؍ 12.0% to 24.7%) of 142 cancers of the oropharynx (oropharynx and tonsil combined) with valid PCR results. HPV DNA in cancer biopsy specimens was detected less frequently among tobacco smokers and paan chewers and more frequently among subjects who reported more than one sexual partner or who practiced oral sex. HPV16 DNA was found in 94.7% of HPV DNA-positive case patients. HPV DNA in exfoliated cells was not associated with cancer risk or with HPV DNA detection in biopsy specimens. Antibodies against HPV16 L1 were associated with risk for cancers of the oral cavity (odds ratio [OR] ؍ 1.5, 95% CI ؍ 1.1 to 2.1) and the oropharynx (OR ؍ 3.5, 95% CI ؍ 2.1 to 5.9). Antibodies against HPV16 E6 or E7 were also associated with risk for cancers of the oral cavity (OR ؍ 2.9, 95% CI ؍ 1.7 to 4.8) and the oropharynx (OR ؍ 9.2, 95% CI ؍ 4.8 to 17.7). Conclusions: HPV appears to play an etiologic role in many cancers of the oropharynx and possibly a small subgroup of cancers of the oral cavity. The most common HPV type in genital cancers (HPV16) was also the most common in these tumors. The mechanism of transmission of HPV to the oral cavity warrants further investigation. [J Natl Cancer Inst 2003;95:
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 2018
To find out the association between Human Papilloma Virus (HPV) genotypes 16/18 in Pakistani patients with oral squamous cell carcinoma (OSCC). DNA from oral rinse of 300 subjects was taken. The subjects included 100 cases with OSCC and 200 controls. Samples were analyzed by both conventional and real time PCR using "HPV consensus Gp5+/Gp6+ and HPV 16, 18 specific primers". Out of 300 persons, 74/300 (25%) were found to be infected with HPV: "46/100(46%) from cases and 74/200(14%) from controls". The distribution was: HPV16, 6/300 (8%): 4/100 (9%) from OSCC group and 2/200 (8%) from controls while HPV 18 was 9/300(12%): 5/100(11%) from cases and 4/200(16%) from controls. Out of 300 subjects, 26(35%) were infected by "both HPV 16/18 (23(50%) from cases and 3(12%) from controls". Persons who were infected with HPV 16&18 had higher chances to develop OSCC as compared to those who didn't have HPV 16/18 (AOR: 21.4, 95% CI: 5.73 - 80.8). The exposure to h...
Head & Face Medicine, 2010
High-risk human papillomavirus (HPV) E6 and E7 oncoproteins are essential factors for HPV-induced carcinogenesis, and for the maintenance of the consequent neoplastic growth. Cellular transformation is achieved by complex interaction of these oncogenes with several cellular factors of cell cycle regulation including p53, Rb, cyclin-CDK complexes, p21 and p27. Both persistent infection with high-risk HPV genotypes and immune dysregulation are associated with increased risk of HPV-induced squamous cell carcinoma.
Arşiv Kaynak Tarama Dergisi, 2017
Human papillomavirus (HPV) consists of a large group of double-stranded DNA viruses, belonging, to the family Papillomaviridae. HPV shows an affinity for squamous epithelium and may infect skin or mucosa. Mucosal infection by HPV may arise in various sites of its inoculation namely, the anogenital tract, urethra, skin, larynx, tracheobronchial and oral mucosa. It has been hypothesized that HPV may have a role in malignant potential of oral squamous cell carcinoma owing to its high frequency. This review aimed at highlighting the possible mechanism of infection of HPV, its possible role in oral and oropharyngeal carcinoma along with other features associated with the virus.
Journal of Microbiology Research, 2013
Hu man papillo mavirus (HPV) is considered a necessary factor for the development of cervical cancer; however, its relat ionship with oral cancer is controversial. The aim of this study was detect the presence of HPV in lesions of the oral cavity and its correlation with other risk factors. Presence of HPV was studied by polymerase chain reaction in samples fro m benign lesions, potentially malignant lesions (PML), neoplasias and healthy mucosae. The results from the different groups were co mpared; in addition to their histopathological variab les with tobacco smoking, alcohol consumption, so on. HPV was detected in 88.89% of benign lesions, 41.38% of PM L and 56.25% of neoplasias. The most prevalent genotypes were 16 and 6. Together, reached 55% of the total number of cases. A significant association was observed between HPV and male gender, tobacco smokers, alcohol drin kers and benign lesions. Tobacco smoking and alcohol intake were associated to neoplasias. Our results showed that factors like tobacco smoking and alcohol drinking, have more influence than HPV in the development o f oral neoplasias; however, 56.2% of the neoplasias tested positive for HPV; the percentage of HR-HPV detection increased with the severity of the lesions, suggesting its possible involvement in malignant processes
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