Human Papillomavirus In Oral Cancer Research Articles

Prevalence of human papillomavirus in oral cancer in Asia: A systematic review and meta-analysis.

To determine the prevalence of human papillomavirus (HPV) in oral squamous cell carcinoma (OSCC) across Asian countries, focusing on South and Southeast Asia. A systematic search of four databases-MEDLINE/PubMed, EMBASE, Scopus, and ProQuest-was conducted to identify observational studies published between January 2013 and December 2023. The pooled prevalence of HPV was estimated using random-effects models, and subgroup analysis was performed to investigate the source of heterogeneity. A total of 77 studies were included, comprising 7289 OSCC cases from 11 countries. The pooled HPV prevalence in OSCC was 23.1% (95% CI 17.9-28.7, I2 = 96.7%). South Asia had the highest prevalence (27.1%), followed by East Asia (19.4%), and Southeast Asia (16.7%). Two subtypes were commonly reported: HPV-16 (9.1%) and HPV-18 (5.1%). Anatomical subsites, buccal mucosa (34.0%), and floor of the mouth (33.2%) had similar ranges of HPV prevalence. All studies exhibited a high degree of heterogeneity, with the OSCC location and risk of bias identified as potential sources of heterogeneity. Due to the high HPV prevalence in OSCC in Asia, HPV detection in routine pathology practice is recommended. Future studies should be conducted in multicentre settings using similar HPV detection methods and reporting detailed demographic and clinical information on oral sub-sites.

Assessing the nature of the association of human papillomavirus in oral cancer with and without known risk factors

BackgroundPublished studies assessing the association of human papillomavirus (HPV) and oral cancer, often include cases with additional confounders such as alcohol, tobacco, thus, precluding the assessment of HPV as a independent risk factor. Further apart from eliciting the mere presence of HPV, it is vital that the nature of the association is delineated for eliciting a causal inference. Thus, the present study assessed the presence and nature of the association of HPV in oral cancer cases with and without known risk factors.MethodsThe study compares the prevalence of HPV in oral cancer cases with known risk factors (group 1, n=15) to oral cancer (group 2, n=15) and oral epithelial dysplasia (group 3, n=15) cases with no known risk factors using PCR. Cases which are positive for HPV were subjected to p16 and p53 immunostaining to determine potential causal inference.ResultsHPV 16 was detected in only 1 case of group I, 3 cases of group II, and was absent in group III. HPV 18 was negative in all the 3 groups. All the HPV positive cases were negative for p16 and positive for p53 immunostaining.ConclusionsOnly a minor proportion of oral cancer cases without risk factors were positive for HPV 16. Even among these HPV 16 positive cases, the immunostaining profile (p53 positive and p16 negative) excludes the involvement of E6 and E7 mediated carcinogenesis. Thus even the weak HPV association noted in the present study cases may not be of causal nature.

Predictivity of human papillomavirus positivity in advanced oral cancer.

Human papillomavirus (HPV) is a known prognostic factor world over in patients of carcinoma oropharynx. The role of HPV in oral cancers has not been investigated adequately. We tried to identify standard clinicopathological features in oral cancer, which would predict HPV-positivity. This was a retrospective analysis of 124 cases of T4 oral cancer patients at our center. HPV-positive was defined in accordance with positive p16 immunohistochemistry done on pretreatment local tumor site biopsy. Age, sex, habits (smoking history and oral tobacco), Eastern Cooperative Oncology Group performance status (ECOG PS), T stage, N stage, grade, and site were selected, for testing of prediction for HPV-positivity. The analysis was performed by R studio version 3.1.1. Two-sample test for equality of proportions with continuity correction was used to identify factors predicting for HPV-positivity. P = 0.05 was considered as significant. Of 124 patients, 16 patients (12.9%) were HPV-positive. The median age of the whole cohort was 43 years (interquartile range 37-52 years) with 15 females (12.1%). All had squamous cell carcinoma (100%). The grade of the tumor was well differentiated in 9 patients (7.2%), moderately differentiated in 98 patients (79.1%), and poorly differentiated in 17 patients (13.7%). The ECOG PS 0 in 19 patients (15.3%), 1 in 104 patients (83.9%), and 2 in 1 patient (0.8%). The subsite of the tumor was buccal mucosa in 74 patients (59.7%), anterior two-third of tongue in 33 patients (26.6%), and others in 17 patients (13.7%). None of the tested factors except the use of oral tobacco were statistically significantly associated with HPV-positivity. History of tobacco usage had a statistical trend toward ability to predict HPV-positivity. The proportion of patients with HPV-positive oral cancer in patients without history usage of oral tobacco was 31.3% while it was 10.2% in patients with previous history of tobacco use (P = 0.03). Standard clinicopathological variables could not predict for HPV-positivity. Negative history of tobacco (smokeless) usage showed statistical trends toward ability to predict HPV-positivity in oral cancer patients.

Analysis of Human Papilloma Virus 16/18 DNA and its Correlation with p16 Expression in Oral Cavity Squamous Cell Carcinoma in North-Eastern India: A Chromogenic in-situ Hybridization Based Study.

The incidence of head and neck squamous cell carcinoma (HNSCC) is quite high in North Eastern India. Apart from the traditional risk factors like tobacco and alcohol consumption, human papilloma virus (HPV) is now considered an established causative agent. These HPV related tumour have a clinico-pathological profile that is quite divergent from conventional non-HPV related tumours. Association of HPV in oral cancers has not been explored in north-east India. Thirty-one patients with oral cavity squamous cell carcinoma (OSCC) on treatment from October 2010 to January 2013 were included in the study. Patients who received neo-adjuvant chemotherapy were excluded. HPV 16/18 DNA was evaluated using Chromogenic in-situ Hybridization (CISH). Presence of nuclear signals was taken as positive HPV expression. p16 was evaluated using immunohistochemistry and was considered positive if ≥ 80% of the tumour cells showed strong and diffuse nuclear/cytoplasmic immunostaining. The results were analysed using Fisher exact test and confidence interval was calculated where required. The study group age ranged from 30 to 80 years (median age- 54.2 years). The most common site was gum, with well differentiated squamous cell carcinoma being the most common histology. HPV 16/18 DNA was positive in 29% (95% CI: 13.03% - 44.97%) cases and had a clear tendency towards statistical significance with non-smoker cases (p=0.05), lymph node metastasis (p=0.05) and a significant correlation with p16 overexpression (p=0.04). There was no significant correlation with other clinico-pathological parameters. HPV 16/18 is associated with OSCC, commonly seen among non-smokers and may be related to nodal metastasis. So, HPV may be used as a prognostic factor in OSCC and p16 may be considered as a surrogate marker for HPV.

Human Papilloma Virus and oral cancer: Narrative review of the literature

The Human Papilloma Virus (HPV) infection is now more com- mon sexually transmitted diseases, with an incidence of 5.5 million worldwi- de, with 85% of the carrier of this virus adult population. Their oncogenic potential and increased oral lesions associated with oral HPV infection have led us to make a narrative review of the literature on the role of HPV in oral cancer, especially types 16 and 18. Here we refer to the possible routes of infection, oncogenic mechanisms, both benign and potentially malignant oral lesions associated with the infection, different methods used for detec- tion, prediction and prevention of infection. We stress the importance of the role of the dentist to identify individuals considered high risk and ease of performing detection in the oral cavity, through a quick and easy method as exfoliative cytology.

PP054: The role of human papillomavirus in oral cancer

Introduction In 1983 Stina Syrjanen found morphological similarities between oropharyngeal cancer and genital epithelia affected by human papillomavirus. In several epidemiologic studies, tobacco smoking and alcohol consumption have been well documented as major risk factors for oral cancer, with attributable fractions of approximately 90%. However, 15–20% of head and neck cancers have no known tobacco or alcohol exposure. Materials and methods We performed a systematic review in Medline/PubMed database about the relationship between oral cancer and human papillomavirus. We used: Key word (MeSH Database): mouth neoplasm, oral cancer, HPV, oropharynx cancer, human papillomavirus. Searching criteria: Type of study (clinical trial, metaanalysis, randomized clinical trial), idiom (english), object of study (human being), time (last five years). Results 16 articles were included in our study. (3 Meta-analysis, 3 prospective controlled case-control, 5 clinical trials, 3 cohortes, 2 experimental studies. We observed clinical and methodological bias. Most of oropharyngeal cancer are associated with human papillomavirus infection but there is not scientifical evidence about other oral cancer. Conclusions the relationship between oral cancer, except oropharyngeal cancer, and human papillomavirus infection is not demonstrated in the scientific literature.

Human Papillomavirus in oral Cancer: An immunohistochemical study

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Differential expression and activation of NF‐κB family proteins during oral carcinogenesis: Role of high risk human papillomavirus infection

Oral cancer is one of the most common cancers in India and south-east Asian region consisting of more than 50% of all malignant tumors. Along with many known risk factors, infection of Human Papillomavirus (HPV) has been associated with the development of oral cancer and is suggested to modulate host cell transcription. Reciprocally, cellular transcription factors, such as NF-kappaB and AP-1 are known to modulate the expression of viral and other genes involved in the development of cancer. In the absence of data on NF-kappaB in relation to HPV in oral cancer, we studied the DNA binding activity and expression pattern of NF-kappaB family of proteins in different stages of oral cancer and correlated with HPV infection that has been associated with better prognosis of the disease. A total of 110 fresh oral tissue biopsies were collected comprising 10 normal controls, 34 precancer and 66 oral cancer lesions prior to chemotherapy/radiotherapy. Diagnosis of HPV was done by both consensus and type-specific PCR. Electrophoretic mobility shift assays, western blots and immunohistochemical analysis were performed to assess the binding activity and expression pattern of NF-kappaB family of proteins (p50, p65, p52, c-Rel, RelB and Bcl-3) in oral tissue biopsies. Twenty seven percent (18/66) of the oral cancer biopsies showed the presence of HPV infection exclusively of high risk HPV type 16, which was primarily associated with the well differentiated squamous cell carcinomas (WDSCC). We observed a high constitutive activation of NF-kappaB with concomitant upregulated expression of all the NF-kappaB members in oral cancer tissues. Expression of NF-kappaB components gradually increased as the severity of lesion increased from precancer to invasive cancer. NF-kappaB p50 was found to be the major DNA binding component, which is indicative of homodimerization of p50 subunits. Interestingly, in HPV16 infected oral cancers although p50 showed high binding activity, p65 also showed a partial involvement as evidenced in supershift assay. Both by western blotting and immunohistochemistry, a differential overexpression and nuclear localization of p50, p65 and partially of Bcl-3 were observed in HPV16 positive oral cancer patients that also showed an over-expression of p21. We therefore, demonstrate a constitutive activation and differential expression of NF-kappaB proteins, which change as a function of severity of oral lesions during development of oral cancer. The NF-kappaB DNA binding is primarily due to homodimerization of p50 but infection of high risk HPV promotes participation of p65 in NF-kappaB complex formation, leading to heterodimerization of p50/p65. We propose that the involvement of p65 in HPV infected oral cancer may be linked to improved differentiation and better prognosis of the disease when treated.

Oral Human Papillomavirus Infection in Adults Is Associated with Sexual Behavior and HIV Serostatus

The prevalence and risk factors for oral human papillomavirus (HPV) infection are unknown, despite evidence for an etiological role for HPV in oral cancers. Oral samples from human immunodeficiency virus (HIV)-seronegative (n=396) and HIV-seropositive (n=190) adults were tested for HPV DNA. High-risk HPV infections were present in 2.1% of tonsil and 6.3% of oral-rinse specimens. The prevalence of oral high-risk HPV infection was greater in HIV-seropositive individuals (13.7% vs. 4.5%; P<.001). In multiple logistic regression, odds of oral HPV infection increased with age, male sex, and herpes simplex virus (HSV)-2 seropositivity in HIV-seronegative individuals and with CD4 cell count <200 cells/mL, HSV-2 seropositivity, oral mucosal abnormalities, and >1 oral sex partner during the previous year (odds ratio, 12.8; 95% confidence interval, 3.1-52.7) among HIV-seropositive individuals. HPV type 16, which is present in most HPV-associated tonsillar cancers, was the most prevalent high-risk oral HPV infection.

Human Papillomavirus in Oral Cancer from Sri Lanka: Prevalence and relationship with clinico-pathological parameters.

The presence of human papillomavirus (HPV) in two groups of oral squamous cell carcinoma (OSCC) from Sri Lanka were analyzed by PCR and direct cycle sequencing using consensus GP5+/6+ primers. The two groups of OSCC specimens analyzed were 68 formalin-fixed paraffinembedded surgical specimens and 34 formalin-fixed unembedded biopsies. Twenty-five patients from the latter group were habitual betel quid chewers. The HPV prevalence of the overall sample was 38/102 (37.2%). However, HPV was detected in significantly higher rate from formalin-fixed unembedded biopsies (61.7%) compared to paraffin embedded surgical specimens (25%) (p<0.0003). Upon sequencing, high-risk HPV types, 16,18, 45 and 66 were detected in 65% of the HPV infected tumors. Moreover, HPV was detected at significantly higher rates from small primary tumors (T1&T2) (75%) compared to large primary tumors (T3&T4) (30%) (p<0.025). However, no correlation existed between other clinico-pathological variables such as age, gender, sites, habits or histological differentiation and HPV detection when analyzed statistically using Pearson's chi-square test (at 5% level of significance). In conclusion, high prevalence of HPV in formalin fixed-unembedded OSCC biopsies from Sri Lanka indicate that, in addition to betel quid, viral infection may play a role in oral carcinogenesis and support the multi-factor model for oral cancer causation.