Article

Frequency of HPV-16 in Saliva and Blood in Head and Neck Squamous Cell Carcinoma in Pakistani Population

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Abstract

OBJECTIVE: Pakistan is geographically located in the region where prevalence of head and neck squamous cell carcinoma (HNSCC) is high. Human papilloma virus (HPV) subtype-16 plays significant role in heterogeneity of HNSCC. The objective of this study was to evaluate the frequency of HPV-16 in both blood and saliva in HNSCC in our population and its association with clinicopathological features. METHODOLOGY: A total of 200 samples comprising 100 blood and 100 saliva samples were collected. Hundred samples (saliva; n=50, blood; n=50) were collected from histopathologically confirmed head and neck squamous cell carcinoma patients and 100 samples (saliva; n=50 saliva, blood; n=50) were collected from healthy individuals without a history of cancer as controls. HPV-16 was detected using conventional polymerase chain reaction and gel-electrophoresis. The frequency and distribution of clinicopathological variables were calculated in percentages. Chi-square test was used to analyze the association of HPV-16 positivity with clinicopathological variables. RESULTS: Of 100 samples from HNSCC patients, 11 (11%) samples were positive for HPV-16. Of 11 HPV-16 positive samples, 8 (16%) were detected in saliva (n=50) and 3 (6%) were detected in plasma (n=50). Of 100 samples from control group, both blood and saliva samples were negative for HPV-16. No statistically significant association was found between HPV-16 in saliva and blood and clinicopathological characteristics (P > 0.05). CONCLUSION: Within the limit of current study, HPV-16 has a low-frequency in saliva and blood in HNSCC in our population. Further studies on HNSCC with large sample and HPV-subtypes are suggested. KEYWORD: Blood; human papilloma virus; saliva; squamous cell carcinoma. HOW TO CITE: Saher S, Syed SA, Iqbal A, Syed FA, Amin F, Sultan A, Anees M. Frequency of HPV-16 in saliva and blood in head and neck squamous cell carcinoma in Pakistani population. J Pak Dent Assoc 2020;29(4):228-234.

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Since there is evidence that human papillomavirus (HPV) may play some role in oral carcinogenesis, we investigated the presence of HPV in a group of Pakistani subjects with normal oral cavity using real-time PCR analysis. Two-hundred patients attending the Dental Department, Sandaman Provincial Hospital, Balochistan, Pakistan, were recruited. After interview, oral epithelial cells were collected by scraping and subjected to DNA extraction. The HPV-positive DNA samples were further analyzed using primer sets specific for HPV-16 and -18. It was found that out of 200 DNA samples, 192 were PCR-positive for the β-globin gene and these were subsequently examined for the presence of HPV DNA. Among these, 47 (24.5%) were HPV-positive with the virus copy number ranged between 0.43-32 copies per 1 μg of total DNA (9-99 copies per PCR reaction). There were 4 and 11 samples containing HPV-16 and -18, respectively. Additionally, one sample harbored both types of HPV. Among the investigated clinical parameters, smoking habit was associated with the presence of HPV (p=0.001) while others indicated no significant association. The prevalence of HPV in normal oral cavity in our Pakistani subjects appears to be comparable to other studies. However, the association between the presence of HPV and smoking warrants further investigations whether both of these factors can cooperate in inducing oral cancer in this group of patients.
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Human papillomavirus type 16 (HPV16) is a common infection in the anogenital tract. HPV16 DNA detected in oral specimens has recently been identified as a risk factor for some oropharyngeal cancers. The reported prevalence of oral HPV infection from individual studies is highly variable. We systematically reviewed and abstracted data from published studies (n = 18) that detected oral HPV DNA in 4581 cancer-free subjects to determine the pooled prevalence (and 95% confidence intervals [CI]) of HPV16, carcinogenic HPV, and any HPV. 1.3% (95% CI: 1.0-1.7%) of 3977 healthy subjects had oral HPV16, 3.5% (95% CI: 3.0-4.1) of 4441 subjects had carcinogenic HPV, and 4.5% (95% CI: 3.9-5.1) of 4070 subjects were positive for any HPV. Oral HPV16 accounted for 28% of all HPV detected in the oral region. Men (47 of 1017) and women (117 of 3690) had nearly exactly the same prevalence of any oral HPV detected (4.6% vs. 4.4%, respectively). HPV-16, a common anogenital infection, was rarely detected in oral specimens. However, a small but noteworthy proportion of healthy individuals have oral HPV infections with types known to cause cancer in the oral region.
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Over the past 20 years, high-risk human papilloma-virus (HPV) infection has been established as a risk factor for developing head and neck squamous cell carcinoma, independent of tobacco and alcohol use. In particular, HPV is strongly associated with the development of oropharyngeal cancer and a small minority of oral cavity cancers. In this review, we summarize what is currently known about the biology of HPV, the mechanisms by which it effects malignant transformation, and the potential impact of HPV status on the clinical management of persons with head and neck cancer.