Prevalence of human papillomavirus16 DNA and p16^INK4a protein in oral squamous cell carcinoma: A systematic review and meta-analysis

Abstract

Background and Aim:Indian patients with oral squamous cell carcinoma (OSCC) are etiologically associated with the use of tobacco and alcohol; yet, a proportion of tumors that may harbor human papillomavirus (HPV) infections cannot be neglected. The following meta-analysis was conducted to address the association of p16INK4a and HPV DNA with OSCC. In addition, the study also provides the updated prevalence of HPV-induced OSCC.Materials and Methods:Literature survey was performed using databases such as PubMed with the help of the following keywords – “HPV infection,” “oral squamous cell carcinoma,” “p16INK4a,” “HPV DNA,” “E6,” “E7,” “L1,” “L2” and “LCR.” Proportion method was performed to derive the forest plot using MedCalc statistical software version 16.4.3.Results:Among 145 research articles, 33 articles were selected for further analysis, in which 13 articles were related to HPV DNA detection in tissues, 11 articles detected the overexpression of p16INK4a and nine articles reported the detection of both HPV DNA and p16INK4a expression. Meta-analysis revealed significant heterogeneity (P < 0.0001) among the articles. Overall, the study consisted of 3339 patients with OSCC, among which 559 patients were diagnosed with the presence of HPV16 DNA with a random proportion of 20.1% at 95% confidence interval (CI) (13.9–27.1, P < 0.0001). Overexpression of p16INK4a protein was observed in 709 patients with a random proportion of 25.4% at 95% CI (14.3–38.3, P < 0.0001).Conclusion:HPV DNA and expression of p16INK4a was suggested as gold standard for the detection of HPV infection in many cases of cancers. Frequency of HPV infection is significantly higher in patients with OSCC as identified through the detection of HPV DNA and p16INK4a expression. Even though the association of HPV infection has been established in head and neck cancer, this review could further the establishment of molecular level interaction of HPV in patients with oral cancer.

Association of Salivary Human Papillomavirus Infection and Oral and Oropharyngeal Cancer: A Meta-Analysis

“…As we expected, salivary HPV16 showed a higher prevalence in oropharyngeal cancer (39.6%) than oral cancer (18.6%), in accordance with previous studies [37,39,40]. In particular, the salivary HPV16 prevalence in our study was slightly higher in oral cancer than reported in a meta-analysis by Nydiae et al [37] (18.6% vs 14.9%), however, other authors have reported higher rates of HPV16 prevalence in oral carcinoma, ranging from 20% to 50% [41][42][43]. Salivary HPV18 was another oncogenic HPV type commonly evaluated by the included studies.…”

Combination of IFITM1 knockdown and radiotherapy inhibits the growth of oral cancer

“…However, a higher incidence of oral cancer is observed in South‐East Asia, likely attributed to excessive use of tobacco. The ratio of males to females diagnosed with oral cancer in India has been reported to be 2:1, indicating a higher occurrence among males . It is estimated that there are approximately 48 330 new cases and 9570 deaths due to oral cancer in the US annually.…”

Human papillomavirus detection in oropharyngeal squamous cell carcinoma using p16 immunohistochemistry

“…In which, 32 studies have shown deep association of HPV with OPSCC and OSCC, of which 14 studies seemed to be significantly positive; these studies have shown that the prevalence of HPV in India varies across depending on the lifestyle differences and geographic regions; there is an increased HPV association in OPSCC and OSCC in South India than the Western and Eastern parts of India. [3161718] Apart from geographic location, the incidence of HPV-induced OPSCC also varies with the genotype of virus. polymerase chain reaction (PCR) was a commonly used test, and it has been proved to be more sensitive in detection of HPV in OPSCC, than IHC and in situ hybridization (ISH).…”

“…HPV is an epitheliotropic, nonenveloped virus of Papillomaviridae family with double-stranded circular DNA genome. [321] Autonomous, specific, and strong carcinogenic effect of HPV is difficult to justify. Unprotected and erratic sexual behavior has a high risk of incidence of HPV, especially in younger age group.…”

“…[12] Approximately, 45% of cancer cases in India are diagnosed as oral cancer, among which 20%–50% of the cases are observed to be associated with human papillomavirus (HPV) infection. [3]…”