p16INK4a and pRb expression in laryngeal squamous cell carcinoma with and without infection by EBV or different genotypes of HPV: a retrospective study

Abstract

Background Laryngeal squamous cell carcinoma (LSCC) represents one of the principal tumors of the head and neck. Human papillomavirus (HPV) and Epstein–Barr virus (EBV) are considered risk factors for the development and the clinical prognosis of LSCC. High levels of p16INK4a are suggested as a surrogate marker of HPV or EBV infection in some head and neck tumors but in LSCC is still controversial. Furthermore, pRb expression may be considered an additional biomarker but it has not been clearly defined. This work aimed to compare the expression of pRb and p16INK4a as possible biomarkers in tumor tissues with and without infection by EBV or different genotypes of HPV from patients with LSCC. Methods Tumor samples from 103 patients with LSCC were previously investigated for the presence and genotypes of HPV using the INNO-LiPA line probe assay and for the infection of EBV by qPCR. p16 INK4a and pRb expression was assessed by immunohistochemistry. Results Of the 103 tumor samples, expression of p16INK4a was positive in 55 (53.4%) and of this, 32 (56.1%) were positive for HPV whereas 11 (39.3%) were EBV positive but both without a significantly difference (p > 0.05). pRb expression was positive in 78 (75.7%) and a higher frequency of this expression was observed in HPV negative samples (87.0%) (p = 0.021) and in high-risk HPV negative samples (85.2%) (p = 0.010). No difference was observed when comparing pRb expression and EBV infection status (p > 0.05). Conclusion Our results support the suggestion that p16INK4a is not a reliable surrogate marker for identifying HPV or EBV infection in LSCC. On the other hand, most of our samples had pRb expression, which was more frequent in tumors without HPV, suggesting that pRb could indicate HPV negativity. However, more studies with a larger number of cases are required, including controls without LSCC and evaluating other molecular markers to determine the real role of p16INK4a and pRb in LSCC.

Updates on Larynx Cancer: Risk Factors and Oncogenesis

“…The role of EBV in LSCC is controversial, as difficulties have been reported in detecting its presence in this type of cancer or it has shown a low prevalence [ 33 ]. However, both EBV and HPV are viruses capable of producing oncoproteins that can promote carcinogenesis and tumor progression [ 34 ].…”

Current and Emerging Diagnostic, Prognostic, and Predictive Biomarkers in Head and Neck Cancer

“…HPV is detected in a subset of HNCs outside of the oropharynx (larynx, oral cavity, hypopharynx, nasopharynx); however, the prevalence is much lower than in the oropharynx and the clinical significance is unclear [42]. While the prevalence of HPV positivity has been increasing in laryngeal and oral cavity cancer, there does not seem to be an association between HPV status and survival [43,44]. At this time, testing for HPV in non-oropharynx HNCs is not currently recommended [45].…”

P53 and pRB induction improves response to radiation therapy in HPV-positive laryngeal squamous cell carcinoma

“…Many studies have confirmed that HPV mainly combines with the tumor suppressors p53 and pRB through the E6 and E7 proteins to cause uncontrolled cell proliferation, resulting in damage or even loss of cellular DNA self-repair function, leading to cancer. 7 , 8 , 9 , 10 The characteristic of HPV E6 protein is that it has two structural domains, which contain zinc finger structures, and these zinc finger structures bind to DNA and RNA and mediate protein-protein interactions to realize the cell transformation of E6 protein. 11 The E6 protein mainly causes mutations in the tumor suppressor gene p53 and binds to the p53 protein, leading to its inactivation and degradation of the p53 protein, thereby causing malignant expansion of cells.…”