The Role of the p16 and p53 Tumor Suppressor Proteins and Viral HPV16 E6 and E7 Oncoproteins in the Assessment of Survival in Patients with Head and Neck Cancers Associated with Human Papillomavirus Infections

Abstract

The role of HPV in the survival prognosis of patients with head and neck squamous cell carcinoma, especially patients with laryngeal squamous cell carcinoma (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC), is still somewhat ambiguous. The present study aimed to explore the significance of tumor suppressor proteins and HPV16 E6 and E7 oncoproteins in the assessment of survival in patients with oropharyngeal squamous cell carcinoma (OPSCC), LSCC, and HPSCC associated with high-risk (HR-) and low-risk (LR-) HPV infections. By utilizing molecular and immunohistochemical investigations of HNSCC samples and patient data, univariate and multivariate survival analyses were conducted. The presence of HPV DNA (LR- and HR-HPV) was associated with a better 5-year OS and DSS for OPSCC and LSCC. The IHC overexpression of HPV16 E6 protein and p16 protein was associated with better survival in the univariate (for OPSCC) and multivariate (OPSCC and HPSCC) survival analyses. The overexpression of p53 was associated with better survival in OPSCC. HPV infection plays a significant role in the tumorigenesis of HNSCC, and the immunohistochemical assessment of HPV16 E6 protein expression should be interpreted as a useful prognostic marker for OPSCC and HPSCC.

Enhancing Cervical Cancer Screening: Review of p16/Ki-67 Dual Staining as a Promising Triage Strategy

“…In response to this disruption, cells increase the production of p16 to counteract uncontrolled progression of the cell cycle [45,46]. Therefore, p16 overexpression is an indirect result of HPV oncogenic activity within the cell [47]. Because p16 overexpression is closely linked to the disruption of cell cycle control by high-risk HPV types, it serves as a surrogate marker of HPV-associated oncogenic activity [48].…”

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.…”

The Relationship between Furin and Chronic Inflammation in the Progression of Cervical Intraepithelial Neoplasia to Cancer: A Cross-Sectional Study

“…This integration results in uncontrolled replication of human papillomavirus oncoproteins and the release of pro-inflammatory molecules, and both together eventually cause chronic inflammation and the degradation of the tumor suppressor gene p53. Therefore, chronic inflammation is responsible for the progression of cervical dysplasia to cancer and HPV-mediated cancers [5,6].…”