Prevalence and Prognostic Value of HPV among Tunisian Patients with Laryngeal Cancer and Relationship between DNA HPV and p16, IGF-1R, Survivin, p53 Expressions

Ann Otol Rhinol Laryngol. 2020 Sep;129(9):863-871. doi: 10.1177/0003489420918280. Epub 2020 May 4.

Abstract

Objectives: Tobacco and alcohol are the main etiological factors common to laryngeal cancers. However, the Human Papilloma Virus (HPV) constitutes an alternative risk factor according to several studies. In Tunisia, despite the annual increasing incidence of laryngeal squamous cell carcinoma (LSCC), the prevalence and prognostic significance of HPV have never been explored.In this study, we sought to highlight HPV DNA in 70 biopsies of laryngeal cancer, and to analyze the status of HPV infection in association with p53, p16, survivin, and IGF-1R expressions.

Methods: HPV high risk (HPV HR) DNA was detected in tumors by in situ hybridization. However, the expression of p53, p16, survivin and IGF-1R were stained by immunohistochemistry test. The correlations of HPV status with clinicopathological parameters, overall survival, disease-free survival and proteins expressions were statistically evaluated.

Results: HPV HR DNA was detected in 39 out of 70 (55.71%) laryngeal tumors. HPV+ patients have a better overall survival (P = .081) and long disease-free-survival (P = .016) with a low rate of recurrence (P = .006) than HPV- patients. No significant correlations were found between HPV HR status and clinicopathological parameters (all P > .005). Moreover, HPV+ tumors were not associated with expression of p53, p16 and survivin. However, HPV HR status correlates with weak to moderate IGF-1R expression (P = .043).

Conclusion: The substantial detection of HPV HR in LSCC tumors suggest that this virus plays an important part in laryngeal cancer in Tunisia. It is a good prognostic factor. In addition, HPV infection could act to block the pathway of IGF-1R expression.

Keywords: HPV-HR; IGF-1R; Tunisian patients; laryngeal tumors; prognostic factor; survivin.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis
  • Cyclin-Dependent Kinase Inhibitor p16 / biosynthesis
  • DNA, Viral / analysis
  • Female
  • Humans
  • Laryngeal Neoplasms / chemistry
  • Laryngeal Neoplasms / metabolism
  • Laryngeal Neoplasms / mortality
  • Laryngeal Neoplasms / virology*
  • Male
  • Middle Aged
  • Papillomaviridae / genetics
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / virology*
  • Prevalence
  • Prognosis
  • Receptor, IGF Type 1 / analysis
  • Receptor, IGF Type 1 / biosynthesis
  • Retrospective Studies
  • Survival Rate
  • Survivin / analysis
  • Survivin / biosynthesis
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tunisia

Substances

  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • IGF1R protein, human
  • Survivin
  • Tumor Suppressor Protein p53
  • Receptor, IGF Type 1