Genetic Analysis of Patients with HPV-related and Unrelated Oropharyngeal Squamous Cell Carcinomas and Their Prognostic Implications

Background and Objective: Human papillomavirus (HPV) has been concerned with the pathogenesis of oropharyngeal squamous cell carcinomas (OSCC). OSCC affects about 40,000 persons in the United States each year, regularly involves the oropharynx, oral cavity, larynx, and hypopharynx. Many individuals with oropharyngeal cancer have no common risk factors, and recent epidemiologic and genetic analysis investigations have recognized high-risk types of HPV, especially HPV- 16 as the potential etiologic factors. Patients with HPV containing OSCC have a better prognosis than HPV-negative OSCC patients. Definitely, the connection between HPV and OSCC has increased attention recently. In this study, we analyzed the genetic changes in patients with HPV-related and unrelated OSCC. Materials and Method: We used comparative genomic hybridization to recognize critical genetic alternations in 36 selected OSCC, 16 of which were related to HPV-16 as specified by fluorescence and HPV-definite PCR in situ hybridization and positive p16INK4A immunostaining. The consequences were associated with HPV status and clinical information from patients. Findings: One thirds of OSCC harbored advance at 3q26.3-qter regardless of HPV status. In HPV-negative tumors this change was related to progressive tumor stage (P = 0.011). Compared with HPV-related OSCC, the HPV-negative tumors harbored: (a) meaningfully more losses at 3p, 5q, 9p, 15q and advances at 11q13 (P = 0.003, 0.02; <0.003, 0.01, 0.002, and 0.004, respectively); (b) more changes and amplifications of chromosomes (P = 0.02 and 0.026, respectively). Survival analysis showed a significantly better survival without disease for HPV-related OSCC (P = 0.03), while chromosome amplification was a negative prognostic indicator for survival without disease (P = 0.02 and 0.04, respectively). Remarkably, 16q loss, mainly recognized in HPV-related OSCC, was a potential indicator of promising consequence (overall survival, P = 0.007; survival without disease, P = 0.03) and these patients had no tumor recurrence. Conclusions: Genetic analysis of HPV-related and unrelated OSCC are different and most probably underlie changes in tumor growth and progression. Furthermore, different chromosomal changes have prognostic significance.

کلیدواژه ها:

Human papillomavirus (HPV) ، Oropharyngeal ، Squamous cell carcinomas ، Genetic