Human papillomavirus in oropharyngeal squamous cell carcinomas in Korea: use of G1 cycle markers as new prognosticators

Head Neck. 2012 Oct;34(10):1408-17. doi: 10.1002/hed.21939. Epub 2011 Nov 2.

Abstract

Background: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC) exhibits distinct patterns worldwide, but its prevalence has not been extensively evaluated in Korea. The E7 oncogene-mediated carcinogenesis and its meaning are yet to be uncovered for oropharyngeal SCCs.

Methods: In a Korean oropharyngeal SCC cohort, epidemiological indicators, HPV, and G1 cell cycle marker expressions were correlated with survival.

Results: Among 93 surgically treated patients with oropharyngeal SCCs, 49.5% were HPV+, which were significantly younger, and predominantly nonsmoking. They demonstrated better survival than HPV- (94% vs 60%). Patients who were HPV+ with oropharyngeal SCCs expressed higher p16, cyclin-dependent kinase 4 (cdk4), and lower pRb. The p16 (hazard ratio [HR] 2.39), pRb (HR 2.13), and CCND1 (HR 2.09) correlated with survival. Notably, combined markers like p16/cdk4 ratio (HR 2.47) and cdk4+CCND1 sum (HR 2.65) were more significantly correlated.

Conclusion: Incidence of HPV-related oropharyngeal SCC in Korea is similar to U.S.-European data. HPV presence correlates with improved survival. Expression ratios of G1 markers may predict survival of oropharyngeal SCCs better than each marker alone.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Biomarkers, Tumor / metabolism*
  • Biopsy, Needle
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / virology
  • Cell Cycle / genetics
  • Cohort Studies
  • Comorbidity
  • Confidence Intervals
  • Cyclin D1 / metabolism*
  • Cyclin-Dependent Kinase 4 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral / analysis
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Korea / epidemiology
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism
  • Neoplasm Recurrence, Local / epidemiology
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Oropharyngeal Neoplasms / metabolism*
  • Oropharyngeal Neoplasms / mortality*
  • Oropharyngeal Neoplasms / pathology
  • Oropharyngeal Neoplasms / surgery
  • Oropharyngeal Neoplasms / virology
  • Papillomaviridae / genetics
  • Papillomaviridae / metabolism
  • Papillomavirus Infections / mortality
  • Polymerase Chain Reaction / methods
  • Prevalence
  • Prognosis
  • Proportional Hazards Models
  • Regression Analysis
  • Retrospective Studies
  • Risk Assessment
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • CCND1 protein, human
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • Neoplasm Proteins
  • Cyclin D1
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4