Ki67 expression has prognostic significance in relation to human papillomavirus status in oropharyngeal squamous cell carcinoma — ASN Events
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Ki67 expression has prognostic significance in relation to human papillomavirus status in oropharyngeal squamous cell carcinoma (#389)

Jia Jenny Liu 1 2 3 , Mei Zhang 1 2 , Barbara Rose 4 , Anne-Sophie Veillard 5 , Deanna Jones 4 , Soon Lee 6 7 , Angela Hong 1 2
  1. Department of Radiation Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
  2. Central Clinical School, University of Sydney, Sydney, NSW, Australia
  3. Prince of Wales Clinical School and Lowy Cancer Research Centre, University of New South Wales, Kensington, NSW, Australia
  4. Department of Infectious Diseases and Immunology, University of Sydney, Sydney, NSW, Australia
  5. NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
  6. Department of Anatomical Pathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
  7. Bosch Institute, University of Sydney, Sydney, NSW, Australia

Aims:

Human papillomavirus (HPV) is the major predictor of outcome in oropharyngeal squamous cell carcinoma but the disease is heterogeneous and there is limited understanding of the prognostic significance of other molecular markers in relation to HPV. This multi-institutional retrospective study examined the prognostic significance of Ki67 expression in association with HPV status in oropharyngeal squamous cell carcinoma.

Methods:

The 105 patients recruited had a median follow-up of 70 months. Tumour HPV status was determined by HPV E6-targeted multiplex real-time PCR/p16 semiquantitative immunohistochemistry and Ki67 expression by semiquantitative immunohistochemistry. Determinants of recurrence and mortality hazards were modelled using Cox regression with censoring at dates of last follow-up.

Results:

HPV and Ki67 positivity rates were 46% and 44% respectively. HPV-positive cancers were more likely to be Ki67-positive (P=0.015). On univariate and multivariate analysis, HPV positivity was a strong predictor of better outcome. Patients with HPV-positive tumours had better disease-specific (HR 0.27 95% CI 0.11-0.66, P=0.004) and overall survival (HR 0.33 95% CI 0.15-0.70, P=0.004) compared to those with HPV-negative tumours.

Ki67-positive cancers were associated with a 3.1-fold increased risk of disease-related death compared to Ki67-negative cancers (95% CI 1.27 - 7.72; P=0.014). Ki67 status was a predictor of outcome especially in the HPV-negative subgroup. Among HPV-negative patients, Ki67-positivity was associated with 5.6-fold increased risk of disease-related death (95% CI 1.87-16.96, P=0.002), 5.5-fold increased risk of death from any cause (95% CI 2.07-14.62, P=0.001), and 2.9-fold increase in risk of any event (95% CI 1.26-6.76, P=0.013).  

Conclusions:

Ki67 predicts disease-related death in oropharyngeal cancer independent of HPV status. A combination of Ki67 and HPV status provides improved prognostic information relative to HPV alone. Our data suggest for the first time that Ki67 status has prognostic value particularly in HPV-negative oropharyngeal cancer. 

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