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Human papillomavirus and oropharyngeal cancer in British Columbia

University of British Columbia

Oropharyngeal squamous cell carcinoma (OpSCC) patients have improved survival when tested positive for high-risk human papillomavirus (HR-HPV). However, tissue assessment of HPV status is currently not standardized and additional factors may influence survival among HPV-positive patients. The main objectives were to evaluate HPV detection methods and to identify possible factors that impact survival of OpSCC patients in British Columbia. We retrospectively analyzed 972 primary OpSCC patients diagnosed between 2000-2008 and referred to the BC Cancer Agency for treatment with curative intents of radiotherapy with or without concurrent chemotherapy. Patient charts were reviewed and collected information for demographics, smoking history, clinical assessments, treatment received, and outcomes. We analyzed two cohorts of Study Cohort, 244 cases with enough formalin-fixed, paraffin-embedded (FFPE) tissues for experiment, and General Cohort, 728 cases without tissues available. Experimental procedures included in situ hybridization (ISH) to detect DNA and RNA HPV and immunohistochemistry (IHC) to detect p16, p53, the retinoblastoma protein (pRB), cyclin D1, and Ki67. We used polymerase chain reaction (PCR) to detect type-specific HPV from cases with enough FFPE tissues for DNA extraction (n=41). Cox proportional hazard (Cox-PH) and Kaplan-Meier (KM) survival analysis were conducted to identify potential clinical and biological factors impacting on 5-year overall survival (OS), disease-specific survival (DSS), and development of loco-regional recurrence (LRR). The incidence rates of males increased from 3.2 to 7.6 per 100,000 whereas females declined from 1.1 to 0.8 per 100,000. The Study Cohort was relatively representative of the General Cohort. The Study Cohort of patients classified as ever-smokers, had tumours staged at T3/4, and received radiotherapy only had poorer 5-year OS, DSS, and LRR (p<0.05). HPV was detected in 77.6% of patients. Using PCR as standard, DNA/RNA ISH to detect HPV was more specific than IHC p16. Stratification of patients by HPV status showed that HPV-positive/p53-positive and HPV-negative/cyclin D1-positive patients had significantly poorer DSS (p=0.03) and 5-year OS (p=0.02), respectively. In conclusion, both HPV burden and its prognostic significance were found in BC. ISH assessment may be used to determine HPV status. IHC assessments of p53 or cyclin D1 status may be prognostic indicators to guide treatment.

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2018-04-20

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/65545

Craniofacial Science

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/