Human papillomavirus status and p16INK4A expression in patients with mucosal squamous cell carcinoma of the head and neck in Queensland, Australia

• HPV prevalence in Australian HNSCCs and HPV affected cell-cycle regulation.
• Gender and alcohol consumption not associated with HPV or p16 status.
• Predictors of HPV-positivity were younger age (<60 years) and non-moderate smoking.
• High concordance between HPV/p16 status with a kappa of 0.72.
• Despite high concordance, we found 11% being discordant for HPV/p16 status.

BackgroundThe last decade has seen changes in the epidemiology of mucosal squamous cell carcinomas of the head and neck (HNSCCs), with increasing numbers of cases attributable to human papillomavirus (HPV) infection. We sought to determine the prevalence of HPV and p16INK4a expression in Australian HNSCC patients and to identify predictors of HPV-positivity.MethodsWe recruited 248 HNSCC patients with histologically confirmed primary SCC of the oropharynx, oral cavity, hypopharynx or larynx diagnosed between 2004 and 2010. All patients completed a questionnaire. Clinical data were abstracted from medical records. HPV presence in paraffin-embedded tumours was determined by PCR, and expression of p16INK4a, p21WAF1, p53, pRB, cyclin D1, and Ki67 by immunohistochemistry.ResultsFifty (20%) patients were HPV-positive, 63 (28%) overexpressed p16INK4a, and 44 (19%) were positive for HPV and p16INK4a (high concordance between HPV-positivity and p16INK4a status, κ = 0.72). HPV-16 was most common (84%), followed by HPV-18 (10%), HPV-33 (4%) and HPV-69 (2%). HPV and p16INK4a prevalence was highest for SCCs of the oropharynx, followed by hypopharynx, larynx and oral cavity (HPV and p16INK4ap < 0.0001). HPV prevalence and p16INK4a-overexpression were significantly higher in younger than older patients (HPV p = 0.001; p16 INK4ap = 0.003). Heavy smokers had lower HPV prevalence than non- or moderate smokers (p = 0.017). Gender and alcohol consumption were not associated with HPV or p16INK4a status. HPV-positive tumours had significantly lower cyclin D1 and higher p21WAF1 expression than HPV-negative tumours.ConclusionHPV prevalence and p16INK4a-overexpression were highest in oropharyngeal tumours, younger patients, and non-smokers.