HPV genotype distribution in oral and oropharyngeal squamous cell carcinoma using seven in vitro amplification assays

Molecular and epidemiologic evidence indicates that human papillomavirus (HPV) is involved in the etiology of oral and oropharyngeal squamous cell carcinomas (SCCs). HPV(+) tumors appear to be clinically distinct from HPV(-) tumors, conferring improved survival outcomes for patients. Determination of the HPV status of tumors may assist in patient risk-stratification and ultimately guide optimum treatment. The primary aim of this study was to examine the distribution of HPV in oral and oropharyngeal SCCs as assessed using seven different in vitro amplification assays. The secondary aim was to correlate the distribution of HPV in tumors with clinical and demographic patient data.

Sixty-eight invasive oral/oropharyngeal SCCs were tested for HPV using four laboratory-developed PCR assays for HPV16 or 18 and three commercial tests, INNO-LiPA® HPV Genotyping Extra (Innogenetics), Linear Array® HPV Genotyping Test (Roche Diagnostics), and Invader® HPV16/18 ASRs (Hologic Corp.).

Consensus results between tests revealed that 71.9% of tumors were HPV(+), primarily with HPV16 (63.2%). Other genotypes were uncommon and generally occurred coincidently with HPV16. HPV-positivity was significantly higher in oropharyngeal tumors (76.9%), particularly of the tonsils (91.7%), versus oral cavity tumors (20.0%). HPV(+) tumors occurred in younger patients (average 54.4 years versus 61.1 years) and were significantly associated with lower histological differentiation (poorly, 100.0%; moderately, 65.6%; well-differentiated, 42.9%).

A high rate of HPV-positivity, especially involving HPV16, occurred in oropharyngeal tumors, with a lower rate in oral cavity SCCs; however, solitary infections with HPV18, 33 or 45 in a minority of cases signified the potential oncogenicity of these additional genotypes and the likely need to screen for these less common genotypes in clinical specimens.