Epidemiological and laboratory evidence indicate that, in addition to tobacco and alcohol, human papillomaviruses (HPV) play an important aetiological role in a subset of
head and neck squamous cell carcinoma (
HNSCC). To evaluate the molecular pathogenesis of HPV-infected
HNSCC, we compared gene expression patterns between HPV-positive and -negative
HNSCC tumours using
cDNA microarrays. Tumour tissue was collected from 42 histologically confirmed
HNSCC patients from an inner-city area of New York. Total
DNA and
RNA were extracted and purified from frozen tumour samples and gene expression levels were compared to a universal human reference
RNA standard using a 27 323
cDNA microarray chip. HPV detection and genotyping were performed using an MY09/11-PCR system and RT-PCR. HPV was detected in 29% of
HNSCC tumours. Most harboured only HPV16 and expressed the HPV16-E6 oncogene. HPV prevalence was highest in pharyngeal tumours (45%). Gene expression patterns that differentiated HPV-positive from negative tumours were compared by supervised classification analysis, and a multiple-gene signature was found to predict HPV16 prevalence in primary
HNSCC with a false discovery rate < 0.2. Focusing on never-smokers, we further identified a distinct subset of 123 genes that were specifically dysregulated in HPV16-positive
HNSCC. Overexpressed genes in HPV-positive
HNSCC tumours included the
retinoblastoma-
binding protein (p18),
replication factor-C gene, and an E2F-dimerization partner
transcription factor (TFDP2) that have also been found to be overexpressed in
cervical cancer. An additional subset of genes involved in viral defence and immune response, including
interleukins and
interferon-induced
proteins, was found to be down-regulated in HPV-positive tumours, supporting a characteristic and unique transcriptional profile in HPV-induced
HNSCC.