Impact of human papillomavirus (HPV) E6/E7 gene silencing on the expression of biomarkers that distinguish HPV+ versus HPV16- head and neck squamous cell carcinomas (HNSCC)

e17024 Background: Three studies (Pyeon et al, Slebos et al, and Schlecht et al) have identified biomarkers that distinguish HPV+ versus HPV- HNSCC using cDNA microarrays. We sought to determine whether the identified biomarker differences are a direct consequence of HPV16 E6 andE7 oncogene expression. Methods: We selected genes that were found to have altered expression in HPV16+ HNSCC compared to HPV16-. Short hairpin RNAs targeting HPV type 16 E6 and E7 genes were delivered by retrovirus infection to HPV16+ oropharyngeal cancer cell lines 147T and 090. cDNA microarray analysis was performed (slides represented approximately 35000 genes) to determine the transcriptional profile before and after E6/E7 silencing. Results: E6/E7 gene silencing affected the expression of the following genes: RFC4, CDKN2A, MCM6, NASP, EP300, E2F2, PCNA, KLK6, ANGPT1, DNAJCI, PRKCG (Table). Conclusions: Expression of several biomarkers that distinguish HPV16+ from HPV16- HNSCC is regulated by E6/E7 gene expression. Targeting E6/E7 will be an effective therapeutic strategy in HPV16+ HNSCC since alteration of key molecules that increase the malignant potential of these tumors is controlled by E6/E7 expression. [Table: see text] No significant financial relationships to disclose.