Detection of partial deletions of the human papillomavirus 16 E6 gene in a subset of oropharyngeal and cervical cancers

Human papillomavirus 16 (HPV16) is a major carcinogenic HPV type responsible for both cervical cancer (CC) and oropharyngeal cancer (OPC). HPV16 E6 polymorphisms vary by geographic region and are correlated with disease progression. Here, we sought to investigate HPV16 E6 variation in Japanese patients and evaluate its clinical relevance. We enrolled 379 patients with CC and OPC, and subjected 100 CC and 71 OPC samples with HPV16 DNA to E6 sequence analysis. The E6 sequence was partially deleted in 13 (13 %) CCs and 16 (23 %) OPCs. Patients with OPC harboring defective E6 had significantly worse overall survival than those with intact E6. This was observed in univariate analysis but not in multivariate analysis when adjusted for viral load. These findings indicate that low viral load is an independent prognostic factor in patients with OPC, and that E6 deletion is associated with low viral load. By contrast, prognostic differences were not observed in patients with CC. In summary, we report a newly identified gene deletion within the HPV16 E6 region associated with low viral load. These findings will facilitate further studies on the clinical and oncological significance of E6 deletion in patients with HPV16-related malignancies.