Targeting EGFR in HPV-Associated Cancer.

Squamous cell carcinoma of the cervix, anal canal, and hypopharynx is known to be associated with human papilloma virus (HPV) infection. HPV is a double-stranded DNA virus that encodes oncogenic proteins, including E5, E6, and E7. E5 activates epidermal growth factor receptor (EGFR) by binding to its 16 kDa subunit of protein pump ATPase, thereby promoting proto-oncogene expression, inhibits the expression of the tumor suppressor gene p21, and amplifies mitogenic EGFR signals. In addition, E6 and E6 proteins bind to p53 and pRb, respectively, resulting in reduced levels and function of p53 and pRb within the cell, thereby inhibiting apoptosis and promoting genomic instability. EGFR-directed therapies are effective treatments for squamous cell carcinoma of the head and neck and are also being evaluated in other HPV-associated tumors. [ABSTRACT FROM AUTHOR]