Genomics of cervical cancer and the role of human papillomavirus pathobiology.

Cervical cancer represents one of the most common malignancies in women worldwide and predominantly affects women of poor socioeconomic status. Persistent infection with high-risk human papillomavirus (HPV)3 is an essential factor for development of cervical cancer. HPV infection is also associated with cancers of the vulva, vagina, anus, and oropharynx. Globally, an estimated 610 000 (4.8%) of the 12.7 million new cancer cases that occurred in 2008 could be attributed to HPV infection, and >500 000 of those cases represent cancers of the cervix alone (1). Within the last 2 decades, research has culminated in major advances in techniques for cervical cancer screening using HPV DNA and has led to a vaccine to prevent HPV infection. Yet, our strategies for the care and treatment of today's patients already infected with HPV need urgent attention. Women diagnosed with invasive and metastatic cervical cancer are in critical need of more-sophisticated prognostic markers, targeted therapeutic options, and more-accurate surveillance strategies. There are about 120 HPV types, and types 16 and 18 are associated with 70% of the cases of cervical cancer worldwide. Many studies have shown that HPV-18–associated cervical cancer is a strong independent prognostic factor for poorer disease-free survival for women undergoing surgery or radiation for early-stage invasive cervical cancer (2). The biology behind the poorer outcomes is unknown, but studies have suggested that sequence variation in HPV genes produces differences in their oncogenic potential. For example, HPV-18 E6 4 (E6 transforming protein) oncogene variants differentially regulate members of the Akt/P13K pathway and show increased expression of genes involved in cancer cell extravasation and metastasis (3, 4). HPV integration into the host genome is a critical step in cervical carcinogenesis and is found in almost all invasive cervical cancers. Integration frequently disrupts HPV E2 (E2 regulatory protein) gene expression, …