In the United States, about 12,900 cases of invasive cervical cancer are diagnosed each year and 50,000 cases of carcinoma in situ are detected by Pap smear. Cervical cancer kills 4100 women a year, 85% of whom never had a Pap smear. It is a major cause of disease in underdeveloped countries and is more common in lower socioeconomic groups, in women with early sexual activity and/or multiple sexual partners, and in smokers. Human papilloma virus (HPV) types 16 and 18 are the major types associated with cervical cancer. The virus attacks the G₁ checkpoint of the cell cycle; its E7 protein binds and inactivates Rb protein, and E6 induces the degradation of p53. Risk factors include a large number of sexual partners, early age at first intercourse, a history of venereal disease, HIV infection, and heavy smoking.