Infection with certain viruses can also result in cell transformation, stable genetic changes in the cell that result in disregulated cell growth and extended growth potential (immortalization). In animals, such virally induced cellular changes can result in cancer. This correlation was first made by Harry Rubin and Howard Temin in the 1950s, when they observed that Rous sarcoma virus, a retrovirus capable of inducing solid tumors in chickens, could also cause biochemical and structural changes and extend the proliferative potential of cultured chicken cells.
Viruses are perhaps second only to tobacco as risk factors for human cancers. DNA tumor viruses include papillomaviruses and various herpes viruses (such as HHV-8, which causes Kaposi's sarcoma). More than sixty strains of human papillomaviruses (HPV) have been identified. HPV cause warts, which are benign tumors, but are also the causes of malignant penile, vulval, and cervical cancers. Infection with hepatitis B or C viruses is associated with increased incidence of liver cancer. Adenoviruses have been shown to induce cancers in animals, but not in humans. Retroviruses can also cause cancer in various animal species, including humans. HTLV-1 causes adult T-cell leukemia in about 1 percent of infected humans.
Viruses can cause cancer through their effects on two important cellular genes or gene products: tumor suppressors and oncogenes. These genes are critical players in cell-cycle regulation. One protein product from HPV binds to the retinoblastoma (Rb) tumor suppressor protein. HPV E6 protein binds p53 tumor suppressor protein and promotes its degradation. Acutely transforming retroviruses, which induce tumors in a short time period of weeks to months, carry modified versions of cellular oncogenes, called viral oncogenes. Slowly transforming retroviruses also subvert cellular oncogenes, but by integrating into or near the oncogene, thereby altering its expression, a process that can take years because of the apparently random nature of retrovirus integration.