Better still, a vaccine has now been developed that protects against infection with the relevant strains of human papillomavirus. This vaccine, given to girls before puberty and thus before they become sexually active, has been shown to greatly reduce their risk of ever developing cervical cancer. Because the virus spreads through sexual activity, it is now recommended that both young males and young females be routinely vaccinated. Mass immunization programs have begun in several countries.
Figure 20–40 How certain papillomaviruses are thought to give rise to cancer of the uterine cervix. Papillomaviruses have double-stranded circular DNA chromosomes of about 8000 nucleotide pairs. These chromosomes are normally stably maintained in the basal cells of the epithelium as plasmids (red circles), whose replication is regulated so as to keep step with the chromosomes of the host. (A) Normally, the virus perturbs the host cell cycle only when the virus is programmed to produce infectious progeny, in the outer layers of an epithelium. This is relatively harmless.
(B) Rare accidents can cause the integration of a fragment of such a plasmid into a chromosome of the host, altering the environment of the viral genes in the basal cells of an epithelium. This can disrupt the normal control of viral gene expression. The unregulated production of certain viral proteins (E6 and E7) interferes with the control of cell division in the basal cells, thereby helping to generate a cancer (bottom).
viral proteins mediate the controlled replication of the virus in outer cell layers unregulated production of viral proteins drives cell proliferation in basal cell layer
Infectious Agents Can Cause Cancer in a Variety of Ways
In papillomaviruses, the viral genes that are mainly to blame are called E6 and E7. The protein products of these viral oncogenes interact with many host-cell proteins, but, in particular, they bind to two key tumor suppressor proteins of the host cell, putting them both out of action and so permitting the cell to replicate its DNA and divide in an uncontrolled way. One of these host proteins is Rb; the other is p53. Other DNA tumor viruses use similar mechanisms to inhibit Rb and p53, underlining the central importance of inactivating both of these tumor suppressor pathways if a cell is to escape the normal constraints on proliferation.
In other cancers, viruses have indirect tumor-promoting actions. The hepatitis-B and C viruses, for example, favor the development of liver cancer by causing chronic inflammation (hepatitis), which stimulates an extensive cell division in the liver that promotes the eventual evolution of tumor cells. In AIDS, the human immunodeficiency virus (HIV) promotes development of an otherwise rare cancer called Kaposi’s sarcoma by destroying the immune system, thereby permitting a secondary infection with a human herpesvirus (HHV-8) that has a direct carcinogenic action. By causing severe inflammation, chronic infection with parasites and bacteria can also promote the development of some cancers. For example, chronic infection of the stomach with the bacterium Helicobacter pylori, which causes ulcers, appears to be a major cause of stomach cancer; dramatic falls in the incidence of stomach cancer over the last half-century (see Figure 20–39) correlate with a decline in the incidence of Helicobacter infections.
The Search for Cancer Cures Is Difficult but Not hopeless
The difficulty of curing a cancer is similar to the difficulty of getting rid of weeds. Cancer cells can be removed surgically or destroyed with toxic chemicals or radiation, but it is hard to eradicate every single one of them. Surgery can rarely ferret out every metastasis, and treatments that kill cancer cells are generally toxic to normal cells as well. Moreover, unlike normal cells, cancer cells can mutate rapidly and will often evolve resistance to the poisons and irradiation used against them.