Reference Manual - IARC Screening Group

Human Papillomavirus and Cervical CancerDNA testing, which is now commercially available, scientists haveidentified nearly 100 types of papillomavirus—more than 40 of whichpreferentially infect the genital area (Wright et al. 2006). It remainsunknown, however, why certain types of HPV target the skin on thehands or feet while others attack the lining cells of the mouth, and stillothers the genitalia of both men and women (Terai et al. 1999).A link between HPV infection and cervical cancer was first demonstratedin the early 1980s. The 40 papillomavirus types that preferentially infectthe genital area infect primarily the cervix, vulva and vagina in women; thepenis in men; and the urethra and anus in both sexes. Of these types, onlyfour are most often found within cervical cancer cells (so-called “high-risk”types), with type 16 accounting for about half of the cases in the UnitedStates and Europe. In Latin America, by contrast, types 39 and 59 are themost prevalent, whereas type 45 is common in West Africa (Groopman1999; Stewart et al. 1996). And, as mentioned previously, HPV is presentin virtually all cases of cervical cancer (Walboomers et al. 1999). There areseveral commercially available tests for the presence of HPV DNA indeveloped and in some developing countries. While they are reasonablysensitive and specific (see Appendices A and B) for detection of cervicalprecancer, the tests are relatively expensive and beyond what manydeveloping countries can afford.HOW HPV INDUCES CANCERCervical cancer is probably one of the best-known examples of howinfection with a virus can lead to cancer. In humans and animals, celldivision is regulated largely by two proteins—one called Rb and theother p53. Recently it has been found that two genes in HPV, the socalled E6 and E7 genes, produce proteins that can attach themselves toRb and p53 and block their effect on regulating cell division (Massimiand Banks 1997). When this effect is blocked, the infected cellsreproduce without any control. Although the virus serves only as theinitiating event, over time some of the wildly growing cells developpermanent changes in their genetic structure that cannot be repaired, andare closely associated with the development of precancer. Once thesegenetic changes occur, some may eventually turn into cancer cells.Importantly, the affected cells also produce abnormal proteins, and theseproteins can be found in both the cervical secretions and in thecirculation, which has implications for development of future tests.In the early stages, virus-infected cervical cells may show only smallchanges in size and shape when examined microscopically. With time,however, not only do the cells expand and become more distorted, buttheir neat arrangement in rows or columns on the surface of the cervix isdestroyed. These changes are consistent with those of cervical dysplasiaor CIN of varying degrees of severity, as seen by the pathologist whenCervical Cancer Prevention Guidelines for Low-Resource Settings 2-3