HPV and Other Cofactors in Cervical Cancer
Division of Cancer Epidemiology, McGill University, Montreal, Canada
The epithelial lining of the anogenital tract is the target for infection by a group of mucosotropic viruses, the human papillomaviruses (HPV). HPVs are DNA viruses with a genome of approximately 8000 base pairs. There are more than 150 HPV types defined via DNA homology, of which more than 40 infect the anogenital tract. HPVs are the most common sexually-transmitted agents, affecting 10%-40% of sexually active women, in an age-dependent fashion. Cervical cancer and most epithelial malignancies of the anogenital tract are caused by about 15 HPV types that have oncogenic properties, HPV 16 being the most common among them. The relative risks of cervical cancer following HPV infection as ascertained in case-control and cohort studies are among the highest in cancer epidemiology. The available evidence indicates that the HPV-cervical cancer association satisfies all relevant causal criteria for public health action. Virtually all cervical carcinoma specimens contain HPV DNA, which suggests that HPV infection is a necessary cause of cervical neoplasia. This is the first instance in which a necessary cause has been demonstrated in cancer epidemiology -- a realization that has obvious implications for primary and secondary prevention of this neoplastic disease. On the other hand, HPV infection alone is not a sufficient cause of progression to cervical malignancy. Other risk factors, such as smoking, parity, oral contraceptives, diet, other infections, and host susceptibility markers also influence cervical carcinogenesis. The role of these variables has to be understood in the context of mediation of acquisition of HPV infection or in influencing events of the natural history of cervical neoplasia that occur following the establishment of a persistent HPV infection.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in plenary session 801 (Predictive markers & validation).