Chapter 1: Human papillomavirus and cervical cancer--burden and assessment of causality.

Cervical cancer remains the second most common cancer in women worldwide and the most frequent in developing countries. Pre-neoplasic cervical lesions represent an additional burden in countries where screening is widespread. The human papillomavirus (HPV) prevalence and type distribution in normal smears and in cancer specimens are being described and show relatively small international variation. State-of-the-art detection techniques have unequivocally shown that HPV-DNA can be detected in 95% to 100% of adequate specimens of cervical cancer, supporting the claim that HPV is the necessary cause. The odds ratios for cervical cancer related to a cross sectional detection of HPV-DNA range from 50 to several hundred in all studies. The risk for any of 15 high-risk types is not statistically different from the risk reported for HPV16. The estimates of the attributable fraction range from 90% to 98%. Additional work should be done in providing information on incidence of cervical cancer and on HPV infection in areas where the disease is common. Theoretical work including modeling of the incidence could be of potential use in the evaluation of the existing and novel preventive strategies. Research is currently being conducted on the mechanisms of HPV carcinogenesis. These include the determinants of the systemic and cellular immune response to the viral infection, the interaction between the host and the virus and the relevance of the different strains and variants of the HPV viral types. Technology developments in this area suitable for epidemiological studies are needed.