The IARC Commitment to Cancer Prevention: The Example of Papillomavirus and Cervical Cancer

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Abstract
Every year approximately half a million women worldwide develop cervical cancer (CC) of whom 80% live in poor countries where population-based screening programmes are virtually non-existent. The role of sexually transmitted agents in the aetiology of cervical cancer has been suspected for more than a century, but knowledge in this field has rapidly expanded only in the last 20 years, after major improvements were made in detection methods for human papillomavirus (HPV). A dozen types of HPV have been identified in 99% of biopsy specimens from CC worldwide and the relative risk estimates for HPV in case-control studies of CC are in the 50 to 100 range. A meta-analysis done at the International Agency for Research on Cancer (IARC) included a total of 10,058 CC cases from 85 published studies. The most common HPV types identified in CC were, in order of decreasing prevalence, HPV 16, 18, 45, 31, 33, 58, 52, 35, 59, 56, 6, 51, 68, 39, 82, 73, 66 and 70. Over two-thirds of CC cases were associated with an infection of either HPV 16 (51.0%) or HPV 18 (16.2%). Despite the overwhelming importance of HPV, other factors contribute to the rare occurrence of CC after HPV infection. Nine case-control studies from the IARC have confirmed the adverse effect of long-term use of oral contraceptives, high parity, smoking and sexually transmitted infections (i.e. Chlamydia trachomatis and herpes simplex virus-2) after adjustment for, or stratification by, HPV infection. Ten surveys of HPV infection in population-based samples of approximately 15,000 women in four continents have shown that: (1) the prevalence of HPV infection varies greatly (between 2% and nearly 30%); and (2) the age distribution also varies widely, pointing to cohort effects. There is no effective medical treatment for HPV, but a prophylactic vaccine, based on late (L) 1 HPV 16 proteins, has been shown to be safe, highly immunogenic and efficacious in preventing persistent HPV infections. A multivalent vaccine against the most common oncogenic HPV types may thus ultimately represent the most effective way to prevent CC worldwide either alone, or in combination with screening. It may, however, take several years before this approach becomes a reality. Thus, early detection of CC precursor lesions by screening, and their treatment, will remain the most important measures for the control of CC for the foreseeable future.