The Tango and Tangle of Human Papillomavirus and the Human Genome

Extract

Human papillomavirus (HPV) oncogenic types, especially type 16, are some of the most potent human carcinogens described. The odds ratio of squamous-cell cancer in HPV16-infected women has been estimated to be 435 (95% confidence interval [CI] = 278 to 679) and appears to be high throughout the world ( 1 ) . The public health burden of both HPV and cervix neoplasia is profound; cervical cancer is the second most prevalent cancer in the developing world with nearly half a million cases diagnosed per year ( 2 ) . In contrast, the risk of lung cancer associated with cigarette smoking varies throughout the world, with odds ratios of 4.0 and 40.0 in Japan and United States, respectively ( 3 ) .

The final link in the etiologic trail of HPV and cervical cancer is about to be tested. The availability and widespread use of prophylactic vaccines for HPV16 and HPV18 ( 4 ) , with an anticipated two-thirds reduction in cervical cancer incidence in vaccinated women, will be the final fulfillment of Hill's criteria, as previously discussed ( 5 ) . Nevertheless, HPV infection and cervical cancer will remain a major health burden for decades to come. Studies on the molecular basis and viral–host dynamics of HPV-associated disease will continue to contribute to clinical screening and management strategies, as well as to models of solid tumor pathogenesis. Moreover, in the upcoming HPV vaccine era, it will be important to understand the modes of HPV evolution and adaptation to immunized hosts. In this issue of the Journal, the study of Xi et al. ( 6 ) provides insights into the ability of the most clinically relevant HPVs to evolve over a relatively short evolutionary period.