Cancer registries and monitoring the impact of prophylactic human papillomavirus vaccines: The potential role

More than 5% of cancers worldwide are attributable to human papillomavirus (HPV) infection, and the greatest attributable fraction is associated with cervical cancer.1 Globally, an estimated 250,000 women die each year of cervical cancer. Prophylactic vaccines against oncogenic types of HPV, which became available to the US market in 2006, hold the promise of becoming a public health triumph in the 21st century. It will be at least 1 to 3 decades after the vaccine becomes available before the population targeted for vaccine (in the United States, this includes girls ages 11–12 years) will be at risk for important endpoints of HPV infection, namely, cervical intraepithelial neoplasia 3 (CIN-3), carcinoma in situ (CIS), and invasive cervical carcinoma (ICC). The biology of HPV infection and its role as the primary cause of cervical cancer is well established.2–4 Essentially all cervical carcinomas are caused by persistent infection with 1 of 13 to 15 oncogenic HPV types.2–4 Preventing HPV type 16 (HPV-16) and HPV-18 infections could eliminate >70% of all cervical carcinomas, assuming that, as predicted, that there is no type replacement and that other types remain less likely to progress to carcinoma.5,6 Clinical trials evaluating prophylactic HPV vaccines directed specifically against HPV-16 and HPV-18 have reported nearly complete efficacy for preventing type-specific HPV persistence and related cervical, vaginal, and vulvar cancer precursors among adolescent and young women who were naive to the vaccine type and who completed the full 3-dose schedule.7–9 However, the vaccines were not effective in preventing progression to disease among women who already were infected. It has been estimated that vaccination against HPV-16 and HPV-18 would reduce cytologic reports of high-grade squamous intraepithelial lesions by 50% and would have a more modest impact on less severe diagnoses.4 The effectiveness of vaccine in actual use (ie, not in clinical trials) has yet to be determined, and many challenges exist. These effectiveness data are needed to assess the true public health benefit of HPV vaccination. A key approach to determining the public health benefit and cost-effectiveness of the prophylactic HPV vaccine in the United States is implementation of population-based surveillance activities. In October 2006, the Pan American Health Organization (PAHO) convened experts to discuss the most appropriate and effective strategies for conducting surveillance of the HPV vaccine10 (see Table 1). Surveillance outcomes proposed by the PAHO expert committee included monitoring changes in ICC incidence and mortality and determining trends in the type-specific prevalence and incidence of histologic confirmed CIN-3 lesions. In August 2006, experts convened at the Centers for Disease Control and Prevention (CDC) (Atlanta, Ga) discussed the importance in monitoring the impact of the HPV vaccine in the United States and judged high-grade CIN as the most important cervical cancer precursor endpoint for monitoring purposes. Recommendations from both meetings included outcomes that 1) currently are being collected by US cancer registries and health departments (ICC incidence and mortality), 2) were collected in the past by US cancer registries (CIS; CIN-3), and 3) have the potential to be collected through special projects (HPV type distribution associated with CIN-3, ICC, and noncervical cancers). TABLE 1 Results From an Ad Hoc Meeting Conducted by the Pan American Health Organization on Important Biologic Endpoints for Human Papillomavirus Vaccine Surveillance The US population-based cancer registries include the CDC’s National Program of Cancer Registries (NPCR) and the National Cancer Institute’s (NCI’s) Surveillance, Epidemiology, and End Results (SEER) Program. Together, these registries cover 100% of the US population and serve an essential public health function through the collection and compilation of cancer incidence data that are used for cancer prevention and control efforts and guidance of public health policy.11 The infrastructure to conduct population-based surveillance for the HPV vaccine already is in place through the registries, and they provide a unique opportunity to build upon already existing programs to conduct enhanced HPV-associated precancer and cancer surveillance. These efforts will require a well funded, carefully organized national effort guided by a multidisciplinary team of experts. In this report, we provide a perspective on the potential role of the US population-based cancer registries in monitoring the effectiveness of prophylactic HPV vaccines beyond their current role of collecting data and monitoring the occurrence of cancers. In addition to discussing the merits of and challenges for using cancer registries for the surveillance of trends in the incidence of HPV-associated disease, we also consider resources that will be needed to implement and sustain these types of surveillance activities within the cancer registry system.