VRBPAC Briefing Document Presented by Merck on 17 November 2010
Human papillomaviruses (HPV) cause a significant burden of benign and malignant anogenital disease in men and women. The HPV-related anogenital cancers all develop through a common pathogenetic process of neoplastic change that begins with the necessary event of HPV infection. After cervical cancer, the anogenital malignancy with the strongest overall causal relationship to HPV is anal cancer, which affects both men and women. Like the other HPV-related cancers, anal cancer is primarily related to high-risk HPV types 16 and 18 and is preceded by high-grade intraepithelial neoplasia (highgrade anal intraepithelial neoplasia, high-grade AIN, or AIN 2/3), which is widely accepted as its precursor lesion. The incidence of anal cancer in the United States is increasing in men and women, with a higher incidence rate in women compared to men. Despite the growing number of individuals affected by anal cancer, there is currently no preventive measure and no standard screening for anal cancer in the general population. Prevention of anal cancer is thus an unmet medical need. The Protocol 020 AIN efficacy study was designed to evaluate the potential of GARDASIL® to address this unmet need.