BACKGROUND: Although years of potential life lost (YPLL) and mortality-related productivity costs comprise a substantial portion of the burden of cancers where human papillomavirus (HPV) may be a risk factor for carcinogenesis (called HPV-associated cancers in this report), estimates of these costs are limited. The authors estimated the mortality-related burden (in terms of YPLL and productivity costs) of HPV-associated cancers (without regard to the percentage of each of these cancers that could be attributed to HPV) and all malignant cancers in the United States in 2003. METHODS: The authors used 2003 national mortality data and US life tables to estimate YPLL for HPV-associated cancers and all malignant cancers. YPLL was estimated by using the life expectancy method. The human capital approach was used to estimate the value of the expected future lifetime productivity losses caused by premature deaths from HPV-associated cancers and all malignant cancers. Indirect mortality costs were estimated as the product of the number of deaths and the expected value of individuals' future earnings, including an imputed value of housekeeping services. RESULTS: In 2003, HPV-associated cancers accounted for 181,026 YPLL, which represented 2.4% of the estimated 7.5 million YPLL attributable to all malignant cancers in the United States. The average number of YPLL was 21.8 per HPV-associated cancer death and 16.3 per death from overall malignant cancers. Overall, HPV-associated cancers had the largest relative contribution to YPLL in women ages 30 to 34 years. The lifetime productivity cost from mortality in 2003 was $3.7 billion for HPV-associated cancer mortality and $133.5 billion for overall malignant cancer mortality. CONCLUSIONS: HPV-associated cancers impose a considerable burden in terms of premature deaths and productivity losses.