OBJECTIVES:  Although years of potential life lost (YPLL) and mortality-related productivity costs comprise a substantial portion of the burden of cancers where HPV may be a risk factor for carcinogenesis (henceforth called HPV-associated cancers), estimates of these costs are limited. We estimated the mortality-related burden (in terms of YPLL and productivity costs) of HPV-associated cancers and all malignant cancers in the United States in 2003. METHODS: We used 2003 national mortality data and US life tables to estimate YPLL for HPV-associated cancers and all malignant cancers. YPLL was estimated by use of the life expectancy method. We used the human capital approach to estimate the value of the expected future lifetime productivity losses due to 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 in YPLL, which represent 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 to overall malignant cancers. Overall, HPV-associated cancers had the largest relative contribution to YPLL in 30–34 year-old females. The lifetime productivity cost due to 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. Quantifying the burden of these HPV-associated cancers mortality in the population may provide useful information for understanding the full potential benefits of prevention efforts.