Despite formidable data gaps, our review of secondary data and estimation of the direct medical costs associated with 7 HPV-related conditions demonstrate a substantial economic burden imposed by HPV-attributable noncervical disease in the United States. Using an incidence-based approach, the economic burden associated with noncervical HPV-related conditions occurring in Americans in the year 2003 approximates $418 million. This figure has a considerably wide plausible range of $160 million to $1.6 billion, which is driven predominantly by the substantial uncertainty in the cost of JORRP and the incidence of JORRP and anogenital warts.
Two vaccines against HPV-16 and -18 have been found to be highly efficacious against same type incidence and precancerous lesions of the cervix, vagina, and vulva among females without indication of prior infection with these types; and the quadrivalent vaccine currently licensed in the U.S. also prevents infection with HPV-6 and -11, responsible for of the majority of genital warts and JORRP. [5
] Given these options for primary prevention of HPV-related disease, along with enhanced screening approaches for secondary prevention of HPV-related cervical cancer, there is considerable interest in comparative assessments of the health and economic consequences associated with alternative strategies to reduce the burden of HPV-related disease. Accordingly, we provide a comprehensive estimate of the economic burden of noncervical HPV-related disease in the U.S. Although we consider this figure to be an approximate estimate at best, nonetheless, our results highlight the significant cost dimensions of this health problem and the importance of preventing these conditions to reduce both the health and economic burden of HPV infection. The estimated costs associated with each HPV-related condition can be used in future economic evaluations of HPV vaccination, and the lower and upper bound estimates as the plausible range for sensitivity analyses.
Our study has several limitations which merit acknowledgement. First, sources of cost data were limited and the quality of available information was variable. For example, much of the data used to derive lifetime cost per case estimates were not comprehensive. Many estimates included only selected aspects of care such as diagnosis and treatment and omitted costs related to staging, surveillance, or recurrence. In these instances, cost per case figures likely underestimate the actual lifetime cost of disease. In addition, sources of cost information ranged from private health insurance to Medicare claims, each of which is associated with its own inherent flaws and biases [7
]. Second, we did not consider nonmedical direct or indirect costs such as transportation costs to healthcare facilities or the value of work time lost receiving health care. Studies addressing these types of costs are unavailable for noncervical HPV-related conditions [7
]. Incorporation of these costs would make the economic burden of noncervical HPV-attributable disease even higher. Third, other HPV-attributable conditions such as vulvar, vaginal, penile, and anal intraepithelial neoplasia were not included in our burden analysis. However, since there are no screening recommendations for these conditions and the fraction of cases attributable to HPV is unknown, the contribution of these conditions to the total HPV cost burden is also unknown. Fourth, the population attributable fraction of noncervical cancers to HPV is uncertain. Because HPV is highly prevalent in healthy subjects, this method may overestimate the fraction of cancers to attributable HPV infection [3
]. Finally, there was considerable uncertainty surrounding the cost of JORRP and the incidence of JORRP and anogenital warts. Since these two conditions may account for more than 60% of the economic burden of noncervical HPV disease, we feel refinement of these estimates to be of particularly high priority for future research studies.
Directly comparable estimates of the total economic burden of noncervical HPV-related disease associated with incident cases over a one-year period are not available. Prior studies have focused primarily on individual facets of this health problem such as anogenital warts or JORRP [6
]. We were unable to identify any published estimates of the total lifetime direct medical cost of anal, penile, vaginal, or vaginal cancer. This may be due to the fact that these cancers are relatively uncommon. As a result, economic burden data for HPV have been largely confined to cervical disease [6
] and likely represent an underestimate of the economic burden posed by HPV infection.
Quantification of the cost dimensions of noncervical HPV-attributable disease is important because it offers insight into not only the overall economic magnitude but also the relative contribution of different HPV-related conditions. For example, while cervical disease is responsible for the majority of the cost burden associated with HPV- related disease, the contribution of noncervical disease is still considerable, with our base case estimate representing nearly 9% of the total economic burden when incidence-based estimates are used [6
]. Among the noncervical HPV-attributable conditions, anogenital warts contribute to the largest fraction of the total burden, followed by anal cancer and JORRP. In fact, non-cancerous conditions due to HPV 6 and 11 (JORRP and anogenital cancer) are responsible for more than 60% of the total economic burden of noncervical HPV-related disease. Such information may be useful to policymakers and public health researchers to inform decisions about investments in potential HPV prevention programs.
In summary, our results demonstrate the substantial economic burden imposed by HPV-attributable noncervical disease in the U.S. Future research priorities should include refinement of cost estimates for noncervical HPV-related conditions, the incidence of JORRP and anogenital warts, and the population HPV-attributable fraction of noncervical conditions.