Annual disease burden due to human papillomavirus 16 and 18 infections in Finland

Apart from cancers of the lower female genital tract, human papillomaviruses (HPV) are associated with a large number of benign, premalignant and malignant lesions at different anatomic sites in both genders. Malignant tumours and their precursors are usually attributed to the oncogenic (high-risk, HR) HPV types, whereas benign lesions (mostly papillomas) are ascribed to the low-risk (LR) HPV types, most notably HPV6 and HPV11. To date, the main interest has been focused on HR-HPV types and their associated pathology, and much less attention has been paid to the lesions caused by the LR-HPV types. The recent licensing of an effective prophylactic vaccine against the 2 most important LR-HPV types (HPV6 and HPV11) has resulted in considerably increased interest in these LR-HPV types as well. This author recently conducted a systematic survey of the annual disease burden due to HPV6/11 infections in Finland. As a rational continuation, the present survey was conducted to estimate the annual disease burden due to HPV16 and HPV18 infections in our country. Together, these 2 documents form the foundation for calculations of the annual costs needed to treat the diseases caused by these 2 most common LR and HR HPV types. Similar to HPV6/11, accurate estimates of disease burden are also mandatory for all modelling of the cost-effectiveness of prophylactic HPV16/18 vaccines. In the first step, the published HPV literature was used to create a list of benign, premalignant and malignant lesions associated with this virus at different anatomic sites. The GLOBOCAN 2004 (IARC; International Agency for Research on Cancer) database was used to derive the global numbers of incident cases for each of these malignancies in 2002, and the Finnish Cancer Registry (FCR) website was used to obtain these numbers for Finland (y 2005). The evidence linking HPV to each individual tumour category was classified as: (1) established, (2) emerging, and (3) controversial. All published evidence was weighted for each individual malignant, premalignant and benign lesion, anatomic region-by-region, while assessing the attributable fraction of HPV16/18 genotypes in each lesion. Because benign and most of the precancer lesions are not registered by the FCR or GLOBOCAN, different approaches had to be used to derive the estimates for their incidence, based on published literature or other registries. In cases with no reasonable consensus, a lower and an upper boundary was set for the range of these estimates. Where well established, the different incidence rates among males and females were used to calculate the numbers of incident cases by gender. The present survey implicates that a minimum of 7859 to 8316 new cases of HPV16- or HPV18-associated clinical lesions would be detected each y in Finland, if all were registered. In other words, these numbers represent the annual disease burden due to these 2 most common HR-HPV genotypes. In the Finnish population, these lower and upper limits translate to the crude annual incidence rates of 147/100,000 and 156/100,000, respectively. When adjusted for the European Standard Population, the respective age-adjusted incidence rates are 137/100,000 and 145/100,000. As compared with the annual disease burden of HPV6/11 in this country (12,666-13,066 new cases), these numbers for HPV16/18 are significantly smaller. Another major difference between HPV6/11 and HPV16/18 is that the disease burden due to the former is much more evenly distributed among the genders, with only a slight female preponderance (approximately 7500 vs 5500 cases). This is in sharp contrast to HPV16/18 disease burden, of which by far the major proportion is contributed by females (approximately 7000 vs 1300 cases). Of note, these clinical lesions counted in this report for HPV16/18 only represent a small minority of the total viral burden due to the infections by these 2 HR-HPV genotypes. This is because the vast majority of these HR-HPV infections are transient and spontaneously resolve within a few months, without ever developing a clinical disease. However, this spontaneous clearance does not make these latent infections less important, because as long as the virus reservoir exists, it serves as the source of viral transmission to susceptible individuals, with a multitude of HPV16/18-associated pathologies as a potential outcome. The implications of these data in the era of effective prophylactic HPV vaccination should be straightforward. However, the 2 impending challenges for designers of future HPV vaccines and vaccination programmes are: (1) the marked imbalance of HPV16/18 disease burden between the genders, and (2) the fact that HPV6/11 annual disease burden far exceeds that of HPV16/18 and it is also more evenly contributed by both genders.