Annual disease burden due to human papillomavirus (HPV) 6 and 11 infections in Finland

Abstract

In addition to cancer of the lower female genital tract, human papillomaviruses (HPV) are associated with a large number of benign, precancer and cancer 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 (papillomas) are associated with the low-risk (LR) HPV types, most notably with HPV6 and HPV11. Until recently, the main interest in HPV research 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. With the recent licensing of an effective prophylactic vaccine against the 2 most important LR-HPV types (HPV6 and HPV11), it has become timely to make a systematic survey on the annual disease burden due to these 2 HPV genotypes in our country. These types of data should form the foundation for all calculations of the annual costs needed to treat these diseases by conventional means. Accurate estimates of disease burden are also mandatory for all modelling of the cost-effectiveness of prophylactic HPV6 and HPV11 vaccines. If proven useful for any of these purposes, this document will have fulfilled its purpose. In the first step, published HPV literature was used to create a list of benign, premalignant and malignant lesions associated with this virus at different anatomic sites. GLOBOCAN 2004 (IARC) 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 for obtaining these (y 2005) numbers in Finland. 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 HPV6/11 genotypes in each lesion. Because benign and most of the precancer lesions are not registered by FCR or GLOBOCAN, different approaches had to be used to derive the best estimates for their incidence, based on published literature or other registries (e.g. genital wart registry of the UK and Wales, and mass screening registry of FCR). With a lack of reasonable consensus, a lower and an upper limit was set for the range of estimates. In cases with different age-specific incidence (e.g. genital warts), the population pyramid of Finland was used to calculate the incident cases. Where well established, the different incidence rates among males and females were used to calculate the numbers of incident cases by gender. The malignant neoplasms with established or emerging evidence on the causal role of HPV are listed by their ICD-10 codes in Table I. Included in this list are also 2 controversial malignancies (colorectal cancer and endometrial cancer), of which the contradictory HPV data are critically discussed. The third major cancer in this same category (prostate cancer) was not included in the list, because the data are clearly insufficient to categorize this entity even among the emerging HPV associated malignancies. Estimated disease burden due to HPV6/11 in Finland, calculated as numbers of annual new cases by anatomic region and tumour type is given in Table II, and summarized in Figure 1. The present analysis implicates that a minimum of 12,666 to 13,066 new cases of HPV6- or HPV11-associated clinical lesions would be detected each y in Finland, if all were registered. Notably, these numbers represent the disease burden due to these 2 HPV types. However, these clinical lesions only represent a small minority of the total viral burden due to the infections by these 2 HPV genotypes. This is because the vast majority of all infections by these ubiquitous viruses are latent, being transient in nature and spontaneously resolving within a few months (up to 1 y), without ever developing a clinically detectable disease. This spontaneous clearance does not make these latent infections less important, however, because as long as the virus reservoir exists, it serves as the source of viral transmission to susceptible individuals, with a multitude of HPV6/11 associated pathologies as a potential outcome, as described in this document. The implications of these data in the era of effective prophylactic HPV vaccination against HPV6 and HPV11 should be clear.