Olsen et al. BMC Public Health 2012, 12:1082 http://www.biomedcentral.com/1471-2458/12/1082 RESEARCH ARTICLE Open Access Incidence and cost of anal, penile, vaginal and vulvar cancer in Denmark Jens Olsen1*, Tine Rikke Jørgensen2, Kristian Kofoed3 and Helle Kiellberg Larsen3 Abstract Background: Besides being a causative agent for genital warts and cervical cancer, human papillomavirus (HPV) contributes to 40-85% of cases of anal, penile, vaginal and vulvar cancer and precancerous lesions. HPV types 16 & 18 in particular contribute to 74-93% of these cases. Overall the number of new cases of these four cancers may be relatively high implying notable health care cost to society. The aim of this study was to estimate the incidence and the health care sector costs of anal, penile, vaginal and vulvar cancer. Methods: New anogenital cancer patients were identified from the Danish National Cancer Register using ICD-10 diagnosis codes. Resource use in the health care sector was estimated for the year prior to diagnosis, and for the first, second and third years after diagnosis. Hospital resource use was defined in terms of registered hospital contacts, using DRG (Diagnosis Related Groups) and DAGS (Danish Outpatient Groups System) charges as cost estimates for inpatient and outpatient contacts, respectively. Health care consumption by cancer patients diagnosed in 2004–2007 was compared with that by an age- and sex-matched cohort without cancer. Hospital costs attributable to four anogenital cancers were estimated using regression analysis. Results: The annual incidence of anal cancer in Denmark is 1.9 per 100,000 persons. The corresponding incidence rates for penile, vaginal and vulvar cancer are 1.7, 0.9 and 3.6 per 100,000 males/females, respectively. The total number of new cases of these four cancers in Denmark is about 270 per year. In comparison, the total number of new cases cervical cancer is around 390 per year. The total cost of anogenital cancer to the hospital sector was estimated to be 7.6 million Euros per year. Costs associated with anal and vulvar cancer constituted the majority of the costs. Conclusions: Anogenital cancer incurs considerable costs to the Danish hospital sector. It is expected that the current HPV vaccination program will markedly reduce this burden. Keywords: Anogenital, Cancer, Cost, Incidence, HPV Background protection against infection, persistent infection and low The introduction of two vaccines against human papillo- and high grade lesions in male and female populations, mavirus (HPV) types 16 & 18 and types 6, 11, 16 & 18, respectively [7-9]. respectively, was primarily intended to protect against Cervical cancer is the second most common cancer cervical cancer (and precancerous lesions) and genital among women worldwide and is the fifth most frequent warts. However, HPV also contributes to 40-85% of all cancer among Danish women [10-12]. Less information cases of anal, penile, vaginal and vulvar cancer and pre- is available on other HPV-related cancers but the total cancerous lesions. HPV types 16 & 18 in particular con- number of new cases of anal, penile, vaginal and vulvar tribute to 74-93% of these cases [1-6] and clinical cancer may be relatively high, implying considerable studies of the quadrivalent HPV vaccine has proven health care costs to society [11]. Although the incidence of cervical cancer has remained stable over the last dec- * Correspondence: [email protected] ade [11,13], the incidence of anal and vulvar cancer has 1Centre for Applied Health Services Research and Technology Assessment increased [11]. (CAST), University of Southern Denmark, J. B. Winslows Vej 9B, 5000 The aim of this study was to estimate the incidence and Odense C, Denmark Full list of author information is available at the end of the article the health care sector cost of anal, penile, vaginal and © 2012 Olsen et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Olsen et al. BMC Public Health 2012, 12:1082 Page 2 of 7 http://www.biomedcentral.com/1471-2458/12/1082 vulvar cancer managed at the hospital level. The results generalized linear regression model (GLM), applying a will contribute to a forthcoming cost-effectiveness ana- log link function and assuming an inverse Gaussian lysis of HPV vaccination that, besides cervical cancer and distribution. Finally, the estimated health care costs genital warts, will include the vaccine’s protection against were derived by multiplying the predictions from the anal, penile, vaginal and vulvar cancer. two components (part 1 and 2) together. When the data for this study was obtained, data on Methods cancer incidence (the Danish National Cancer Register) Patient data were extracted from Danish national regis- was only available up until 2007, while data on DRG ters, which are linked through individuals’ unique regis- and DAGS charges in the National Patient Register tration number (CPR-number). The Danish health were only available from 2006 (given that the same, service has a long tradition of recording health service and relatively novel, version of the DRG- and DAGS- use and each contact with primary health care (e.g. gen- charges should be applied for all years). Therefore, we eral practitioner, public and private specialist, dentist, used a combined cross-sectional and longitudinal ap- physiotherapist) and secondary health care (e.g. hospital proach for the data analysis, where patients diagnosed admission, outpatient visits) is recorded with related during 2004–2007 had an associated resource use for data on age, sex, type of contact, speciality, fee/charge, 2006–2008. This allowed us to estimate the costs 0– diagnoses (secondary health care only) and procedure 12 months before the date of diagnosis (e.g. 2006 re- code. The present study was approved by the Danish source use data for a patient diagnosed in 2007) and Data Protection Agency (J. No. 2010-41-4305). the costs 0–12 months, 13–24 months (e.g. 2008 re- The analysis was conducted from a hospital sector per- source use data for a patient diagnosed in 2006) and spective, as the relevant cancer types are almost exclu- 25–36 months after the date of diagnosis (e.g. 2008 re- sively diagnosed and treated at hospitals. New cancer source use data for a patient diagnosed in 2005). patients were identified via specific ICD-10 diagnosis Results are thus presented as yearly cost estimates for codes in the Danish National Cancer Register. Their an- the year before, the 1st year, the 2nd year and the 3rd nual hospital resource use was estimated based on hos- year after the date of diagnosis for patients alive at the pital contacts recorded in the National Patient Register, respective times. We included costs for the year before which defines resource use by the DRG (Diagnosis diagnosis so that we could estimate the costs of initial Related Groups) system for admissions and by the Da- examinations and diagnostics. Given the perspective of nish outpatient charges (DAGS charges) for outpatient this analysis, the hospital cost estimates include medi- visits (including emergency unit contacts) [14]. The 2008 cation related to hospital contacts, radiotherapy, DRG and DAGS charges were used as cost estimates. chemotherapy and specialized rehabilitation. The cohort of cancer patients was defined as patients Costs are presented in Euros. Future costs (i.e. cost registered in the Danish National Cancer Register during estimates for the 2nd and 3rd years after diagnosis) were 2004–2007 with anal, penile, vaginal or vulvar cancer as discounted using a 3% annual discount rate to represent the primary localization. The patients were identified their present value. When estimating the total average using the ICD-10 codes: C21 (anal cancer), C60 (penile health care cost per patient, we adjusted for deaths dur- cancer), C52 (vaginal cancer) and C51 (vulvar cancer). ing the observation period. For the cohort of cancer patients diagnosed during The number of diagnosed precancerous lesions was 2004–2007, health care use in 2006–2008 was com- estimated based on data from the National Pathology pared with an age- and sex-matched cohort without Register. It was not possible to estimate treatment costs cancer (controls). Five controls were identified for each for these lesions (some of which progress to anogenital cancer patient. The hospital costs associated with the cancer) separately, however, as many of these cases are controls were subtracted from the costs associated with diagnosed and treated by privately practising specialists the cancer patients (to identify the extra costs related to in the primary care sector. As diagnoses are not system- cancer), but this was done in regression analyses in atically registered for the primary care sector, it was im- which costs attributable to anal, penile, vaginal and vul- possible to distinguish contacts related to precancerous var cancer were estimated with cancer (yes/no) as an lesions from other contacts. explanatory dummy variable. As a substantial number Data were analysed using SAS software version 9.2 of the control patients incurred no health care costs (SAS Institute Inc., Cary, NC, USA). (i.e. cost = 0), a two-part model was applied [15-17]. In this analysis, the probability that the patient had zero Results or non-zero costs was first predicted via logistic re- The incidence of the four anogenital cancers is shown in gression analysis. Secondly, the level of cost condi- Table 1. In females, the incidence is highest for vulvar tional on having positive costs was predicted using a cancer and then anal cancer, and in males the incidence Olsen et al. BMC Public Health 2012, 12:1082 Page 3 of 7 http://www.biomedcentral.com/1471-2458/12/1082 Table 1 Incidence of anal, penile, vaginal and vulvar cancer and precancerous lesions Gender Year No.