Annual cost of hospitalization, inpatient rehabilitation and sick leave of anal cancer in Germany

Abstract

Objective:

Literature on the economic burden of anal cancer in Germany is scarce. About 84% of these cancers are associated with human papillomavirus infection. This study, therefore, aimed to assess the annual costs of human papillomavirus-related anal cancer incurred by hospitalization, inpatient rehabilitation, and sick leave in 2008 in Germany.

Methods:

A cross-sectional retrospective analysis of five German databases covering hospital treatment, inpatient rehabilitation, and sick leave in 2008 was performed. All hospital, inpatient rehabilitation, and sick leave cases due to anal cancer in 2008 were analyzed. Associated numbers of anal cancer hospitalizations, healthcare resource use, and costs were identified and extracted using the ICD-10 code C21 as the main diagnosis. The annual cost of human papillomavirus-related anal cancer was estimated based on the percentage of anal cancer likely to be attributable to human papillomavirus.

Results:

In 2008, there were 5774 hospitalizations (39% males, 61% females), 517 inpatient rehabilitations, and 897 sick leaves due to anal cancer representing costs of €34.11 million. The estimated annual costs associated with human papillomavirus-related anal cancer were €28.72 million, mainly attributed to females (62%). Direct costs accounted for 90% (86% for hospital treatment, 4% for inpatient rehabilitation) and indirect costs due to sick leave accounted for 10% of human papillomavirus-related costs.

Conclusions:

The economic burden of human papillomavirus-related anal cancer in 2008 in Germany is under-estimated, since costs incurred by outpatient management, outpatient chemotherapy, long-term care, premature retirement, and premature death were not included. However, this study is the first analysis to investigate the economic burden of anal cancer in Germany. The estimated annual costs of human papillomavirus-related anal cancer contribute to a significant economic burden in Germany and should be considered when assessing health and economic benefits of human papillomavirus vaccination in both genders.

Keywords::

• Anal cancer
• Human papillomavirus
• Cost of illness
• Germany

Introduction

Anal cancers comprise squamous cell carcinomas of the anal canal and the anal verge, whereas adenocarcinomas in this region are classed as rectal cancer1. The precursor lesion of anal cancer is anal intraepithelial neoplasia (AIN), which is graded from 1 (low-grade) to 3 (carcinoma in situ)2. Although the prevalence of AIN in the general population is unknown, AIN has been detected with increasing frequency, and long-term studies have shown that ∼5% of high-grade AIN lesions progress to invasive cancer2.

Seven regional German cancer registries have reported age-standardized (world) incidence rates of anal cancer of 0.4–1.0 per 100,000 males and 0.6–1.4 per 100,000 females in different parts of the country3. However, to our knowledge, there are no official data on the incidence and prevalence of anal cancer in the German population as a whole. In general, the incidence of anal cancer increases with age and is more common in females than in males4,5.

HPV infection has been detected in 84.2% of anal cancers6. Most HPV-related anal cancers are associated with the high-risk HPV types 16 and 186,7. Several other risk factors for anal cancer have been reported, such as smoking, immunosuppression, receptive anal intercourse, higher lifetime number of sexual partners, and human immunodeficiency virus (HIV) infection7. However, clinical awareness of AIN is less developed than for cervical intraepithelial neoplasia (CIN), the equivalent precursor lesions of cervical cancer, and, as no organized screening for AIN exists, diagnosis is often delayed due to a lack of clinical symptoms⁸.

There are a number of studies assessing the disease burden and cost of HPV-related anal cancer in other countries8–10; however, this is poorly documented in Germany as no studies from the German setting exist. Therefore, the objective of the present study was to estimate the economic burden due to hospitalization, inpatient rehabilitation, and sick leave of HPV-related anal cancer in 2008 in Germany. These data will also be useful in terms of assessing whether an HPV vaccination strategy would be cost-effective, considering the potential vaccine’s impact on the burden of HPV-associated anal cancer in Germany.

Methods

The annual cost of anal cancer was estimated by considering the expenditure of social insurance bodies as proxies for direct medical costs incurred by hospital treatment and inpatient rehabilitation. Indirect costs due to sick leave were estimated using a human capital approach. Outpatient management, patients’ co-payments and out-of-pocket expenses were not considered. Further information on which component is included or not in the study is presented in Table 1.

Table 1.  Cost components of the analysis.

Cost component	Included in the analysis	Not included in the analysis
Direct costs by expenditure of social insurance bodies
Hospitalization^a	X
Expensive chemotherapy during hospitalization^b		X
Outpatient medical services covering physician visits, diagnostics, and treatments		X
Outpatient drugs including chemotherapy		X
Inpatient rehabilitation for employed patients	X
Inpatient rehabilitation for retired patients		X
Outpatient rehabilitation		X
Long-term care^c		X
Indirect costs based on the human capital approach
Sick leave	X
Premature retirement		X
Premature death		X

^aIncluding, inter alia, inexpensive chemotherapy covered and reimbursed by respective diagnosis-related groups.

^bNo expensive chemotherapy that is reimbursed via an additional fee could be linked to the diagnosis-related groups listed in Table 2 due to the nature of the database used (G-DRG Browser)12.

^cVariety of services provided in institutional or home care settings for those who are unable to perform activities of daily living independently for an expected period of at least half a year due to illness or disability.

The study was based on a retrospective cross-sectional analysis of five German databases that cover hospitalizations11, distribution of diagnosis-related groups (DRG) and major categories of treatment during hospital stay12, inpatient rehabilitation13, and sick leave14,15, each with the reference year 2008. Associated numbers of anal cancer hospitalizations, healthcare resource use, and unit costs were identified and extracted using the International Classification of Diseases, 10th revision code for malignant tumor of the anus and anal canal (ICD-10 code C21) as the main diagnosis. The same diagnostic code (C21) could be used for extraction as it is documented in each of the above-mentioned databases11–14 used. Thus, the extracted numbers of cases refer to resource consumption units and not to patients, due to the nature of the databases11–14 used. Annual costs of HPV-related anal cancer were estimated by using the proportion of 84.2% attributable to HPV infection6.

Estimation of direct costs incurred by hospitalization

The annual cost incurred by hospital treatment (medical attendance, care, drugs, devices, physical therapy, board and lodging) of anal cancer (C21 coded as the main diagnosis) was based on the number of hospitalizations and the average cost per hospital stay. The number of hospital stays with the main diagnosis of anal cancer (C21) was extracted from the hospital statistics published by the Federal Statistical Office Germany (Destatis)11. These statistics are by law exhaustive for all Germany11 and provide information on the number of hospitalizations by ICD-10 code, age group, and gender11.

The average hospital treatment cost per C21 hospital stay was derived from the type and number of German diagnosis-related group (G-DRG) positions reimbursed for the main diagnosis of C21. G-DRG data are by law exhaustive for all Germany12. These are published by the Institute for the Hospital Remuneration System (InEK) as G-DRG Browser12, which provides information on type and frequency of reimbursed G-DRGs per ICD-10 main diagnosis as well as type and frequency of major treatment categories such as surgery, radiotherapy, and medical treatment per reimbursed G-DRG position.

Costs for each extracted G-DRG position related to C21 were calculated by multiplying the cost weight of each extracted G-DRG position12 with the Germany-wide average base rate of €2803.05 in 200816,17.

For all G-DRG positions, the G-DRG Browser only lists the top-20 main diagnoses. If a case has a main diagnosis that is among the top-20 of a certain DRG, this case shows up in the Browser data. If a rare main diagnosis uses a G-DRG that is used by many other more frequent main diagnoses, it will not show up in the Browser. Therefore, the extrapolation of costs from the number of cases in the G-DRG Browser to the number of cases from the hospital statistics was supplemented by collection of aggregate anonymized data on the distribution of G-DRG positions for treatment of C21 in one hospital to identify potential important missing G-DRGs.

Hospital treatment costs extrapolated from the G-DRG Browser12 data were stratified by gender assuming the same distribution for costs as for the number of hospitalizations extracted from the hospital statistics11.

Estimation of direct costs incurred by inpatient rehabilitation

For patients with anal cancer, inpatient rehabilitation following acute hospital cancer treatment comprises training to cope with rectal incontinence, nutritional counseling, treatment of radiation damage, etc., and is intended to enable employed patients’ further labor force participation. In Germany, inpatient rehabilitation is paid by the Public Pension Insurance13, whereas acute hospital treatment is paid by sick funds. The annual cost incurred by inpatient rehabilitation due to the main diagnosis of anal cancer (C21) after acute hospital cancer treatment was based on the number and average duration of rehabilitation stays (in days) and the average cost per day.

The number of rehabilitation stays with the main diagnosis of anal cancer (C21) was extracted from rehabilitation statistics published by the holder of the German Public Pension Insurance (DRV)13. These statistics are by law exhaustive for all Germany13 and provide information on the number of inpatient rehabilitation stays and duration in days by ICD-10 3-digit main diagnosis code and gender13. Outpatient rehabilitation is not included in the present study, as the related data are aggregated over disease groups13, thus preventing ICD-10 3-digit codes from being extracted.

The average cost per day of inpatient rehabilitation was also derived from rehabilitation statistics13. Total costs of €2689.84 million13 divided by a total of 24,120,180 days (804,006 stays with a mean of 30 days per stay)13 resulted in an average cost of €111.52 per day for inpatient rehabilitation. The average cost per day is not disease-specific.

The number, duration (in days), and cost of inpatient rehabilitation stays were stratified by gender.

Estimation of indirect costs incurred by sick leave

The annual cost incurred by sick leave due to the main diagnosis anal cancer (C21) was based on the number of sick leaves, the average duration per case in days and cost per day.

The number and duration of sick leaves were estimated in two steps. In the first step, the number of sick leave cases and average duration per sick leave case in days due to the main diagnosis of anal cancer (C21), each by gender, were extracted from statistics covering the population of all compulsory members (i.e., insured without co-insured dependants and pensioners) of the Local Statutory Health Insurance (SHI) fund (AOK), which is the biggest SHI fund in Germany. These statistics are available via the Information System of Federal Health Monitoring (GBE)14. As these data are not exhaustive for all Germany, a second step was applied to extrapolate the numbers and duration of sick leave cases extracted from the AOK statistics14 to the total German compulsory SHI member population based on statistics for the total German SHI population published by the Federal Ministry of Health (BMG), the KM6 statistics15. This was done based on the gender-specific share compulsory AOK members took in the total compulsory SHI member population in 2008 available from the KM6 statistics15.

Using the human capital approach18, overall employee compensation per employee per day was used as cost per day of sick leave. The overall employee compensation per employee per day in 2008 was derived from the Statistical Yearbook19. An overall employee compensation of €1225.84 billion19 divided by 35,845,000 employees19 and 365 days resulted in a cost of €93.69 per employee per day.

The number, duration (in days), and costs incurred by sick leave were stratified by gender.

Estimation of annual cost of anal cancer and of HPV-related anal cancer

The annual cost of anal cancer was estimated by adding costs incurred by hospitalization, inpatient rehabilitation, and sick leave. These annual costs were stratified by direct and indirect costs as well as by gender.

A separate calculation was made to estimate the annual cost of HPV-related anal cancer, based upon the proportion of 84.2% of anal cancers attributable to HPV infection6.

Statistical methods

Due to the nature of the databases11–14 used, which exclusively provide average values of all the cases comprised, no measure of variability could be quoted for the estimated cost figures. This, however, is deemed acceptable as the hospital and rehabilitation statistics11,13 are by law exhaustive for all Germany11,13. In addition, the G-DRG-related base rate16,17 to estimate costs incurred by hospitalization and the cost per day of inpatient rehabilitation13 to estimate costs incurred by inpatient rehabilitation each are Germany-wide averages13,16,17. Hence, the use of Germany-wide averages and the fact that the data are exhaustive allowed us to refrain from sensitivity analysis as no variability is expected. All analyses were performed using Microsoft® Excel 2007 (Microsoft Corp., Redmond, WA).

Results

Direct costs incurred by hospitalization

Number of hospitalizations

In 2008, there were 5774 hospitalizations for anal cancer (C21) in Germany: 2238 for males (39%) and 3536 for females (61%). The number of anal cancer hospital stays increased starting from age 35–39 years and reached a plateau at ∼55–59 years. Sixty per cent of the hospitalizations were for patients older than 60 years; 50% were for patients older than 65 years. In males, the peak hospitalization age range was 65–69 years; for females, there were three distinct peaks in hospitalization age groups (55–59 years, 65–69 years, and >80 years). The distribution of the number of hospitalizations by age group and gender is given in Figure 1.

Figure 1.  Distribution of hospitalizations for anal cancer in 2008 in Germany by age and gender.

Major categories of treatment

The distribution of major treatment categories during hospitalization was derived from the G-DRG codes extracted from the G-DRG Browser12 (Table 2). Most of the hospitalizations due to anal cancer (C21) were linked to radiotherapy exclusively (85%), followed by surgery alone (13%). Combination treatment of surgery and radiotherapy accounted for 1% of the hospitalizations, as did medical treatment (e.g., exploration, chemotherapy) alone. All important G-DRGs for anal cancer treatment seem to be accounted for in the G-DRG Browser as the hospital data showed.

Table 2.  G-DRGs reimbursed for hospital treatment of anal cancer in 2008 in Germany12.

Code	Description	Cost weight	Cost per G-DRG (€)	No. of cases per G-DRG	Major categories of treatment
					S	R	S&R	M
G01Z	Evisceration of the small pelvis	6.937	19,445	10	10
G07C	Appendectomy in the case of peritonitis with extremely severe or severe CC or minor surgery of small and large intestine without extremely severe CC, age >9 years	1.371	3843	1	1
G11B	Pyloromyotomy or anoproctoplastic and reconstruction of the anus and sphincter, age >9 years	0.749	2099	8	8
G15Z	Radiotherapy with major abdominal surgery	4.092	11,470	23			23
G16A	Complex rectal resection with surgery of liver metastases or complicating constellation	7.080	19,846	4	4
G16B	Complex rectal resection without surgery of liver metastases, without complicating constellation	3.757	10,531	243	243
G27A	Radiotherapy of illnesses and disorders of the digestive organs, LoS more than 1 day, more than eight sessions, with extremely severe CC	4.548	12,748	106		106
G27B	Radiotherapy of illnesses and disorders of the digestive organs, LoS more than 1 day, more than eight sessions, without extremely severe CC	2.467	6915	310		310
G29A	Other radiotherapy of illnesses and disorders of the digestive organs, LoS more than 1 day, with extremely severe CC	1.486	4165	112		112
G29B	Other radiotherapy of illnesses and disorders of the digestive organs, LoS more than 1 day, without extremely severe CC	0.972	2725	1176		1176
G60B	Malignant tumors of the digestive organs, LoS 1 day or without extremely severe CC	0.430	1205	25				25
Total				2018	266	1704	23	25

CC, complications or comorbidities; G-DRG, German diagnosis-related group; LoS, length of stay; M, medical; No., number; R, radiotherapy; S, surgery; S&R, surgery and radiotherapy.

Costs

The extracted G-DRGs used to estimate the average cost per hospital case with anal cancer (C21) are listed in Table 2: 2018 cases12 compared to the total of 5774 cases documented in the hospital statistics11. The average cost per hospitalization amounted to €5109 and was applied to the total of 5774 hospitalizations, as the collected hospital data showed that no important G-DRG was missed. Total cost of hospitalization was €29.50 million, with €11.43 million for males (39%) and €18.07 million for females (61%) (Table 3). The main contributors to these costs were radiotherapy (69%) and surgery (28%).

Table 3.  Annual cost (€) of anal cancer incurred by hospitalization, inpatient rehabilitation, and sick leave in 2008 in Germany (inconsistencies are due to rounding).

Cost category	Males	Females	Both genders
Direct costs
Hospitalization	11,434,076	18,065,635	29,499,711
Inpatient rehabilitation	443,731	882,332	1,326,063
Sub-total	11,877,807	18,947,967	30,825,774
Indirect costs
Sick leave	1,152,109	2,127,995	3,280,103
Total	13,029,916	21,075,962	34,105,877

Direct costs incurred by inpatient rehabilitation

In 2008, there were 517 inpatient rehabilitation stays for the main diagnosis of anal cancer (C21) in Germany: 173 for males (33%) and 344 for females (67%). The average duration of stay of 23 days for both genders resulted in a total of 11,891 days of inpatient rehabilitation. Based on an average cost per day of €111.52, the costs incurred by inpatient rehabilitation were estimated at €1.33 million (Table 3).

Indirect costs incurred by sick leave

In 2008, compulsory AOK members comprised 5,409,955 males and 4,067,300 females15. There were 150 sick leave cases due to anal cancer for males, corresponding to a total of 4327 sick leave days (≈28.85 days per case); there were 135 sick leave cases due to anal cancer for females, corresponding to a total of 6517 sick leave days (≈48.27 days per case)14. In 2008, the total German compulsory SHI member population comprised 15,374,034 males and 14,174,791 females15. Hence, the factors were 15,374,034/5,409,955 = 2.8414 for males and 14,174,791/4,067,300 = 3.4851 for females to extrapolate cases and days of sick leave from compulsory AOK members to the German compulsory member population.

There were a total of 897 cases (47% for males, 53% for females) and 35,008 days (35% for males, 65% for females) of sick leave due to the main diagnosis of anal cancer (C21) in 2008 in Germany. At a cost of €93.69 per workday lost, indirect costs incurred by sick leave are estimated at €3.28 million, with €1.15 million attributed to males (35%) and €2.13 million to females (65%) (Table 3).

Annual cost incurred by hospitalization, inpatient rehabilitation, and sick leave

In 2008, the annual cost of anal cancer (C21) amounted to €34.11 million. Of these costs, 90% were direct costs (86% hospitalization, 4% inpatient rehabilitation) and 10% were indirect costs incurred by sick leave (Table 3).

Based on the prevalence of HPV in anal cancer of 84.2%6, the annual cost attributable to HPV infection was estimated at €28.72 million (38% males compared to 62% females).

Discussion

This study estimated that the annual cost due to hospitalization, inpatient rehabilitation, and sick leave incurred by HPV-related anal cancers in Germany was €28.72 million in 2008 (38% males), with 90% direct costs (86% hospitalization, 4% inpatient rehabilitation) and 10% indirect costs due to sick leave.

Several factors contribute to the strength of the present study. Most importantly, the data sources used for the number of cancer-specific hospitalizations11 and inpatient rehabilitations13 were exhaustive for all Germany. These databases were also used in previous cost-of-illness (CoI) analyses20–22.

Limitations of the present study are mainly linked to the cost components covered compared to the components of overall CoI. The present study covered only three out of 10 components of overall CoI (Table 1); it excluded outpatient management, patients’ co-payments and out-of-pocket expenses which are expected to be important contributors to the total economic burden of anal cancer management. In addition to the restrictions mentioned above, costs incurred by complications, side effects, or sequelae of the treatment of anal cancers, such as the need for adult diapers, were not included. It is reported that ∼US$400 million are spent on adult diapers in the US per year8. Given the factors outlined above, it is clear that this study under-estimated the total annual cost of anal cancer and of HPV-related anal cancer in 2008 in Germany to a considerable extent. However, in order to avoid speculative assumptions and to keep a conservative approach, no attempts were made to roughly estimate the potential contribution of all the costs not included.

The present study used a cross-sectional approach to estimate these annual costs. The data used to estimate the number of hospitalizations11, inpatient rehabilitations13, and sick leaves14 are from patients with at least one such resource consumption in the reference year. Hence, as the numbers refer to resource use or consumption units and not to single patients in that year11–14, no patient level information is available with respect to co-morbidities or numbers of hospitalizations, inpatient rehabilitations or sick leaves, each per patient per year. Indeed, in the G-DRG Browser12 data co-morbidity information is exclusively given per reimbursed G-DRG position. As a given G-DRG position applies to inpatient treatment of cases with different underlying main diagnoses, no co-morbidity pattern specific to anal cancer cases (main diagnosis ICD-10 code C21) can be identified and extracted. Additionally, for hospital treatment, no incident cases with high resource consumption can be distinguished from prevalent cases with less resource consumption due to the nature of the databases11,12 available. Thus, the estimated average cost of hospitalization reflects the average cost for all anal cancer cases treated in hospital and is consequently lower than the average cost per patient or per new cases, as patients may be hospitalized several times per year.

In 2008 in Germany, there were 1158 incident cases of anal cancer (403 males and 755 females)23. The 5-year partial prevalence (i.e., number of patients alive with a diagnosis of cancer for no longer than 5 years who are likely to receive primary treatment) is the best suited reference point to be compared with the number of treated cases in 2008 found in the present study. The 5-year partial prevalence amounted to ∼4840 patients with anal cancer in 2008 in Germany, assuming that 2%24 of ∼241,990 patients with colorectal cancer25 suffer from anal cancer. These 5-year partial prevalence data compare well to the 5774 hospitalizations found in the present study for 2008 in Germany.

The estimation of costs incurred by sick leave was based on the gender-specific extrapolation of the AOK data14 to the total German compulsory SHI member population in 200815. This extrapolation may have been limited by the fact that age distribution is not given in the AOK data14 and compulsory AOK members are of somewhat lower socioeconomic status than the average population26. However, in 2008, compulsory AOK members had 11.74 days of sick leave per sick leave case and 106.5 sick leave cases per 100 members27, while the total German compulsory SHI member population had 12.45 days of sick leave per sick leave case and 95.1 sick leave cases per 100 members28. Therefore, the bias introduced by the extrapolation of the cancer-specific sick leave data of the compulsory AOK members14 to the total German compulsory SHI member population15 may be minimal. In addition, the majority (60%) of the hospitalizations for anal cancer were for patients older than 60 years (Figure 1); this is past the average age of retirement of 60.7 years in 2008 in Germany29. Hence, the above-mentioned minimal extrapolation bias only affects a relatively small amount of indirect costs due to sick leave of employed patients with anal cancer, i.e., those younger than the average retirement age.

Due to differences in study designs, national healthcare systems, unit costs, incidence patterns, and in cost components available, the results of the present study are difficult to compare with previous CoI analyses of HPV-related anal cancer8–10. The results of our study, however, are similar to results found for France8 with respect to hospital costs. Costs incurred by hospitalization amounted to €20.33 million (2006 values), with €17.89 million attributable to HPV-infection in France8, compared to €29.50 million and €24.84 million (2008 values), respectively, in our study in Germany.

Conclusion

To our knowledge, this study is the first analysis to investigate the economic burden of anal cancer incurred by hospitalization, inpatient rehabilitation, and sick leave in Germany. The estimated annual costs of HPV-related anal cancer contribute to a significant economic burden of at least €28.72 million in Germany; this information could be useful for decision-makers when considering the potential impact of HPV vaccination on anal cancers in males and females in Germany. Indeed, the quadrivalent HPV vaccine has recently demonstrated high clinical efficacy on anal pre-cancers in males30; this should be considered when assessing the full potential benefits of a HPV vaccination program. Furthermore, these costs are under-estimated since, inter alia, outpatient management and management of precursor lesions could not be included as there is currently no data on this. Hence, further research is required to fully estimate the economic burden of HPV-related anal cancer in Germany.

Transparency

Declaration of funding

This study was funded by Sanofi Pasteur MSD, Lyon, France.

Declaration of financial/other interests

W.H. is an executive physician (Department of General Visceral, Vascular, and Thorax surgery) at the Bogenhausen Hospital, Teaching Hospital of the Technical University of Munich, Munich, Germany, and has received honoraria from Sanofi Pasteur MSD, Lyon, France (SPMSD). P.K.S. and X.C. are employees of IGES Institut GmbH, Berlin, Germany, and have worked on projects of IGES Institut GmbH that have been funded by SPMSD. V.R. is an employee of SPMSD, manufacturer of one HPV vaccine, and L.M. is a former employee of SPMSD. All authors contributed equally to conception and design, acquisition, analysis, and interpretation of the data, as well as to drafting and critical review of the article. All authors have read and approved the final version to be published. JME Peer Reviewers on this manuscript have no relevant financial relationships to disclose.

Acknowledgments

The information contained in this manuscript was presented in part at the 27th International Papillomavirus Conference, Berlin, Germany, September 17–22, 2011; and at the 14th Annual European Congress of the International Society for Pharmacoeconomics and Outcomes Research, Madrid, Spain, November 5–8, 2011.