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Int J STD AIDS OnlineFirst, published on February 12, 2015 as doi:10.1177/0956462415573121
Original research article
The costs of managing genital warts in the UK by devolved nation: England, Scotland, Wales and Northern Ireland
International Journal of STD & AIDS 0(0) 1–7 ! The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0956462415573121 std.sagepub.com
VAH Coles1, R Chapman2, T Lanitis2 and SM Carroll1
Abstract Genital warts, 90% of which are caused by human papilloma virus types 6 and 11, are a significant problem in the UK. The cost of managing genital warts was previously estimated at £52.4 million for 2010. The objective of this study was to estimate the cost of genital warts management up to 2012 in the UK and by jurisdiction. Population statistics and the number of reported genital warts cases in genito-urinary medicine clinics were obtained and extrapolated to 2012. Cases of genital warts treated in primary care were estimated from The Health Improvement Network database. The number of visits and therapy required were estimated by genito-urinary medicine experts. Costs were obtained from the appropriate national tariffs. The model estimated there were 220,875 genital warts cases in the UK in 2012, costing £58.44 million (£265/patient). It estimated 157,793 cases in England costing £41.74 million; 7468 cases in Scotland costing £1.90 million; 7095 cases in Wales costing £1.87 million; and 3621 cases in Northern Ireland costing £948,000. The full National Health Service costs for the management of genital warts have never previously been estimated separately for each jurisdiction. Findings reveal a significant economic burden, which is important to quantify when understanding the value of quadrivalent human papilloma virus vaccination.
Keywords Genital warts, human papilloma virus, treatment, vaccination, prevention Date received: 17 October 2014; accepted: 18 January 2015
Introduction Genital warts (GW) are the second most commonly diagnosed sexually transmitted infection (STI) in genitourinary medicine (GUM) clinics in England,1,2 with more than 136,000 GW diagnoses made in England in 2013, over 73,000 of which were new cases and nearly 63,000 of which were recurrent or persistent.1 Diagnoses of GW in England and Wales have been increasing since 2000,2 and Public Health England (PHE) estimate an 8% increase in GW incidence rates in England between 2003 and 2012.3 GW are caused by human papilloma virus (HPV), with subtypes 6 and 11 responsible for 90% of cases.4 Since September 2012, a quadrivalent HPV vaccine protecting against infection with HPV 6 and 11 has been offered to all 12- to 13-year-old girls throughout the UK. However, any impact of the national immunisation programme upon GW incidence will not be seen until the recipients reach sexual debut, which was recently estimated to be a median age of 16 for those aged 16–24 in the UK.5
There are a number of published estimates of the cost of GW in the United Kingdom2,6–10 although some of these are rather dated,6,7 some use small sample sizes,7,8,10 most focus exclusively on cases and costs in GUM clinics,6–8,10 and some focus solely on England or England and Wales.2,7 The most recent study estimated the UK cost of managing GW in 2010 as £52.4 million, using secondary GUM clinic data from the Health Protection Agency (HPA) and primary care data from the Health Improvement Network (THIN) database.9 The present study sought to update the analysis, estimating the UK cost of managing GW in 2012, and to calculate the cost for each of
1 2
Sanofi Pasteur MSD, Maidenhead, UK Evidera, London, UK
Corresponding author: Victoria AH Coles, Sanofi Pasteur MSD, Mallards Reach, Bridge Avenue, Maidenhead, Berkshire, SL6 1QP, UK. Email: [email protected].
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the UK’s four nations (England, Scotland, Wales, and Northern Ireland (NI)).
Methods A previously published economic model9 was updated to estimate the costs of GW management in 2012 across the UK’s four nations. The model structure is illustrated in supplementary Figure 1. The model segregated patients treated in GUM clinics and those seen in primary care. Patients treated in GUM clinics were divided into those with first episodes of GW, persistent and recurrent cases. Persistent episodes are defined as those persisting for longer than, or recurring within, 3 months, whilst recurrent cases are defined as a re-appearance of GW after more than 3 months. Each of these groups was further sub-divided into normal and difficult-totreat patients, the latter of which include human immunodeficiency virus (HIV)-positive patients with poorly-controlled disease, immunosuppressed, elderly, diabetic, and pregnant patients. Difficult-to-treat patients tend to have a higher number of visits than normal patients and have surgery as a treatment option in the model.
Patients considered normal in terms of their treatment were further divided into those with keratinised warts (firm, usually occurring on dry, hairy skin) and non-keratinised warts (soft and usually occurring on warm, moist, non-hair bearing skin). Patients with either classification of warts were split according to the treatments received, consisting of topical treatment (imiquimod or podophyllotoxin), destructive treatment (cryotherapy), or a combination. The number of GW cases accessing primary care was based on estimates of the total population, using population data from the Office of National Statistics (ONS, 2002–2010) for England and Wales,11 the General Register Office for Scotland (2002–2010),12 the Northern Ireland Statistics and Research Agency (2002–2011),13 and 2011 census data for England, Wales and Scotland.14 Population estimates for 2012 were calculated by fitting a linear trend on the available population data by jurisdiction. Rates for presentation of GW in primary care, the number of visits, and the rates of receipt of topical or destructive therapy were estimated using 2008–09 data from the THIN database.15 These rates were applied to the 2012 population estimates for each jurisdiction. The total number of GP visits for men and for women was
Figure 1. Proportion of (a) GW cases and (b) associated management costs in the UK and for each jurisdiction, by location of treatment and episode classification. Labels on each segment indicate the absolute case numbers (a) and costs in thousands (b).
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varied by 10% in sensitivity analyses. Patients presenting with GW in primary care, but not treated, were assumed to have been treated in GUM clinics. The number of GW cases treated in GUM clinics was based on KC60 diagnostic statistics. Data were obtained from the HPA for the UK and England;16 the Information Services Division for Scotland;17 the Communicable Disease Surveillance Centre for Wales;18 and the Public Health Agency for NI.19 At the time of the analysis, data were only available up to 2011 for England; 2009 for Scotland; 2010 for Wales and NI; and 2009 for the UK collectively. Data for the UK and each jurisdiction were extrapolated using polynomial regression equations to estimate the number of annual cases between 2000 and 2012. In the absence of long-term data for Wales, where only 5 years’ data were available, a regression equation could not be obtained so a linear fit was used. This approach was used to estimate the number of patients with first attack, persistent and recurrent GW cases. Where persistent and recurrent cases were grouped together separate estimates were derived by assuming the same distribution of persistent and recurrent cases as were observed in the UK as a whole.
A questionnaire, developed with two clinicians, was administered to four expert GUM consultants to estimate the number of visits and treatments based on the type of case, gender and type of wart (keratinised or non-keratinised), and for the patients classified as difficult-to-treat, which were all assumed to incur costs of a surgical procedure. The estimated mean number of visits was between 2.18 and 2.50 for non-complicated cases, depending on the episode type and therapy, and 10 for difficult-to-treat cases. These were used in base case analyses, and the upper and lower bounds of the range of clinicians’ estimates were used in sensitivity analyses as previously published.9 Unit costs (Table 1) were taken from NHS Payment by Results (PbR) reference cost schedules,20 the Personal Social Services Research Unit (PSSRU),21 and the British National Formulary (BNF).22 Topical treatment and cryotherapy costs were assumed to be included in the GUM clinic visit cost based on information from a GUM accounting authority. Podophyllotoxin is available as a cream as well as a solution, and in the case of podophyllotoxin use in primary care, the model assumed the same cost and
Table 1. Unit costs used to estimate the cost of managing genital warts (GW) in the UK. Cost items
Code
Unit cost (£)
Source
GUM Adult first attendance – single professional (WF01B)
360 (treatment function code)
133.00
Adult follow-up attendance – single professional (WF01A)
360 (treatment function code)
82.00
GP visit costs
10.8 b (Table number)
43.00
Outpatient attendance tariff, PbR arrangements for 2012–2013, Department of Health, 5 April 2013, Sheet: ‘‘2. OP Attendances’’.20 Outpatient attendance tariff, PbR arrangements for 2012–2013, Department of Health, 5 April 2013, Sheet: ‘‘2. OP Attendances’’.20 GP (with qualification) unit cost per surgery consultation lasting 11.7 minutes, including direct care staff costs. PSSRU (2012) p183.21
MA04B (HRG code)
1370.00
Outpatient attendance tariff, PbR arrangements for 2012–2013, Department of Health, 5 April 2013, Sheet: ‘‘01. APC & OPROC’’.20
–
48.39
–
12.38
12 sachet pack, BNF 65, BMJ Group and Pharmaceutical Press (2013).22 0.5% in alcoholic basis, 3 mL (with applicators), BNF 65, BMJ Group and Pharmaceutical Press (2013).22
Surgery costs Lower genital tract intermediate procedures without CC Drug costs Imiquimod (Aldara) Podophyllotoxin (Warticon solution)
CC: complications and comorbidities; PbR: payment by results; GP: general practitioner; GUM: genitourinary medicine; OP: outpatient; PSSRU: Personal Social Services Research Unit; BNF: British National Formulary; APC: admitted patient care; OPROC: outpatient procedure.
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Sensitivity analyses
Figure 2. Proportion of GW management costs incurred for men and women in the UK and for each jurisdiction. Labels on each segment indicate the absolute costs in thousands.
efficacy. For sensitivity analyses, unit costs were varied by 20%.
Results The model predicts that 220,875 people in the UK were treated for GW in 2012. Of these, 203,883 were treated in GUM clinics (including 33,134 referred from primary care) and 16,992 were treated in primary care. Of those treated in GUM clinics, 103,537 (50.8%) were first episodes, 69,707 (34.2%) were recurrent, and 30,639 (15.0%) were persistent cases (Figure 1a); 2071 patients treated for a first episode of GW in GUM clinics were classified as difficult-to-treat according to our criteria. The total UK management cost in 2012 was £58.44 million; £55.55 million for patients in GUM clinics and £2.89 million for patients in primary care (Figure 1b). In all, 56.2% of costs (£32.85 million) were associated with the treatment of GW in men (Figure 2). The average cost per patient was £265. These updated estimates represent an increase of 31,016 cases (16.3%) and £6.06 million (11.6%) on the 2010 estimate.9 Analysis by country estimated that 157,793, 7468, 7095, and 3621 people were treated for GW in England, Scotland, Wales, and NI, respectively, in 2012, with first episodes accounting for the largest proportion of cases and costs in each jurisdiction (Figure 1). Between 9.0% (in England) and 19.1% (in Scotland) of patients were treated in primary care. The total management cost in 2012 was estimated to be £41.74 million, £1.90 million, £1.87 million, and approximately £948,000 in England, Scotland, Wales, and NI, respectively. In all jurisdictions, men accounted for a greater proportion of costs than women (51.4%– 57.6%; Figure 2). The average cost per patient across
One-way sensitivity analyses were conducted to explore the impact of clinicians’ estimates (Figure 3a) and the unit costs used in the analysis (Figure 3b). Of the parameters tested, the cost of GW management in the UK was most sensitive to the proportion of patients which are deemed difficult to treat. In the base case, it was assumed that 2% of patients were difficult to treat. Using the upper bound of the range of clinicians’ estimates (8%) led to a 41.9% increase in total costs to £82.9 million, while the lower bound (0.05%) led to a 13.6% decrease. The next most important parameter was the maximum number of visits for normally treated warts. The model assumed that patients would make a maximum of five visits in the base case. Decreasing this to three visits led to an 8.2% decrease in costs, whilst increasing it to eight led to a 12.3% increase in costs. In terms of unit costs, the UK GW management cost was most sensitive to the cost of follow-up appointments. Varying this by 20% led to a 9.2% change in the total cost of GW management.
Discussion In its framework for sexual health improvement, the UK Department of Health (DH) has emphasised the importance of good individual sexual health as a key public health priority.23 GW are one of the most common STIs in the UK, with a significant epidemiological burden, particularly in those in their teens and early twenties.1 In the current analysis, the total UK cost of managing GW in 2012 was estimated at £58.44 million, 95% of which was incurred in GUM clinics. This is an update to a previous estimate of £52.4 million for 20109 and exceeds figures reported in earlier studies.2,6–8 These differences are primarily due to the inclusion of primary care costs, robust estimates of unit costs through PbR data, and the use of the most up-to-date surveillance data in the present analysis. This study estimated the full and up-to-date costs of GW management by UK jurisdiction, and, to our knowledge, is the first to do so. The analysis suggests that the financial implications of GW are substantial in all four jurisdictions, with management costs of £41.74 million in England, £1.90 million in Scotland, £1.87 million in Wales, and £948,000 in NI. These findings are validated by PHE STI data published since the construction of this model, which report 73,893 new GW diagnoses (first episodes) in GUM clinics in England in 2012,3 suggesting that our model overestimated the burden by just 7%.
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Figure 3. Tornado diagram illustrating results of sensitivity analyses for GW management costs in the UK in 2012. (a) Clinicians’ estimates were varied across the range of estimates obtained, and the total number of GP visits made by women and by men were each varied by þ/10%. (b) Costs obtained from PbR reference cost schedules, the PSSRU and the BNF were varied by þ/20%. Example interpretation (top line of (a), proportion of patients difficult to treat): using the upper bound of the range of clinicians’ estimates (8%) led to an increase in total costs to £82.9 million, while the lower bound (0.05%) led to a decrease in total costs to £50.5 million.
The DH has stated the need to ‘‘continue to work to reduce the rate of STIs using evidence-based preventative interventions and treatment initiatives’’.23 In addition to public health benefits, the current analysis suggests that prevention of GW could yield significant savings for the NHS. The quadrivalent HPV vaccine, which has been offered to all 12- to 13-year-old girls in the UK since September 2012, may be associated with a decline in GW cases in the coming years as these adolescents reach sexual debut. The impact of GW upon the health and well-being of patients has been demonstrated in recent studies suggesting that GW are associated with a reduction in quality of life, which may be most pronounced in adolescent girls.24,25 This demographic group is likely to
benefit most directly from the current HPV vaccination programme. Both the financial and quality of life burdens of GW should be recognised and appropriately quantified in order to understand the full value of quadrivalent HPV vaccination. The vaccine is not currently offered to boys as the majority are thought to be protected through herd immunity although current real-world evidence is inconclusive. The first published data demonstrated that in Australia a high-coverage girls’ immunisation programme was associated with a decline in GW in boys.26 However, more recent data from Denmark demonstrate that although the vaccination programme was successful, such indirect effects on boys were not seen.27 This is thought to be due to much higher rates of
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international travel in Europe than in a large, relatively isolated country such as Australia, particularly in adolescent and early adult years, when STI rates tend to be highest. In this sense, the UK is likely to be much more similar to Denmark and therefore the effect of herd immunity for the protection of boys is, in reality, likely to be limited.28 Additionally, such indirect effects are not, by definition, conferred to other high-risk groups such as men who have sex with men. Universal adolescent vaccination has already been introduced in a number of countries, including the USA,29 Canada,30 Australia,10 Austria,31 and the Saxony region of Germany.32 Extending HPV vaccination to boys may have an additive effect, further reducing the burden of GW. This is especially pertinent given that both the PHE surveillance data1,3 and the present analysis suggest that the burden of GW is higher in men. Our analysis is subject to a number of limitations. Firstly, estimates of treatment patterns were based on the opinions of four clinical experts. Further, there was some variability in their estimates, and the results of the analysis were shown to be sensitive to this uncertainty. Secondly, it was assumed that the treatment given, the unit costs of treatment, and the proportion of GW cases classified as difficult-to-treat were the same across jurisdictions. Thirdly, the number of GW cases estimated for the UK does not match the sum of GW cases in England, Wales, Scotland, and NI in some years. This is because the number of GW cases was extrapolated independently for each jurisdiction and for the UK, which led to differences in predicted trends across jurisdictions. Future research should focus on addressing these limitations, such as using administrative data to investigate the differences between treatment patterns in each jurisdiction. Nevertheless, our analysis suggests that the high epidemiological burden of GW in the UK is associated with significant costs in all four constituent nations. Continued routine use of the quadrivalent HPV vaccine, as well as extension of the programme to adolescent boys, may reduce this financial burden, and would align with the UK Government’s priorities around prevention. Declaration of Conflicting Interests The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: VC and SC are employees of Sanofi Pasteur MSD, which holds a marketing authorisation for one of the HPV vaccinations in use in the UK. RC and TL have received consultancy fees from Sanofi Pasteur MSD.
Funding The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded in full by Sanofi Pasteur MSD.
References 1. Public Health England. Sexually transmitted infections and chlamydia screening in England, 2013, http:// www.hpa.org.uk/hpr/archives/2014/hpr2414_AA_stis. pdf (2014, accessed 30 June 2014). 2. Desai S, Wetten S, Woodhall SC, et al. Genital warts and cost of care in England. Sex Transm Infect 2011; 87: 464–468. 3. Public Health England. Sexually transmitted infections and chlamydia screening in England, 2012, http:// www.hpa.org.uk/hpr/archives/2013/hpr2313.pdf (2013, accessed 30 June 2014). 4. Von Krogh G. Management of anogenital warts (condylomata acuminata). Eur J Dermatol 2001; 11: 598–603. 5. Mercer CH, Tanton C, Prah P, et al. Changes in sexual attitudes and lifestyles in Britain through the life course and over time: findings from the National Surveys of Sexual Attitudes and Lifestyles (Natsal). Lancet 2013; 382: 1781–1794. 6. Brown RE, Breugelmans JG, Theodoratou D, et al. Costs of detection and treatment of cervical cancer, cervical dysplasia and genital warts in the UK. Curr Med Res Opin 2006; 22: 663–670. 7. Langley PC, White DJ and Drake SM. The costs of treating external genital warts in England and Wales: a treatment pattern analysis. Int J STD AIDS 2004; 15: 501–508. 8. Woodhall SC, Jit M, Cai C, et al. Cost of treatment and QALYs lost due to genital warts: data for the economic evaluation of HPV vaccines in the United Kingdom. Sex Transm Dis 2009; 36: 515–521. 9. Lanitis T, Carroll S, O’Mahony C, et al. The cost of managing genital warts in the UK. Int J STD AIDS 2012; 23: 189–194. 10. Pharmaceutical Benefits Advisory Committee (PBAC). November 2011 PBAC meeting outcomes – Positive recommendations, http://www.pbs.gov.au/industry/listing/ elements/pbac-meetings/pbac-outcomes/2011-11/nov2011-pbac-outcomes-positive-recommendations.pdf (2011, accessed 1 July 2014). 11. Office for National Statistics. Population Estimates for England and Wales, Mid-2002 to Mid-2010 Revised (Subnational), http://www.ons.gov.uk/ons/rel/ pop-estimate/population-estimates-for-england-andwales/mid-2002-to-mid-2010-revised–subnational-/ index.html (2013, accessed 30 June 2014). 12. General Register Office for Scotland. Unrevised Mid-Year Population Estimates based on the 2001 Census, http://www.gro-scotland.gov.uk/statistics/theme /population/estimates/mid-year/archive/index.html (2003-2012, accessed 30 June 2014). 13. Northern Ireland Statistics and Research Agency. MidYear Population Estimates, http://www.nisra.gov.uk/ demography/default.asp17.htm (2003-2012, last accessed 30 June 2014). 14. Office for National Statistics. 2011 Census, Population and Household Estimates for the United Kingdom, http:// www.ons.gov.uk/ons/rel/census/2011-census/populationand-household-estimates-for-the-united-kingdom/ index.html (2012, accessed 30 June 2014).
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15. CSD Medical Research UK. The Health Improvement Network (THIN) data, http://csdmruk.cegedim.com/ our-data/our-data.shtml (data on file). 16. Health Protection Agency. Sexually Transmitted Infections Annual Data, http://www.hpa.org.uk/web/ HPAweb&HPAwebStandard/HPAweb_C/120334802 6613 (2012, accessed 28 February 2013). 17. Information services division (ISD), NHS Scotland. STI (GUM) data, http://www.isdscotlandarchive.scot.nhs.uk/ isd/4907.html (2010, accessed 7 June 2013). 18. Public Health Wales Communicable Disease Surveillance Centre. HIV and STI trends in Wales, Surveillance Report, www.wales.nhs.uk/sites3/docopen.cfm?orgid¼ 457&id¼190822 (2012, accessed 7 June 2013). 19. Public Health Agency. HIV and STI surveillance in Northern Ireland 2011: an analysis of data for the calendar year 2010, http://www.publichealth.hscni.net/ publications/hiv-and-sti-surveillance-northern-ireland2011-analysis-data-calendar-year-2010 (2011, accessed 7 June 2013). 20. Department of Health. Payment by Results in the NHS: tariff for 2012 to 2013, https://www.gov.uk/government/ publications/confirmation-of-payment-by-results-pbrarrangements-for-2012-13 (2013, accessed 7 June 2013). 21. Curtis L. Unit Costs of health and social care 2012, Personal Social Services Research Unit (PSSRU), http://www.pssru.ac.uk/archive/pdf/uc/uc2012/full-withcovers.pdf (2012, accessed 7 June 2013). 22. Royal Pharmaceutical Society of Great Britain. British National Formulary (BNF) 65, http://www.bnf.org/bnf/ index.htm (2013, accessed 7 June 2013). 23. Department of Health. A Framework for Sexual Health Improvement in England, https://www.gov.uk/ government/uploads/system/uploads/attachment_data/ file/142592/9287-2900714-TSO-SexualHealthPolicyNW_ ACCESSIBLE.pdf (2013, accessed 1 July 2014). 24. Woodhall SC, Jit M, Soldan K, et al. The impact of genital warts: loss of quality of life and cost of treatment in
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eight sexual health clinics in the UK. Sex Transm Infect 2011; 87: 458–463. Vriend HJ, Nieuwkerk PT and van der Sande MAB. Impact of genital warts on emotional and sexual wellbeing differs by gender. Int J STD AIDS 2014; 25: 949–955. Ali H, Donovan B, Wand H, et al. Genital warts in young Australians five years into national human papillomavirus vaccination programme: national surveillance data. BMJ 2013; 346: f2032. Baandrup L, Blomberg M, Dehlendorff C, et al. Significant decrease in the incidence of genital warts in young Danish women after implementation of a national Human Papillomavirus vaccination program. Sex Transm Dis 2013; 40: 130–135. Stanley M, O’Mahony C and Barton S. HPV Vaccination – what about the boys. BMJ 2014; 349: G4783. Centers for Disease Control and Prevention (CDC). Morbidity and Mortality Weekly Report (MMWR), http://www.cdc.gov/mmwr/pdf/wk/mm6050.pdf (2011, accessed 1 July 2014). National Advisory Committee on Immunization (NACI). Canada communicable disease report, http://www.phacaspc.gc.ca/publicat/ccdr-rmtc/12vol38/acs-dcc-1/assets/ pdf/12vol-38-acs-dcc-1-eng.pdf (2012, accessed 1 July 2014). Bundesministerium Fu¨r Gesundheit. Newsletter Kinder – und Jugendgesundheit Ausgabe 4/2013, http://www. bmg.gv.at/cms/home/attachments/1/7/6/CH1418/CMS 1378112443973/erweiterung_des_kinderimpfprogramms_ um_hpv_impfung_4_2013.pdf (2013, accessed 1 July 2014). Gesellschaft fu¨r Hygiene, Umweltmedizin und Schutzimpfungen in Sachsen e.V. (GHUSS). Empfehlungen der Sa¨chsischen Impfkommission zur Durchfu¨hrung von Schutzimpfungen im Freistaat Sachsen, http://www.gesunde.sachsen.de/download/lua/ LUA_HM_Impfempfehlungen_E1.pdf (2014, accessed 1 July 2014).
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Int J STD AIDS OnlineFirst, published on February 12, 2015 as doi:10.1177/0956462415573121
Original research article
The costs of managing genital warts in the UK by devolved nation: England, Scotland, Wales and Northern Ireland
International Journal of STD & AIDS 0(0) 1–7 ! The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0956462415573121 std.sagepub.com
VAH Coles1, R Chapman2, T Lanitis2 and SM Carroll1
Abstract Genital warts, 90% of which are caused by human papilloma virus types 6 and 11, are a significant problem in the UK. The cost of managing genital warts was previously estimated at £52.4 million for 2010. The objective of this study was to estimate the cost of genital warts management up to 2012 in the UK and by jurisdiction. Population statistics and the number of reported genital warts cases in genito-urinary medicine clinics were obtained and extrapolated to 2012. Cases of genital warts treated in primary care were estimated from The Health Improvement Network database. The number of visits and therapy required were estimated by genito-urinary medicine experts. Costs were obtained from the appropriate national tariffs. The model estimated there were 220,875 genital warts cases in the UK in 2012, costing £58.44 million (£265/patient). It estimated 157,793 cases in England costing £41.74 million; 7468 cases in Scotland costing £1.90 million; 7095 cases in Wales costing £1.87 million; and 3621 cases in Northern Ireland costing £948,000. The full National Health Service costs for the management of genital warts have never previously been estimated separately for each jurisdiction. Findings reveal a significant economic burden, which is important to quantify when understanding the value of quadrivalent human papilloma virus vaccination.
Keywords Genital warts, human papilloma virus, treatment, vaccination, prevention Date received: 17 October 2014; accepted: 18 January 2015
Introduction Genital warts (GW) are the second most commonly diagnosed sexually transmitted infection (STI) in genitourinary medicine (GUM) clinics in England,1,2 with more than 136,000 GW diagnoses made in England in 2013, over 73,000 of which were new cases and nearly 63,000 of which were recurrent or persistent.1 Diagnoses of GW in England and Wales have been increasing since 2000,2 and Public Health England (PHE) estimate an 8% increase in GW incidence rates in England between 2003 and 2012.3 GW are caused by human papilloma virus (HPV), with subtypes 6 and 11 responsible for 90% of cases.4 Since September 2012, a quadrivalent HPV vaccine protecting against infection with HPV 6 and 11 has been offered to all 12- to 13-year-old girls throughout the UK. However, any impact of the national immunisation programme upon GW incidence will not be seen until the recipients reach sexual debut, which was recently estimated to be a median age of 16 for those aged 16–24 in the UK.5
There are a number of published estimates of the cost of GW in the United Kingdom2,6–10 although some of these are rather dated,6,7 some use small sample sizes,7,8,10 most focus exclusively on cases and costs in GUM clinics,6–8,10 and some focus solely on England or England and Wales.2,7 The most recent study estimated the UK cost of managing GW in 2010 as £52.4 million, using secondary GUM clinic data from the Health Protection Agency (HPA) and primary care data from the Health Improvement Network (THIN) database.9 The present study sought to update the analysis, estimating the UK cost of managing GW in 2012, and to calculate the cost for each of
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Sanofi Pasteur MSD, Maidenhead, UK Evidera, London, UK
Corresponding author: Victoria AH Coles, Sanofi Pasteur MSD, Mallards Reach, Bridge Avenue, Maidenhead, Berkshire, SL6 1QP, UK. Email: [email protected].
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the UK’s four nations (England, Scotland, Wales, and Northern Ireland (NI)).
Methods A previously published economic model9 was updated to estimate the costs of GW management in 2012 across the UK’s four nations. The model structure is illustrated in supplementary Figure 1. The model segregated patients treated in GUM clinics and those seen in primary care. Patients treated in GUM clinics were divided into those with first episodes of GW, persistent and recurrent cases. Persistent episodes are defined as those persisting for longer than, or recurring within, 3 months, whilst recurrent cases are defined as a re-appearance of GW after more than 3 months. Each of these groups was further sub-divided into normal and difficult-totreat patients, the latter of which include human immunodeficiency virus (HIV)-positive patients with poorly-controlled disease, immunosuppressed, elderly, diabetic, and pregnant patients. Difficult-to-treat patients tend to have a higher number of visits than normal patients and have surgery as a treatment option in the model.
Patients considered normal in terms of their treatment were further divided into those with keratinised warts (firm, usually occurring on dry, hairy skin) and non-keratinised warts (soft and usually occurring on warm, moist, non-hair bearing skin). Patients with either classification of warts were split according to the treatments received, consisting of topical treatment (imiquimod or podophyllotoxin), destructive treatment (cryotherapy), or a combination. The number of GW cases accessing primary care was based on estimates of the total population, using population data from the Office of National Statistics (ONS, 2002–2010) for England and Wales,11 the General Register Office for Scotland (2002–2010),12 the Northern Ireland Statistics and Research Agency (2002–2011),13 and 2011 census data for England, Wales and Scotland.14 Population estimates for 2012 were calculated by fitting a linear trend on the available population data by jurisdiction. Rates for presentation of GW in primary care, the number of visits, and the rates of receipt of topical or destructive therapy were estimated using 2008–09 data from the THIN database.15 These rates were applied to the 2012 population estimates for each jurisdiction. The total number of GP visits for men and for women was
Figure 1. Proportion of (a) GW cases and (b) associated management costs in the UK and for each jurisdiction, by location of treatment and episode classification. Labels on each segment indicate the absolute case numbers (a) and costs in thousands (b).
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varied by 10% in sensitivity analyses. Patients presenting with GW in primary care, but not treated, were assumed to have been treated in GUM clinics. The number of GW cases treated in GUM clinics was based on KC60 diagnostic statistics. Data were obtained from the HPA for the UK and England;16 the Information Services Division for Scotland;17 the Communicable Disease Surveillance Centre for Wales;18 and the Public Health Agency for NI.19 At the time of the analysis, data were only available up to 2011 for England; 2009 for Scotland; 2010 for Wales and NI; and 2009 for the UK collectively. Data for the UK and each jurisdiction were extrapolated using polynomial regression equations to estimate the number of annual cases between 2000 and 2012. In the absence of long-term data for Wales, where only 5 years’ data were available, a regression equation could not be obtained so a linear fit was used. This approach was used to estimate the number of patients with first attack, persistent and recurrent GW cases. Where persistent and recurrent cases were grouped together separate estimates were derived by assuming the same distribution of persistent and recurrent cases as were observed in the UK as a whole.
A questionnaire, developed with two clinicians, was administered to four expert GUM consultants to estimate the number of visits and treatments based on the type of case, gender and type of wart (keratinised or non-keratinised), and for the patients classified as difficult-to-treat, which were all assumed to incur costs of a surgical procedure. The estimated mean number of visits was between 2.18 and 2.50 for non-complicated cases, depending on the episode type and therapy, and 10 for difficult-to-treat cases. These were used in base case analyses, and the upper and lower bounds of the range of clinicians’ estimates were used in sensitivity analyses as previously published.9 Unit costs (Table 1) were taken from NHS Payment by Results (PbR) reference cost schedules,20 the Personal Social Services Research Unit (PSSRU),21 and the British National Formulary (BNF).22 Topical treatment and cryotherapy costs were assumed to be included in the GUM clinic visit cost based on information from a GUM accounting authority. Podophyllotoxin is available as a cream as well as a solution, and in the case of podophyllotoxin use in primary care, the model assumed the same cost and
Table 1. Unit costs used to estimate the cost of managing genital warts (GW) in the UK. Cost items
Code
Unit cost (£)
Source
GUM Adult first attendance – single professional (WF01B)
360 (treatment function code)
133.00
Adult follow-up attendance – single professional (WF01A)
360 (treatment function code)
82.00
GP visit costs
10.8 b (Table number)
43.00
Outpatient attendance tariff, PbR arrangements for 2012–2013, Department of Health, 5 April 2013, Sheet: ‘‘2. OP Attendances’’.20 Outpatient attendance tariff, PbR arrangements for 2012–2013, Department of Health, 5 April 2013, Sheet: ‘‘2. OP Attendances’’.20 GP (with qualification) unit cost per surgery consultation lasting 11.7 minutes, including direct care staff costs. PSSRU (2012) p183.21
MA04B (HRG code)
1370.00
Outpatient attendance tariff, PbR arrangements for 2012–2013, Department of Health, 5 April 2013, Sheet: ‘‘01. APC & OPROC’’.20
–
48.39
–
12.38
12 sachet pack, BNF 65, BMJ Group and Pharmaceutical Press (2013).22 0.5% in alcoholic basis, 3 mL (with applicators), BNF 65, BMJ Group and Pharmaceutical Press (2013).22
Surgery costs Lower genital tract intermediate procedures without CC Drug costs Imiquimod (Aldara) Podophyllotoxin (Warticon solution)
CC: complications and comorbidities; PbR: payment by results; GP: general practitioner; GUM: genitourinary medicine; OP: outpatient; PSSRU: Personal Social Services Research Unit; BNF: British National Formulary; APC: admitted patient care; OPROC: outpatient procedure.
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Sensitivity analyses
Figure 2. Proportion of GW management costs incurred for men and women in the UK and for each jurisdiction. Labels on each segment indicate the absolute costs in thousands.
efficacy. For sensitivity analyses, unit costs were varied by 20%.
Results The model predicts that 220,875 people in the UK were treated for GW in 2012. Of these, 203,883 were treated in GUM clinics (including 33,134 referred from primary care) and 16,992 were treated in primary care. Of those treated in GUM clinics, 103,537 (50.8%) were first episodes, 69,707 (34.2%) were recurrent, and 30,639 (15.0%) were persistent cases (Figure 1a); 2071 patients treated for a first episode of GW in GUM clinics were classified as difficult-to-treat according to our criteria. The total UK management cost in 2012 was £58.44 million; £55.55 million for patients in GUM clinics and £2.89 million for patients in primary care (Figure 1b). In all, 56.2% of costs (£32.85 million) were associated with the treatment of GW in men (Figure 2). The average cost per patient was £265. These updated estimates represent an increase of 31,016 cases (16.3%) and £6.06 million (11.6%) on the 2010 estimate.9 Analysis by country estimated that 157,793, 7468, 7095, and 3621 people were treated for GW in England, Scotland, Wales, and NI, respectively, in 2012, with first episodes accounting for the largest proportion of cases and costs in each jurisdiction (Figure 1). Between 9.0% (in England) and 19.1% (in Scotland) of patients were treated in primary care. The total management cost in 2012 was estimated to be £41.74 million, £1.90 million, £1.87 million, and approximately £948,000 in England, Scotland, Wales, and NI, respectively. In all jurisdictions, men accounted for a greater proportion of costs than women (51.4%– 57.6%; Figure 2). The average cost per patient across
One-way sensitivity analyses were conducted to explore the impact of clinicians’ estimates (Figure 3a) and the unit costs used in the analysis (Figure 3b). Of the parameters tested, the cost of GW management in the UK was most sensitive to the proportion of patients which are deemed difficult to treat. In the base case, it was assumed that 2% of patients were difficult to treat. Using the upper bound of the range of clinicians’ estimates (8%) led to a 41.9% increase in total costs to £82.9 million, while the lower bound (0.05%) led to a 13.6% decrease. The next most important parameter was the maximum number of visits for normally treated warts. The model assumed that patients would make a maximum of five visits in the base case. Decreasing this to three visits led to an 8.2% decrease in costs, whilst increasing it to eight led to a 12.3% increase in costs. In terms of unit costs, the UK GW management cost was most sensitive to the cost of follow-up appointments. Varying this by 20% led to a 9.2% change in the total cost of GW management.
Discussion In its framework for sexual health improvement, the UK Department of Health (DH) has emphasised the importance of good individual sexual health as a key public health priority.23 GW are one of the most common STIs in the UK, with a significant epidemiological burden, particularly in those in their teens and early twenties.1 In the current analysis, the total UK cost of managing GW in 2012 was estimated at £58.44 million, 95% of which was incurred in GUM clinics. This is an update to a previous estimate of £52.4 million for 20109 and exceeds figures reported in earlier studies.2,6–8 These differences are primarily due to the inclusion of primary care costs, robust estimates of unit costs through PbR data, and the use of the most up-to-date surveillance data in the present analysis. This study estimated the full and up-to-date costs of GW management by UK jurisdiction, and, to our knowledge, is the first to do so. The analysis suggests that the financial implications of GW are substantial in all four jurisdictions, with management costs of £41.74 million in England, £1.90 million in Scotland, £1.87 million in Wales, and £948,000 in NI. These findings are validated by PHE STI data published since the construction of this model, which report 73,893 new GW diagnoses (first episodes) in GUM clinics in England in 2012,3 suggesting that our model overestimated the burden by just 7%.
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Figure 3. Tornado diagram illustrating results of sensitivity analyses for GW management costs in the UK in 2012. (a) Clinicians’ estimates were varied across the range of estimates obtained, and the total number of GP visits made by women and by men were each varied by þ/10%. (b) Costs obtained from PbR reference cost schedules, the PSSRU and the BNF were varied by þ/20%. Example interpretation (top line of (a), proportion of patients difficult to treat): using the upper bound of the range of clinicians’ estimates (8%) led to an increase in total costs to £82.9 million, while the lower bound (0.05%) led to a decrease in total costs to £50.5 million.
The DH has stated the need to ‘‘continue to work to reduce the rate of STIs using evidence-based preventative interventions and treatment initiatives’’.23 In addition to public health benefits, the current analysis suggests that prevention of GW could yield significant savings for the NHS. The quadrivalent HPV vaccine, which has been offered to all 12- to 13-year-old girls in the UK since September 2012, may be associated with a decline in GW cases in the coming years as these adolescents reach sexual debut. The impact of GW upon the health and well-being of patients has been demonstrated in recent studies suggesting that GW are associated with a reduction in quality of life, which may be most pronounced in adolescent girls.24,25 This demographic group is likely to
benefit most directly from the current HPV vaccination programme. Both the financial and quality of life burdens of GW should be recognised and appropriately quantified in order to understand the full value of quadrivalent HPV vaccination. The vaccine is not currently offered to boys as the majority are thought to be protected through herd immunity although current real-world evidence is inconclusive. The first published data demonstrated that in Australia a high-coverage girls’ immunisation programme was associated with a decline in GW in boys.26 However, more recent data from Denmark demonstrate that although the vaccination programme was successful, such indirect effects on boys were not seen.27 This is thought to be due to much higher rates of
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international travel in Europe than in a large, relatively isolated country such as Australia, particularly in adolescent and early adult years, when STI rates tend to be highest. In this sense, the UK is likely to be much more similar to Denmark and therefore the effect of herd immunity for the protection of boys is, in reality, likely to be limited.28 Additionally, such indirect effects are not, by definition, conferred to other high-risk groups such as men who have sex with men. Universal adolescent vaccination has already been introduced in a number of countries, including the USA,29 Canada,30 Australia,10 Austria,31 and the Saxony region of Germany.32 Extending HPV vaccination to boys may have an additive effect, further reducing the burden of GW. This is especially pertinent given that both the PHE surveillance data1,3 and the present analysis suggest that the burden of GW is higher in men. Our analysis is subject to a number of limitations. Firstly, estimates of treatment patterns were based on the opinions of four clinical experts. Further, there was some variability in their estimates, and the results of the analysis were shown to be sensitive to this uncertainty. Secondly, it was assumed that the treatment given, the unit costs of treatment, and the proportion of GW cases classified as difficult-to-treat were the same across jurisdictions. Thirdly, the number of GW cases estimated for the UK does not match the sum of GW cases in England, Wales, Scotland, and NI in some years. This is because the number of GW cases was extrapolated independently for each jurisdiction and for the UK, which led to differences in predicted trends across jurisdictions. Future research should focus on addressing these limitations, such as using administrative data to investigate the differences between treatment patterns in each jurisdiction. Nevertheless, our analysis suggests that the high epidemiological burden of GW in the UK is associated with significant costs in all four constituent nations. Continued routine use of the quadrivalent HPV vaccine, as well as extension of the programme to adolescent boys, may reduce this financial burden, and would align with the UK Government’s priorities around prevention. Declaration of Conflicting Interests The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: VC and SC are employees of Sanofi Pasteur MSD, which holds a marketing authorisation for one of the HPV vaccinations in use in the UK. RC and TL have received consultancy fees from Sanofi Pasteur MSD.
Funding The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded in full by Sanofi Pasteur MSD.
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