Sexual Health Sexual Health Society
Publishing on sexual health from the widest perspective
RESEARCH ARTICLE

A cost-effectiveness analysis of adding a human papillomavirus vaccine to the Australian National Cervical Cancer Screening Program

Shalini Kulasingam A J , Luke Connelly B , Elizabeth Conway C , Jane S. Hocking D , Evan Myers E , David G. Regan F , David Roder G , Jayne Ross H and Gerard Wain I

A Duke University, Center for Clinical Health Policy Research, Durham, NC 27710, USA.

B The University of Queensland, Mayne Medical School, Herston, Qld 4006, Australia.

C CSL Limited, Parkville, Vic. 3052, Australia.

D The University of Melbourne, Parkville, Vic. 3010, Australia.

E Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710, USA.

F National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Darlinghurst, NSW 2010, Australia.

G Group Executive, Research and Information Science, The Cancer Council South Australia, Unley, SA 5061, Australia.

H Jayne Ross & Associates, Cheltenham, NSW 2118, Australia.

I Department of Gynaecological Oncology, Westmead Hospital, Westmead, NSW 2145, Australia.

J Corresponding author. Email: kulas002@mc.duke.edu

Sexual Health 4(3) 165-175 http://dx.doi.org/10.1071/SH07043
Submitted: 19 June 2007  Accepted: 22 June 2007   Published: 23 August 2007

Abstract

Background: The cost-effectiveness of adding a human papillomavirus (HPV) vaccine to the Australian National Cervical Screening Program compared to screening alone was examined. Methods: A Markov model of the natural history of HPV infection that incorporates screening and vaccination was developed. A vaccine that prevents 100% of HPV 16/18-associated disease, with a lifetime duration of efficacy and 80% coverage offered through a school program to girls aged 12 years, in conjunction with current screening was compared with screening alone using cost (in Australian dollars) per life-year (LY) saved and quality-adjusted life-year (QALY) saved. Sensitivity analyses included determining the cost-effectiveness of offering a catch-up vaccination program to 14–26-year-olds and accounting for the benefits of herd immunity. Results: Vaccination with screening compared with screening alone was associated with an incremental cost-effectiveness ratio (ICER) of $51 103 per LY and $18 735 per QALY, assuming a cost per vaccine dose of $115. Results were sensitive to assumptions about the duration of vaccine efficacy, including the need for a booster ($68 158 per LY and $24 988 per QALY) to produce lifetime immunity. Accounting for herd immunity resulted in a more attractive ICER ($36 343 per LY and $13 316 per QALY) for girls only. The cost per LY of vaccinating boys and girls was $92 052 and the cost per QALY was $33 644. The cost per LY of implementing a catch-up vaccination program ranged from $45 652 ($16 727 per QALY) for extending vaccination to 14-year-olds to $78 702 ($34 536 per QALY) for 26-year-olds. Conclusions: These results suggest that adding an HPV vaccine to Australia’s current screening regimen is a potentially cost-effective way to reduce cervical cancer and the clinical interventions that are currently associated with its prevention via screening alone.


References

[1]  Department of Health and Aging Australian Government. The National Cervical Screening Program. Facts and key statistics. 2007. Available from: http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/Content/facts [accessed 8 June, 2007]

[2]  Australian Institute of Health and Welfare (AIHW). Cervical screening in Australia 2002–3. Cancer Series No. 31, Canberra: AIHW; 2005.

[3]  Report of the Evaluation Steering Committee. The interim evaluation of the organised approach to preventing cancer of the cervix 1991–95. Report No. 27. Canberra: Australian Government Publishing Service; 1995.

[4]  Bosch FX Manos MM Munoz N Sherman M Jansen AM Peto J et al 1995 Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) study group. J Natl Cancer Inst 87 796 802 doi:10.1093/jnci/87.11.796

[5]  Munoz N Bosch FX de Sanjose S Herrero R Castellsague X Shah KV et al 2003 Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 348 518 27 doi:10.1056/NEJMoa021641

[6]  Clifford GM Smith JS Plummer M Munoz N Franceschi S 2003 Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis. Br J Cancer 88 63 73 doi:10.1038/sj.bjc.6600688

[7]  Koutsky LA Ault KA Wheeler CM Brown DR Barr E Alvarez FB et al 2002 A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 347 1645 51 doi:10.1056/NEJMoa020586

[8]  Villa LL Costa RL Petta CA Andrade RP Ault KA Giuliano AR et al 2005 Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol 6 271 8 doi:10.1016/S1470-2045(05)70101-7

[9]  Harper DM Franco EL Wheeler C Ferris DG Jenkins D Schuind A et al 2004 Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 364 1757 65 doi:10.1016/S0140-6736(04)17398-4

[10]  Harper DM Franco EL Wheeler CM Moscicki AB Romanowski B Roteli-Martins CM et al 2006 Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 367 1247 55 doi:10.1016/S0140-6736(06)68439-0

[11]  Department of Health and Aging Australian Government. Australian Government funding of Gardasil. 2006. Available from: http://www.health.gov.au/internet/wcms/publishing.nsf/Content/4754B33584405E06CA2572220008CFA8/$File/Gardasilfunding-factsheet.pdf [accessed 8 June, 2007]

[12]  Clifford GM Rana RK Franceschi S Smith JS Gough G Pimenta JM 2005 Human papillomavirus genotype distribution in low-grade cervical lesions: comparison by geographic region and with cervical cancer. Cancer Epidemiol Biomarkers Prev 14 1157 64 doi:10.1158/1055-9965.EPI-04-0812

[13]  Clifford GM Smith JS Aguado T Franceschi S 2003 Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: a meta-analysis. Br J Cancer 89 101 5 doi:10.1038/sj.bjc.6601024

[14]  McCrory DC , Matchar DB , Bastian L , Datta S , Hasselblad V , Hickey J , et al Evaluation of cervical cytology. Evidence Report/Technology Assessment No. 5 (Prepared by Duke University under Contract No. 290–97–0014). AHCPR Publication No. 99–E010. Rockville, MD: Agency for Health Care Policy and Research; 1999.

[15]  Myers ER McCrory DC Nanda K Bastian L Matchar DB 2000 Mathematical model for the natural history of human papillomavirus infection and cervical carcinogenesis. Am J Epidemiol 151 1158 71

[16]  Schiffman M Kjaer SK 2003 Chapter 2: Natural history of anogenital human papillomavirus infection and neoplasia. J Natl Cancer Inst Monogr 14 9


[17]  Sellors JW Karwalajtys TL Kaczorowski J Mahony JB Lytwyn A Chong S et al 2003 Incidence, clearance and predictors of human papillomavirus infection in women. CMAJ 168 421 5


[18]  Munoz N Mendez F Posso H Molano M van den Brule AJ Ronderos M et al 2004 Incidence, duration, and determinants of cervical human papillomavirus infection in a cohort of Colombian women with normal cytological results. J Infect Dis 190 2077 87
doi:10.1086/425907

[19]  Jacobs MV Walboomers JM Snijders PJ Voorhorst FJ Verheijen RH Fransen-Daalmeijer N et al 2000 Distribution of 37 mucosotropic HPV types in women with cytologically normal cervical smears: the age-related patterns for high-risk and low-risk types. Int J Cancer 87 221 7 doi:10.1002/1097-0215(20000715)87:2<221::AID-IJC11>3.0.CO;2-2

[20]  Peto J Gilham C Deacon J Taylor C Evans C Binns W et al 2004 Cervical HPV infection and neoplasia in a large population-based prospective study: the Manchester cohort. Br J Cancer 91 942 53

[21]  Schlecht NF Platt RW Duarte-Franco E Costa MC Sobrinho JP Prado JC et al 2003 Human papillomavirus infection and time to progression and regression of cervical intraepithelial neoplasia. J Natl Cancer Inst 95 1336 43


[22]  Hoyer H Scheungraber C Kuehne-Heid R Teller K Greinke C Leistritz S et al 2005 Cumulative 5-year diagnoses of CIN2, CIN3 or cervical cancer after concurrent high-risk HPV and cytology testing in a primary screening setting. Int J Cancer 116 136 43
doi:10.1002/ijc.20955

[23]  Winer RL Kiviat NB Hughes JP Adam DE Lee SK Kuypers JM et al 2005 Development and duration of human papillomavirus lesions, after initial infection. J Infect Dis 191 731 8 doi:10.1086/427557

[24]  Giuliano AR Harris R Sedjo RL Baldwin S Roe D Papenfuss MR et al 2002 Incidence, prevalence, and clearance of type-specific human papillomavirus infections: the Young Women’s Health Study. J Infect Dis 186 462 9 doi:10.1086/341782

[25]  Yokoyama M Iwasaka T Nagata C Nozawa S Sekiya S Hirai Y et al 2003 Prognostic factors associated with the clinical outcome of cervical intraepithelial neoplasia: a cohort study in Japan. Cancer Lett 192 171 9 doi:10.1016/S0304-3835(02)00715-2

[26]  Sastre-Garau X Cartier I Jourdan-Da Silva N De Cremoux P Lepage V Charron D 2004 Regression of low-grade cervical intraepithelial neoplasia in patients with HLA-DRB1*13 genotype. Obstet Gynecol 104 751 5

[27]  Kataja V Syrjanen K Mantyjarvi R Vayrynen M Syrjanen S Saarikoski S et al 1989 Prospective follow-up of cervical HPV infections: life table analysis of histopathological, cytological and colposcopic data. Eur J Epidemiol 5 1 7
doi:10.1007/BF00145037

[28]  Matsumoto K Yasugi T Oki A Fujii T Nagata C Sekiya S et al 2006 IgG antibodies to HPV16, 52, 58 and 6 L1-capsids and spontaneous regression of cervical intraepithelial neoplasia. Cancer Lett 231 309 13 doi:10.1016/j.canlet.2005.02.023

[29]  De Aloysio D Miliffi L Iannicelli T Penacchioni P Bottiglioni F 1994 Intramuscular interferon-beta treatment of cervical intraepithelial neoplasia II associated with human papillomavirus infection. Acta Obstet Gynecol Scand 73 420 4

[30]  Brestovac B Harnett GB Smith DW Shellam GR Frost FA 2005 Human papillomavirus genotypes and their association with cervical neoplasia in a cohort of Western Australian women. J Med Virol 76 106 10
doi:10.1002/jmv.20330

[31]  Chen S O’Sullivan H Tabrizi SN Fairley CK Quinn MA Garland SM 1999 Prevalence and genotyping of HPV in cervical cancer among Australian women. Int J Gynaecol Obstet 67 163 8 doi:10.1016/S0020-7292(99)00167-8

[32]  Liu JH Huang X Liao GW Li JD Li YF Li MD et al 2003 [Human papillomavirus infection and other risk factors for cervical cancer in Chinese and Australian patients] Zhonghua Yi Xue Za Zhi 83 748 52

[33]  Stevens MP Tabrizi SN Quinn MA Garland SM 2006 Human papillomavirus genotype prevalence in cervical biopsies from women diagnosed with cervical intraepithelial neoplasia or cervical cancer in Melbourne, Australia. Int J Gynecol Cancer 16 1017 24
doi:10.1111/j.1525-1438.2006.00453.x

[34]  Australian Institute of Health and Welfare (AIHW). General Record of Incidence of Mortality (GRIM) Books. 2005. Available from: http://www.aihw.gov.au/mortality/data/grim_books_national.cfm [accessed 8 June, 2007]

[35]  Australian Institute of Health and Welfare (AIHW). Separation, patient day and average length of stay statistics by Australian Refined Diagnosis Related Group (AR-DRG) Version 5.0/5.1. Australia, 1998–99 to 2004–05. Canberra: AIHW; 2005.

[36]  South Australian Cancer Registry. Epidemiology of cancer in South Australia. Incidence, mortality and survival 1977 to 1999. Incidence and mortality 1999. Adelaide: Openbook Publishers; 2000.

[37]  Davy MLJ Dodd TJ Luke CJ Roder DM 2003 Cervical cancer: effect of glandular cell type on prognosis, treatment, and survival. Obstet Gynecol 101 38 45 doi:10.1016/S0029-7844(02)02275-5

[38]  Cuzick J Clavel C Petry KU Meijer CJ Hoyer H Ratnam S et al 2006 Overview of the European and North American studies on HPV testing in primary cervical cancer screening. Int J Cancer 119 1095 101 doi:10.1002/ijc.21955

[39]  Morrell S Mamoon H O’Callaghan J Taylor R Ross J Wain G 2002 Early cervical cancer rescreening. J Med Screen 9 26 32 doi:10.1136/jms.9.1.26

[40]  Medical Services Advisory Committee. Human papillomavirus testing in women with cytological prediction of low-grade abnormality: assessment report 12b. Canberra: MSAC; 2002

[41]  National Health and Medical Research Council. National Cervical Screening Program. Screening to prevent cervical cancer: guidelines for the management of asymptomatic women with screen detected abnormalities. Canberra: NHMRC; 2005

[42]  Gynaecological Oncology Study Group. Gynaecological oncology clinical practice guidelines. Sydney: GMTT; 2004.

[43]  Blomfield P Davy M Hammond I Wain G 2005 The new NH&MRC guidelines for management of abnormal Pap smears in asymptomatic Australian women. Obstet Gynecol 7 25 7

[44]  Skinner R Nolan T. 2001 Adolescent hepatitis B immunisation – should it be the law? Aust NZ J Public Health 25 230 3


[45]  Villa LL Ault KA Giuliano AR Costa RL Petta CA Andrade RP et al 2006 Immunologic responses following administration of a vaccine targeting human papillomavirus types 6, 11, 16, and 18. Vaccine 24 5571 83
doi:10.1016/j.vaccine.2006.04.068

[46]  Regan DG Philip DJ Hocking JS Law MG 2007 Modelling the population-level impact of vaccination on the transmission of human papillomavirus type 16 in Australia. Sex Health 4 147 63 doi:10.1071/SH07042

[47]  Medicare Australia. Australian Government. Medicare benefits schedule. 2006. Available from: http://www.medicareaustralia.gov.au/providers/health_statistics/statistical_reporting/medicare.htm [accessed 8 June, 2007]

[48]  Department of Health and Aging Australian Government. Medicare statistics – March quarter 2006. Group B Tables – selected statistics by broad type of service. 2006. Available from: http://www.health.gov.au/internet/wcms/publishing.nsf/Content/medstat-mar06-analysis-b [accessed 8 June, 2007]

[49]  Municipal Association of Victoria. Cost of Victorian local government immunisation services; Melbourne: MAV; 2004.

[50]  Myers ER , Green S , Lipkus I . Patient preferences for health states related to HPV infection. Visual analog scales versus time trade-off elicitation. Proceedings of the 21st International Papillomavirus Conference, 2004 February 20–27; Mexico City, Mexico.

[51]  Pharmaceutical Benefits Advisory Committee. Guidelines for preparing submissions to the Pharmaceutical Benefits Advisory Committee (PBAC). Version 41. Canberra: PBAC; 2006

[52]  Goldie SJ Kohli M Grima D Weinstein MC Wright TC Bosch FX et al 2004 Projected clinical benefits and cost-effectiveness of a human papillomavirus 16/18 vaccine. J Natl Cancer Inst 96 604 15

[53]  Kulasingam SL Myers ER 2003 Potential health and economic impact of adding a human papillomavirus vaccine to screening programs. JAMA 290 781 9
doi:10.1001/jama.290.6.781

[54]  Barnabas RV Laukkanen P Koskela P Kontula O Lehtinen M Garnett GP 2006 Epidemiology of HPV 16 and cervical cancer in Finland and the potential impact of vaccination: mathematical modelling analyses. PLoS Med 3 e138 doi:10.1371/journal.pmed.0030138

[55]  Lehtinen M Apter D Dubin G Kosunen E Isaksson R Korpivaara EL et al 2006 Enrolment of 22 000 adolescent women to cancer registry follow-up for long-term human papillomavirus vaccine efficacy: guarding against guessing. Int J STD AIDS 17 517 21 doi:10.1258/095646206778145550

[56]  Pharmaceutical Benefits Scheme. Department of Health and Aging. Australian Government. Government funds Gardasil. 2006. Available from: http://www.pbs.gov.au/html/healthpro/news/article?id=NEWS-2006-11-29-Aust_Govt_Funds_Gardasil.xml [accessed 8 June 2007]

[57]  National Institute for Clinical Excellence. Guide to the methods of technology appraisal. London: National Institute for Clinical Excellence; 2004.

[58]  Gold MR , Siegel JE , Russell LB , Weinstein MC , eds. Cost-effectiveness in health and medicine. New York: Oxford University Press; 1996.

[59]  Dasbach EJ Elbasha EH Insinga RP 2006 Mathematical models for predicting the epidemiologic and economic impact of vaccination against human papillomavirus infection and disease. Epidemiol Rev 28 88 100 doi:10.1093/epirev/mxj006

[60]  Elbasha EH Dasbach EJ Insinga RP 2007 Model for assessing human papillomavirus vaccination strategies. Emerg Infect Dis 13 28 41

[61]  Taira AV Neukermans CP Sanders GD 2004 Evaluating human papillomavirus vaccination programs. Emerg Infect Dis 10 1915 23




Export Citation