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

Models of cervical screening in the era of human papillomavirus vaccination

Karen Canfell

Cancer Epidemiology Research Unit, Cancer Council NSW, 153 Dowling Street, Woolloomooloo, NSW 2010, Australia; School of Public Health, University of Sydney, Sydney, NSW 2006, Australia. Email:

Sexual Health 7(3) 359-367
Submitted: 15 February 2010  Accepted: 28 May 2010   Published: 19 August 2010


Epidemiologic and economic evaluation using simulation modelling can support complex policy decisions, and is an important tool in predicting the future interaction between human papillomavirus vaccination and cervical screening. Several categories of screening program evaluation are of interest, including: (1) changes to screening considered over the short term, over which the effects of vaccination should be confined to the youngest age groups (<30 years old); (2) the medium and long-term effect of vaccination on the screening program; and (3) changes to screening in context of vaccination. This review considers some of the policy questions in each category and discusses the modelling implications, with particular focus on the Australian context.

Additional keywords: Australia, Pap smear, simulation modelling.


[1]  Australian Institute of Health and Welfare. Cervical Screening in Australia 2006–2007. Report No.: Cat. No. CAN 43. Canberra: Australian Institute of Health and Welfare; 2009.

[2]  Canfell K Sitas F Beral V 2006 Cervical cancer in Australia and the United Kingdom: comparison of screening policy and uptake, and cancer incidence and mortality. Med J Aust 185 482 6

[3]  National Health and Medical Research Council. Screening to prevent cervical cancer: guidelines for the management of asymptomatic women with screen detected abnormalities. Canberra: NHMRC; 2005. Available online at: [verified July 2010].

[4]  International Agency for Research on Cancer. GLOBOCAN 2002. Lyon: IARC; 2005. Available online at: [verified July 2010].

[5]  Curado MP , Edwards B , Shin HR , Storm H , Frelay J , Heanue M et al Cancer incidence in five continents, Vol. IX. Report No.: IARC Scientific Publications No. 160. Lyon: IARC; 2007.

[6]  International Agency for Research on Cancer. WHO mortality database extracted from the World Health Organization (WHO) Databank. Lyon: IARC; 2005. Available online at: [verified July 2010].

[7]  Neville AM Quinn MA 2005 An alternative cost effectiveness analysis of ThinPrep in the Australian setting. Aust N Z J Obstet Gynaecol 45 289 94 doi:10.1111/j.1479-828X.2005.00413.x

[8]  Anderson R Haas M Shanahan M 2008 The cost-effectiveness of cervical screening in Australia: what is the impact of screening at different intervals or over a different age range? Aust N Z J Public Health 32 43 52 doi:10.1111/j.1753-6405.2008.00165.x

[9]  Kulasingam S Connelly L Conway E Hocking JS Myers E Regan DG et al 2007 A cost-effectiveness analysis of adding a human papillomavirus vaccine to the Australian National Cervical Cancer Screening Program. Sex Health 4 165 75 doi:10.1071/SH07043

[10]  Medical Services Advisory Committee. Automation assisted and liquid based cytology for cervical cancer screening. MSAC reference 1122, Assessment report. Canberra: MSAC; 2009. Available online at:$File/1122_MSAC_Assessment_Report.pdf [verified July 2010].

[11]  Medical Services Advisory Committee. Human papillomavirus triage test for women with possible or definite low-grade squamous intraepithelial lesions. Canberra: MSAC; 2009. Available online at:$File/39_MSAC_Assessment_Report.pdf [verified July 2010].

[12]  Drummond MF , Sculpher MJ , Torrance GW , O’Brien BJ , Stoddart GL . Methods for the economic evaluation of health care programmes. New York: Oxford University Press; 2005.

[13]  Kim JJ Kuntz KM Stout NK Mahmud S Villa LL Franco EL et al 2007 Multiparameter calibration of a natural history model of cervical cancer. Am J Epidemiol 166 137 50 doi:10.1093/aje/kwm086

[14]  van de Velde N Brisson M Boily MC 2007 Modeling human papillomavirus vaccine effectiveness: quantifying the impact of parameter uncertainty. Am J Epidemiol 165 762 75 doi:10.1093/aje/kwk059

[15]  Goldhaber-Fiebert JD Stout NK Ortendahl J Kuntz KM Goldie SJ Salomon JA 2007 Modeling human papillomavirus and cervical cancer in the United States for analyses of screening and vaccination. Popul Health Metr 5 11 doi:10.1186/1478-7954-5-11

[16]  McIndoe WA McLean MR Jones RW Mullins PR 1984 The invasive potential of carcinoma in situ of the cervix. Obstet Gynecol 64 451 8

[17]  McCredie MR Sharples KJ Paul C Baranyai J Medley G Jones RW et al 2008 Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol 9 425 34

[18]  Howard K Salkeld G McCaffery K Irwig L 2008 HPV triage testing or repeat Pap smear for the management of atypical squamous cells (ASCUS) on Pap smear: is there evidence of process utility? Health Econ 17 593 605 doi:10.1002/hec.1278

[19]  Dickinson JA 2002 Cervical screening: time to change the policy. Med J Aust 176 547 50

[20]  IARC Working Group on the Evaluation of Cancer. IARC handbooks of cancer prevention volume 10: cervix cancer screening (10th edition). Lyon: IARC Press; 2005.

[21]  IARC 1986 Screening for squamous cervical cancer: duration of low risk after negative results of cervical cytology and its implication for screening policies. BMJ 293 659 64

[22]  Sasieni P Adams J Cuzick J 2003 Benefit of cervical screening at different ages: evidence from the UK audit of screening histories. Br J Cancer 89 88 93 doi:10.1038/sj.bjc.6600974

[23]  Sasieni P Castanon A Cuzick J 2009 Effectiveness of cervical screening with age: population based case-control study of prospectively recorded data. BMJ 339 b2968 doi:10.1136/bmj.b2968

[24]  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

[25]  Cuzick J Arbyn M Sankaranarayanan R Tsu V Ronco G Mayrand MH et al 2008 Overview of human papillomavirus-based and other novel options for cervical cancer screening in developed and developing countries. Vaccine 26 Suppl. 10 K29 K41 doi:10.1016/j.vaccine.2008.06.019

[26]  Canfell K Barnabas R Patnick J Beral V 2004 The predicted effect of changes in cervical screening practice in the UK: results from a modelling study. Br J Cancer 91 530 6 doi:10.1038/sj.bjc.6602002

[27]  Australian Bureau of Statistics (ABS). National Health Survey, summary of results, Australia, 2004–05. Cat. No. 4364.0. Canberra: ABS; 2006.

[28]  Medical Services Advisory Committee. Completed assessments. 4-1-2010. Canberra: MSAC. Available online at: [accessed February 2010].

[29]  NPAAC. Performance measures for Australian laboratories reporting cervical cytology. Canberra: Department of Health and Ageing, National Pathology Accreditation Advisory Council; 2006.

[30]  Williams AR 2006 Liquid-based cytology and conventional smears compared over two 12-month periods. Cytopathology 17 82 5 doi:10.1111/j.1365-2303.2006.00339.x

[31]  Cuzick J Castanon A Sasieni P 2010 Predicted impact of vaccination against human papillomavirus 16/18 on cancer incidence and cervical abnormalities in women aged 20–29 in the UK. Br J Cancer 102 933 39 doi:10.1038/sj.bjc.6605528

[32]  Brotherton J Deeks S Campbell-Lloyd S Misrachi A Passaris I Peterson K et al 2008 Interim estimates of human papillomavirus vaccination coverage in the school-based program in Australia. Commun Dis Intell 32 457 61

[33]  Future II Study Group 2007 Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med 356 1915 27

[34]  Hildesheim A Herrero R Wacholder S Rodriguez AC Solomon D Bratti MC et al 2007 Effect of human papillomavirus 16/18 L1 viruslike particle vaccine among young women with preexisting infection: a randomized trial. JAMA 298 743 53 doi:10.1001/jama.298.7.743

[35]  Riethmuller D , for the Quadrivalent HPV Vaccine Investigators. Quadrivalent HPV 6/11/16/18 vaccine efficacy against persistent infection or disease in subjects with prior HPV vaccine HPV type infection. Abstract presented at EUROGIN (SS 3–6). EUROGIN 2010 Meeting, Monte Carlo, Monaco 17–20 February 2010.

[36]  Smith MA Canfell K Brotherton JM Lew JB Barnabas RV 2008 The predicted impact of vaccination on human papillomavirus infections in Australia. Int J Cancer 123 1854 63 doi:10.1002/ijc.23633

[37]  Anderson RM Garnett GP 2000 Mathematical models of the transmission and control of sexually transmitted diseases. Sex Transm Dis 27 636 43 doi:10.1097/00007435-200011000-00012

[38]  Garnett GP 2002 An introduction to mathematical models in sexually transmitted disease epidemiology. Sex Transm Infect 78 7 12 doi:10.1136/sti.78.1.7

[39]  Regan DG Philp 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

[40]  Garland SM , Brotherton J . The prevalence of human papillomavirus infection in Australia: analysis of data from the Women, Human Papillomavirus prevalence, Indigenous, Non-Indigenous, Urban, Rural (WHINURS) study. Proceedings of the 24th International Papillomavirus Society Conference, Beijing, China; 2007 Nov 9.

[41]  Schiffman M 2007 Integration of human papillomavirus vaccination, cytology, and human papillomavirus testing. Cancer 111 145 53 doi:10.1002/cncr.22751

[42]  Mayrand MH Duarte-Franco E Rodrigues I Walter SD Hanley J Ferenczy A et al 2007 Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. N Engl J Med 357 1579 88 doi:10.1056/NEJMoa071430

[43]  Bulkmans NW Berkhof J Rozendaal L van Kemenade FJ Boeke AJ Bulk S et al 2007 Human papillomavirus DNA testing for the detection of cervical intraepithelial neoplasia grade 3 and cancer: 5-year follow-up of a randomised controlled implementation trial. Lancet 370 1764 72 doi:10.1016/S0140-6736(07)61450-0

[44]  Naucler P Ryd W Tornberg S Strand A Wadell G Elfgren K et al 2007 Human papillomavirus and Papanicolaou tests to screen for cervical cancer. N Engl J Med 357 1589 97 doi:10.1056/NEJMoa073204

[45]  Cuzick J Szarewski A Cubie H Hulman G Kitchener H Luesley D et al 2003 Management of women who test positive for high-risk types of human papillomavirus: the HART study. Lancet 362 1871 6 doi:10.1016/S0140-6736(03)14955-0

[46]  Ronco G Giorgi-Rossi P Carozzi F Confortini M Palma PD Del MA et al 2010 Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial. Lancet Oncol 11 249 57 doi:10.1016/S1470-2045(09)70360-2

[47]  Kitchener HC Almonte M Thomson C Wheeler P Sargent A Stoykova B et al 2009 HPV testing in combination with liquid-based cytology in primary cervical screening (ARTISTIC): a randomised controlled trial. Lancet Oncol 10 672 82 doi:10.1016/S1470-2045(09)70156-1

[48]  Kitchener HC Almonte M Gilham C Dowie R Stoykova B Sargent A et al 2009 ARTISTIC: a randomised trial of human papillomavirus (HPV) testing in primary cervical screening. Health Technol Assess 13 1 150 iii–iv.

[49]  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

[50]  Schiffman M Castle PE Jeronimo J Rodriguez AC Wacholder S 2007 Human papillomavirus and cervical cancer. Lancet 370 890 907

[51]  Eder PS Lou J Huff J Macioszek J 2009 The next-generation Hybrid Capture High-Risk HPV DNA assay on a fully automated platform. J Clin Virol 45 S85 92 doi:10.1016/S1386-6532(09)70013-7

[52]  Coutlee F Mayrand MH Roger M Franco EL 2009 Detection and typing of human papillomavirus nucleic acids in biological fluids. Public Health Genom 12 308 18 doi:10.1159/000214921

[53]  Day SP Hudson A Mast A Sander T Curtis M Olson S et al 2009 Analytical performance of the Investigational Use Only Cervista HPV HR test as determined by a multi-center study. J Clin Virol 45 S63 72 doi:10.1016/S1386-6532(09)70010-1

[54]  Kurtycz DF Smith M He R Miyazaki K Shalkham J 2010 Comparison of methods trial for high-risk HPV. Diagn Cytopathol 38 104 8

[55]  Thai H Rangwala S Gay T Keating K McLeod S Nazarenko I et al 2009 An HPV 16, 18, and 45 genotyping test based on Hybrid Capture technology. J Clin Virol 45 Suppl. 1 S93 7

[56]  Tsoumpou I Arbyn M Kyrgiou M Wentzensen N Koliopoulos G Martin-Hirsch P et al 2009 p16(INK4a) immunostaining in cytological and histological specimens from the uterine cervix: a systematic review and meta-analysis. Cancer Treat Rev 35 210 20 doi:10.1016/j.ctrv.2008.10.005

[57]  Koukari A . Renewal of the National Cervical Screening Program. Talk at Preventing Cervical Cancer 2009, Melbourne, March, 2009.

Export Citation