HPV Screening and Vaccination Strategies in an Unscreened Population: A Mathematical Modeling Study

  • Rachael M. Milwid
  • Federico Frascoli
  • Marc Steben
  • Jane M. Heffernan
Special Issue: Mathematical Epidemiology


Human papillomavirus (HPV), a sexually transmitted infection, is the necessary cause of cervical cancer, the third most common cancer affecting women worldwide. Prevention and control strategies include vaccination, screening, and treatment. While HPV prevention and control efforts are important worldwide, they are especially important in low-income areas with a high infection rate or high rate of cervical cancer. This study uses mathematical modeling to explore various vaccination and treatment strategies to control for HPV and cervical cancer while using Nepal as a case study. Two sets of deterministic models were created with the goal of understanding the impact of various prevention and control strategies. The first set of models examines the relative importance of screening and vaccination in an unscreened population, while the second set examines various screening scenarios. Partial rank correlation coefficients confirm the importance of screening and treatment in the reduction of HPV infections and cancer cases even when vaccination uptake is high. Results also indicate that less expensive screening technologies can achieve the same overall goal as more expensive screening technologies.


Mathematical epidemiology HPV Vaccination Screening 


  1. Alsaleh AA, Gumel AB (2014) Dynamics analysis of a vaccination model for HPV transmission. J Biol Syst 22(04):555–599MathSciNetCrossRefzbMATHGoogle Scholar
  2. Atkinson W, Wolfe S, Hamborsky J (2012) Epidemiology and prevention of vaccine-preventable diseases. The pink book: course textbook-12th edition. Education, Information and Partnership Branch, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and PreventionGoogle Scholar
  3. Blower SM, Dowlatabadi H (1994) Sensitivity and uncertainty analysis of complex models of disease transmission: an HIV model, as an example. Int Stat Rev 62:229–243CrossRefzbMATHGoogle Scholar
  4. Bosch F, Tsu V, Vorsters A, Damme PV, Kane M (2012) Reframing cervical cancer prevention. Expanding the field towards prevention of human papillomavirus infections and related diseases. Vaccine 30(S5):F1–F11CrossRefGoogle Scholar
  5. Brisson M, Laprise JF, Chesson HW, Drolet M, Malagón T, Boily MC, Markowitz LE (2016) Health and economic impact of switching from a 4-valent to a 9-valent HPV vaccination program in the United States. J Natl Cancer Inst 108(1):djv282CrossRefGoogle Scholar
  6. Brotherton JM, Jit M, Gravitt PE, Brisson M, Kreimer AR, Pai SI, Fakhry C, Monsonego J, Franceschi S (2016) Eurogin roadmap 2015: How has HPV knowledge changed our practice: vaccines. Int J Cancer 139(3):510–517CrossRefGoogle Scholar
  7. Bruni L, Barrionuevo-Rosas L, Albero G, Aldea M, Serrano B, Valencia S, Brotons M, Mena M, Cosano R, Muñoz J, Bosch F, de Sanjosé S, Castellsagué X (2015) Human papillomavirus and related diseases in Nepal. Summary report, ICO Information Centre on HPV and Cancer (HPV Information Centre)Google Scholar
  8. Castellsagué X (2008) Natural history and epidemiology of HPV infection and cervical cancer. Gynecol Oncol 110(3):S4–S7CrossRefGoogle Scholar
  9. Centers for Disease Control and Prevention (2015) HPV vaccine information for clinicians-fact sheet. Accessed 1 June 2015
  10. Crawford B, Kribs-Zaleta C (2009) The impact of vaccination and co-infection on HPV and cervical cancer. Discrete Contin Dyn Syst Ser B 12(2):279–304MathSciNetCrossRefzbMATHGoogle Scholar
  11. Dawar M, Deeks S, Dobson S (2007) Human papillomavirus vaccines launch a new era in cervical cancer prevention. Can Med Assoc J 177(5):456–461CrossRefGoogle Scholar
  12. de Velde NV, Brisson M, Bolly MC (2007) Modeling human papillomavirus vaccine effectiveness: quantifying the impact of parameter uncertainty. Am J Epidemiol 165(7):762–775CrossRefGoogle Scholar
  13. Diekmann O, Heesterbeek J, Roberts M (2009) The construction of next-generation matrices for compartmental epidemic models. J R Soc Interface 7:873–885CrossRefGoogle Scholar
  14. Dinshaw K, Edmunds J, Frazer I, Garcia P, Kahn J, Markowitz L, Muoz N, Ndumbe P, Pitisuttithum P, Beutels P, Chirenje M, Kahn J, Swati LB, You-Lin Q (2008) Human papillomavirus (HPV) vaccine background paper. Accessed 1 June 2015
  15. Dockter J, Schroder A, Hill C, Guzenski L, Monsonego J, Giachetti C (2009) Clinical performance of the APTIMA® HPV assay for the detection of high-risk HPV and high-grade cervical lesions. J Clin Virol 45(S1):S55–S61CrossRefGoogle Scholar
  16. Drolet M, Laprise JF, Boily MC, Franco E, Brisson M (2014) Potential cost-effectiveness of the nonavalent human papillomavirus (HPV) vaccine. Int J Cancer 134(9):2264–2268CrossRefGoogle Scholar
  17. Einstein M, Baron M, Levin M, Chatterjee A, Edwards R, Zepp F, Carletti I, Dessy F, Trofa A, Schuind A, Dubin G (2009) Comparison of the immunogenicity and safety of Cervarix\(^{\rm TM}\) and Gardasil\(^{{\textregistered }}\) human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18–45 years. Hum Vaccines 5(10):705–719CrossRefGoogle Scholar
  18. Elbasha E, Dasbach E, Insinga R (2007) Model for assessing human papillomavirus vaccination strategies. Emerg Infect Dis 13(1):28–41CrossRefGoogle Scholar
  19. Garnett G, Kim J, French K, Goldie S (2006) Chapter 21: modelling the impact of HPV vaccines on cervical cancer and screening programmes. Vaccine 24S3:178–186CrossRefGoogle Scholar
  20. Ghosh S, Seth S, Paul J, Rahman R, Chattopadhyay S, Bhadra D (2014) Evaluation of Pap smear, high risk HPV DNA testing in detection of cervical neoplasia with colposcopy guided or conventional biopsy as gold standard. Int J Healthc Biomed Res 2(2):192–197Google Scholar
  21. Goldie SJ, Grima D, Kohli M, Wright TC, Weinstein M, Franco E (2003) A comprehensive natural history model of HPV infection and cervical cancer to estimate the clinical impact of a prophylactic HPV-16/18 vaccine. Int J Cancer 106(6):896–904CrossRefGoogle Scholar
  22. Goldie S, Gaffikin L, Goldhaber-Fiebert J, Gordillo-Tobar A, Levin C, Mahé C, Wright T (2005) Cost-effectiveness of cervical-cancer screening in five developing countries. N Engl J Med 353(20):2158–2168CrossRefGoogle Scholar
  23. Government of Nepal (2014) National population and housing census 2011Google Scholar
  24. Government of Nepal (2014) Central Bureau of statistics: statistical pocket book of NepalGoogle Scholar
  25. Gravitt P, Paul P, Katki H, Vendantham H, Ramakrishna G, Sudula M, Kalpana B, Ronnett B, Vijayaraghavan K, Shah K (2010) Effectiveness of VIA, PAP, and HPV DNA testing in a cervical cancer screening program in a peri-urban community in Andhra Pradesh, India. PloS ONE 5(10):e13,711CrossRefGoogle Scholar
  26. Heffernan J, Smith R, Wahl L (2005) Perspectives on the basic reproductive ratio. J R Soc Interface 2(4):281–293CrossRefGoogle Scholar
  27. ICO HPV Information Centre (2017) Human papillomavirus and related cancers, fact sheet. Accessed 14 July 2017
  28. Insinga RP, Dasbach EJ, Elbasha Elamin H, Liaw Kai-Li adn Barr E (2007) Progression and regression of incident cervical HPV 6, 11, 16 and 18 infections in young women. Infect Agents Cancer 2(1):15–25CrossRefGoogle Scholar
  29. Jit M, Gay N, Soldan K, Hong Choi Y, Edmunds WJ (2010) Estimating progression rates for human papillomavirus infection from epidemiological data. Med Decis Mak 30(1):84–98CrossRefGoogle Scholar
  30. Johnson H, Elfström K, Edmunds W (2012) Inference of type-specific HPV transmissibility, progression and clearance rates: a mathematical modelling approach. PLoS ONE 7(11):e49,614CrossRefGoogle Scholar
  31. Kash N, Lee M, Kollipara R, Downing C, Guidry J, Tyring S (2015) Safety and efficacy data on vaccines and immunization to human papillomavirus. J Clin Med 4(4):614–633CrossRefGoogle Scholar
  32. Kim JJ, Salomon JA, Weinstein MC, Goldie SJ (2006) Packaging health services when resources are limited: the example of a cervical cancer screening visit. PLoS Med 3(11):e434CrossRefGoogle Scholar
  33. Labani S, Asthana S, Sodhani P, Gupta S, Bhambhani S, Pooja B, Lim J, Jeronimo J (2014) CareHPV cervical cancer screening demonstration in a rural population of north India. Eur J Obstet Gynecol Reprod Biol 176:75–79CrossRefGoogle Scholar
  34. Lee S, Tameru A (2012) A mathematical model of human papillomavirus (HPV) in the United States and its impact on cervical cancer. J Cancer 3:262–268CrossRefGoogle Scholar
  35. Mandelblatt J, Lawrence W, Womack S, Jacobson D, Yi B, Hwang Y, Gold K, Barter J, Shah K (2002) Benefits and costs of using HPV testing to screen for cervical cancer. J Am Med Assoc 287(18):2372–2381CrossRefGoogle Scholar
  36. Obeng-Denteh W, Afrifa R, Barnes B, Addo K (2014) Modeling the epidemiology of human papilloma virus infection and vaccination and its impact on cervical cancer in Ghana. J Sci Res Rep 3(19):2501–2518Google Scholar
  37. Olsen J (2010) Human papillomavirus transmission and cost-effectiveness of introducing quadrivalent HPV vaccination in denmark. Int J Technol Assess Health Care 26(2):183–191CrossRefGoogle Scholar
  38. Qiagen (2013–2015). Accessed 22 June 2015
  39. Qiao YL, Sellors J, Eder P, Bao YP, Lim J, Zhao FH, Weigl B, Zhang WH, Peck R, Li L, Chen F, Pan QJ, Lorincz A (2008) A new HPV-DNA test for cervical-cancer screening in developing regions: a cross-sectional study of clinical accuracy in rural China. Lancet Oncol 9(10):929–936CrossRefGoogle Scholar
  40. Sanchez M, Blower S (1997) Uncertainty and sensitivity analysis of the basic reproductive rate tuberculosis as an example. Am J Epidemiol 145(12):1127–1137CrossRefGoogle Scholar
  41. Shaban N, Mofi H (2014) Modelling the impact of vaccination and screening on the dynamics of human papillomavirus infection. Int J Math Anal 8(9):441–454MathSciNetCrossRefGoogle Scholar
  42. Shakya S, Syversen U, Åsvold BO, Bofin AM, Aune G, Nordbø SA, Vaidya KM, Karmacharya BM, Afset JE, Tingulstad S (2017) Prevalence of human papillomavirus infection among women in rural Nepal. Acta Obstet Gynecol Scand 96(1):29–38CrossRefGoogle Scholar
  43. Sherpa ATL, Clifford GM, Vaccarella S, Shrestha S, Nygård M, Karki BS, Snijders PJ, Meijer CJ, Franceschi S (2010) Human papillomavirus infection in women with and without cervical cancer in Nepal. Cancer Causes Control 21(3):323–330CrossRefGoogle Scholar
  44. Stoler M, Wright T, Sharma A, Apple R, Gutekunst K, Wright T (2011) The ATHENA HPV Study Group: high-risk human papillomavirus testing in women with ASC-US cytology. Am J Clin Pathol 135(3):468–475CrossRefGoogle Scholar
  45. Szarewski A, Ambroisine L, Cadman L, Austin J, Ho L, Terry G, Liddle S, Dina R, McCarthy J, Buckley H, Bergeron C, Soutter P, Lyons D, Cuzick J (2008) Comparison of predictors for high-grade cervical intraepithelial neoplasia in women with abnormal smears. Cancer Epidemiol Biomark Prev 17(11):3033–3042CrossRefGoogle Scholar
  46. Van den Driessche P, Watmough J (2002) Reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease transmission. Math Biosci 180(1):29–48MathSciNetCrossRefzbMATHGoogle Scholar
  47. World Health Organization (2015) Nepal: WHO statistical profile. Accessed 01 June 2015
  48. World Health Organization (2016) Population fact sheets: world. Accessed 14 June 2016
  49. Wright T Jr, Massad L, Dunton C, Spitzer M, Wilkinson E, Solomon D (2007) 2006 consensus guidelines for the management of women with cervical intraepithelial neoplaisa or adenocarcinoma in situ. Am J Obstet Gynecol 197(4):340–345CrossRefGoogle Scholar
  50. Youens K, Hosler G, Washington P, Jenevein E, Murphy K (2011) Clinical experience with the Cervista HPV HR assay: correlation of cytology and HPV status from 56,501 specimens. J Mol Diagn 13(2):160–166CrossRefGoogle Scholar
  51. Zhai L, Tumban E (2016) Gardasil-9: a global survey of projected efficacy. Antivir Res 130:101–109CrossRefGoogle Scholar

Copyright information

© Society for Mathematical Biology 2018

Authors and Affiliations

  1. 1.Department of Population MedicineUniversity of GuelphGuelphCanada
  2. 2.Department of Mathematics, School of Science, Faculty of Science, Engineering and TechnologySwinburne University of TechnologyMelbourneAustralia
  3. 3.STI UnitInstitut National de Santé Publique du QuébecQuebecCanada
  4. 4.Public Health SchoolUniversité de MontréalMontrealCanada
  5. 5.Centre for Disease Modelling, Department of Mathematics and StatisticsYork UniversityTorontoCanada

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