Health economic evaluation of Human Papillomavirus vaccines in women from Venezuela by a lifetime Markov cohort model

Abstract

Background: Cervical cancer (CC) and genital warts (GW) are a significant public health issue in Venezuela. Our objective was to assess the cost-effectiveness of the two available vaccines, bivalent and quadrivalent, against Human Papillomavirus (HPV) in Venezuelan girls in order to inform decision-makers.

Methods: A previously published Markov cohort model, informed by the best available evidence, was adapted to the Venezuelan context to evaluate the effects of vaccination on health and healthcare costs from the perspective of the healthcare payer in an 11-year-old girls cohort of 264,489. Costs and quality-adjusted life years (QALYs) were discounted at 5%. Eight scenarios were analyzed to depict the cost-effectiveness under alternative vaccine prices, exchange rates and dosing schemes. Deterministic and probabilistic sensitivity analyses were performed.

Results: Compared to screening only, the bivalent and quadrivalent vaccines were cost-saving in all scenarios, avoiding 2,310 and 2,143 deaths, 4,781 and 4,431 CCs up to 18,459 GW for the quadrivalent vaccine and gaining 4,486 and 4,395 discounted QALYs respectively. For both vaccines, the main determinants of variations in the incremental costs-effectiveness ratio after running deterministic and probabilistic sensitivity analyses were transition probabilities, vaccine and cancer-treatment costs and HPV 16 and 18 distribution in CC cases. When comparing vaccines, none of them was consistently more cost-effective than the other. In sensitivity analyses, for these comparisons, the main determinants were GW incidence, the level of cross-protection and, for some scenarios, vaccines costs.

Conclusions: Immunization with the bivalent or quadrivalent HPV vaccines showed to be cost-saving or cost-effective in Venezuela, falling below the threshold of one Gross Domestic Product (GDP) per capita (104,404 VEF) per QALY gained. Deterministic and probabilistic sensitivity analyses confirmed the robustness of these results.

Keywords: Cervical cancer; Genital warts; HPV vaccines; Health economic evaluation; Markov cohort model; Venezuela.

Fig. 1

Model structure. Abbreviations: GCM+: Gardasil-Cervarix Model; CIN1onc, cervical intraepithelial neoplasia 1 oncogenic; CIN1lr, low-risk cervical intraepithelial neoplasia 1; det, CIN health state detected through screening: same pathways as CIN nondetected CIN health state but with different probabilities; HPV, human papillomavirus; HPVlr, low-risk HPV infection; HPVonc, oncogenic HPV infection; NoHPVonc, no oncogenic HPV infection, CIN2/3, cervical intraepithelial neoplasia 2 or 3

Fig. 2

Model calibration. Observed vs. model predicted values. Incidence (a) and mortality (b) of invasive cervical cancer in Venezuela predicted by the model and observed by Globocan and National Health Statistics

Fig. 3

Deterministic Sensitivity Analysis: Tornado graph for QALYs differences. Discount rate = 5%. Abbreviations: T_pob: HPVlr_NoHPV = transition probability to regress from low risk HPV to no HPV; Scenario_Crossprotection = refers to the presence of lifetime cross-protection or no cross-protection at all; T_prob: HPVOnc_NoHPV = Transition probability to regress from infection with oncogenic HPV to no HPV; T_prob: HPVOnc_CIN1 = Transition probability to progress from infection with oncogenic HPV to CIN1; T_prob: CIN1Onc_CIN2/3 = Transition probability to progress from infection with oncogenic HPV and CIN1 to CIN2/3; T_prob: CIN2/3_Cancer = Transition probability to progress from CIN2/3 to cancer; T_prob: CIN1Onc_cured = Transition probability to cure from oncogenic HPV infection with CIN1; T_prob: CIN2/3_Cured = Transition probability to cure from CIN2/3; T_prob: Cancer_Cured = Transition probability to cure from cervical cancer; Vac_efficacy_1618_Cervarix = Vaccine efficacy for oncogenic types with quadrivalent vaccine; Vac_efficacy_1618_Gardasil = Vaccine efficacy for oncogenic types with bivalent vaccine; Vac_eff_other_Gardasil = Vaccine efficacy for non-vaccine oncogenic HPV types with bivalent vaccine; Perc_HPV_6_11 = Proportion of HPV 6 and 11 in genital warts; Perc_other_CC = Proportion of non-vaccine oncogenic HPV types among Cervical Cancer; Perc_HPVOnc = Proportion of HPV 16 and 18 among Cervical Cancer; QALYs: quality-adjusted life years; HPV: Human Papillomavirus

Fig. 4

Deterministic sensitivity analysis – a) Scenario 2 Tornado graph for costs differences in scenario 2 (same vaccine price per dose of 8.5 US$, exchange rate of 6.3 VEF, scheme of 2 doses) b) Scenario 4 Tornado graph for costs differences in scenario 4 (same vaccine price per dose of 8.5 US$, exchange rate of 170 VEF, scheme of 2 doses). Discount rate = 5%. Abbreviations: COSTS_Genital Wart = Costs of genital warts management; COSTS_Cancer = Costs of cervical cancer management; COSTS_Vaccine cervarix = Cost of quadrivalent vaccine; COST_Vaccine Gardasil = Cost of bivalent vaccine; Scenario_Crossprotection = refers to the presence of lifetime cross-protection or no cross-protection at all; T_pob: HPVlr_NoHPV = transition probability to regress from low-risk HPV to no HPV; T_prob: HPVOnc_NoHPV = Transition probability to regress from infection with oncogenic HPV to no HPV; T_prob: HPVOnc_CIN1 = Transition probability to progress from infection with oncogenic HPV to CIN1; T_prob: CIN1Onc_CIN2/3 = Transition probability to progress from infection with oncogenic HPV and CIN1 to CIN2/3; T_prob: CIN2/3_Cancer = Transition probability to progress from CIN2/3 to cancer; T_prob: CIN1Onc_cured = Transition probability to cure from oncogenic HPV infection with CIN1; T_prob: CIN2/3_Cured = Transition probability to cure from CIN2/3; T_prob: Cancer_Cured = Transition probability to cure from cervical cancer; Vac_efficacy_1618_Cervarix = Vaccine efficacy for oncogenic types with quadrivalent vaccine; Vac_efficacy_1618_Gardasil = Vaccine efficacy for oncogenic types with bivalent vaccine; Vac_eff_other_Gardasil = Vaccine efficacy for non-vaccine oncogenic HPV types with bivalent vaccine; Perc_HPV_6_11 = Proportion of HPV 6 and 11 in genital warts; Perc_other_CC = Proportion of non-vaccine oncogenic HPV types among Cervical Cancer; Perc_HPVOnc = Proportion of HPV 16 and 18 among Cervical Cancer; HPV: Human Papillomavirus; VEF: Venezuelan bolívar fuerte; US$: United States dollar

Fig. 5

Probabilistic sensitivity analysis – Scatter plots for a) costs and b) QALYs differences, c) Cost-effectiveness acceptability curves (probability of being the most cost-effective intervention) for scenario 2 (same vaccine price per dose of 8.5 US$, exchange rate of 6.3 VEF, scheme of 2 doses) and scenario 4 (same vaccine price per dose of 8.5 US$, exchange rate of 170 VEF, scheme of 2 doses). Discount rate = 5%. Abbreviations: VEF: Venezuelan bolívar fuerte; US$: United States dollar; GDP: Gross Domestic Product