Background
Methods
Model description
Population
Model input data and assumptions
Natural history related to oncogenic HPV
Natural history-related parameter | Annual probability | |||
---|---|---|---|---|
HIV- subpopulation | Source | HIV+ subpopulation | Source | |
HPV-Onc to CIN1 | 0.049 | Adjusted from [60] (0.15 after 36 months and 0.21 after 60 months) | 0.096 | [49] |
HPV-Onc to CIN2/3 | 0 | Spontaneous progression from HPV-onc to CIN2/3 within 1 year; assumed to be 0 | 0 | Assumption (same as HIV- subpopulation) |
HPV-Onc clearance to normal | 0.293–0.553 | 0.212 | [49] | |
CIN1 to CIN2/3 | 0.091 | 0.098 | [49] | |
CIN2/3 cured | 0.227 | 0.227 | Assumption (same as HIV- subpopulation) | |
CIN2/3 to CIN1 | 0 | Spontaneous regression from CIN2/3 to CIN1 within 1 year; assumed to be 0; all patients cured going to no HPV assumption | 0 | Assumption (same as HIV- subpopulation) |
HIV- CIN2/3 to persistent CIN2/3 | 0.114 | 0.114 | Assumption (same as HIV- subpopulation) | |
Persistent CIN2/3 to cervical cancer | Age 15: 0.00 % | Based on estimated CIN2/3 and reported cervical cancer progression rates | Age 15: 0.00 % | Applied relative risk ratio of 2 for HIV+ based on the progression rate from LSIL to HSIL [64] |
Age 35: 1.10 % | Age 35: 2.20 % | |||
Age 45: 2.52 % | Age 45: 5.04 % | |||
Age 60: 7.56 %a | Age 60: 15.12 %a |
Country specific data
Parameter | Annual probability | |||
---|---|---|---|---|
HIV- subpopulation | Source | HIV+ subpopulation | Source | |
Mortality rate | ||||
General mortality rate | Age 15: 0.09 % | [65] | Age 15: 0.10 % | [65] |
Age 30: 0.20 % | Age 30: 4.62 % | |||
Age 45: 0.51 % | Age 45: 7.71 % | |||
Age 60: 1.56 % | Age 60: 29.72 % | |||
Age 75: 5.31 % | Age 75: 37.38 % | |||
HPV and HIV incidence | ||||
HIV incidence rate in women | NA | - | Age 15: 0.025 | [65] |
Age 30: 0.004 | ||||
Age 45: 0.001 | ||||
Age 60: 0.001 | ||||
65+ years: 0 | ||||
Oncogenic HPV incidence | 0.041–0.390 | [59] | 0.110–1.000 | |
Cervical cancer parameters | ||||
Cervical cancer mortality | 0.110 | [2] | 0.291 | [67] |
Cervical cancer cured | 0.151 | [2] | 0.027 | [67] |
HPV screening-related parameters | ||||
Screening coverage | 13.6 % | [59] | 13.6 % | [59] |
Screening ages | 30–60 years | [63] | 30–60 years | [63] |
Screening frequency | Every 3 years | Every 3 years | ||
CIN1 detected | 0.58 | [68] | 0.58 | [68] |
CIN2/3 detected | 0.61 | [68] | 0.61 | [68] |
HPV-related disease management | ||||
Proportion of women treated if CIN1 is detected | 0.50 | Assumption | 0.50 | Assumption |
CIN1 treatment success | 0.90 | Assumption | 0.90 | Assumption |
Proportion of women treated if CIN2/3 is detected | 1 | Assumption | 1 | Assumption |
CIN2/3 treatment success | 0.90 | Assumption | 0.90 | Assumption |
Cervical cancer screening
Utilities
Health state | Disutility value | Utility value (HIV-); baseline value = 1 | Utility value (HIV+); baseline value = 0.81 |
---|---|---|---|
No HPV | 0 | 1 | 0.81 |
HPV-Onc | 0 | 1 | 0.81 |
CIN1 | 0 | 1 | 0.81 |
CIN1 det | 0.013 | 0.987 | 0.797 |
CIN2/3 | 0 | 1 | 0.81 |
CIN2/3 det | 0.013 | 0.987 | 0.797 |
Cervical cancer | 0.273 | 0.727 | 0.537 |
Cervical cancer cured | 0.062 | 0.938 | 0.748 |
Resource utilisation and disease-related costs
Vaccine costs
Vaccine effectiveness and coverage
Discounting
Data availability
Model outcomes
Base case analysis
Scenario analyses
Sensitivity analysis
-
➢ Overall
-
To account for the uncertainty in model parameters, a one-way sensitivity analysis on the discounted ICER was performed, varying key parameters in the model by ±20 % (x0.8 – x1.2) from their baseline values where 95 % confidence interval (CI) was not available. For vaccine efficacy, the 95 % CI values were taken as minimum and maximum values (see Additional file 3).
-
➢ HIV+ subpopulation
-
Although the vaccine efficacy and duration of protection remains unknown in HIV+ subpopulation, we have evaluated the impact of changes by means of one-way sensitivity analysis on the discounted ICER, by varying the vaccine effectiveness and vaccine duration of protection using the following values:
-
vaccine effectiveness: relative reduction of 5 % (×0.95) to 30 % (×0.70) with a 5 % increment of the base case value
-
vaccine duration of protection: waning of immunity from 5 to 50 years after initial vaccination, followed by a booster dose for 40 % of the cohort at the time of waning.
-
-
➢ Vaccine price
-
A vaccine price sensitivity analysis on the discounted ICER varying the vaccine price with a range of 50 to 150 % of the list price per dose was performed.
Two-way sensitivity analysis
Probabilistic sensitivity analysis
Results
Model validation
Base case analyses
Outcomes | Screening | Screening + HPV vaccination | Incremental value | ICER (ZAR/QALY) |
---|---|---|---|---|
NO DISCOUNTING | ||||
Total costs | ZAR 1 649 427 899 | ZAR 985 679 708 | ZAR −663 748 191 | |
Vaccine cost | ZAR 0 | ZAR 628 612 762 | ZAR 628 612 762 | |
Screening cost | ZAR 149 297 117 | ZAR 153 547 788 | ZAR 4 250 671 | |
CIN1 treatment cost | ZAR 10 577 161 | ZAR 3 746 430 | ZAR −6 830 731 | |
CIN2/3 treatment cost | ZAR 8 262 222 | ZAR 1 813 136 | ZAR −6 449 086 | |
CC treatment cost | ZAR 1 481 291 399 | ZAR 197 959 592 | ZAR −1 283 331 807 | |
Life years | 27 173 430 | 27 230 436 | 57 006 | |
CC cases | 10 244 | 1 376 | −8 869 | |
CC deaths | 6 313 | 877 | −5 436 | |
QALYs | 26 554 764 | 26 623 034 | 68 270 | V + S dominant |
DISCOUNTED AT 5 % | ||||
Total costs | ZAR 221 807 577 | ZAR 692 872 271 | ZAR 471 064 695 | |
Vaccine cost | ZAR 0 | ZAR 628 612 762 | ZAR 628 612 762 | |
Screening cost | ZAR 35 277 421 | ZAR 36 453 101 | ZAR 1 175 681 | |
CIN1 treatment cost | ZAR 2 775 840 | ZAR 1 007 252 | ZAR −1 768 588 | |
CIN2/3 treatment cost | ZAR 2 541 718 | ZAR 553 386 | ZAR −1 988 332 | |
CC treatment cost | ZAR 181 212 598 | ZAR 26 245 770 | ZAR −1 988 332 | |
Life years | 1 283 817 | 9 154 639 | 4 633 | |
QALYs | 8 904 494 | 8 910 240 | 5 746 | ZAR 81 978 |
Scenario analysis
Outcomes | Screening | Screening + HPV vaccination | Incremental value | ICER (ZAR/QALY) |
---|---|---|---|---|
NO DISCOUNTING | ||||
Total costs | ZAR 295 251 951 | ZAR 248 833 762 | ZAR −46 418 189 | |
Vaccine cost | ZAR 0 | ZAR 183 228 152 | ZAR 183 228 152 | |
Screening cost | ZAR 19 794 328 | ZAR 21 262 010 | ZAR 1 467 682 | |
CIN1 treatment cost | ZAR 3 641 306 | ZAR 557 658 | ZAR −3 083 648 | |
CIN2/3 treatment cost | ZAR 3 545 580 | ZAR 561 971 | ZAR −2 983 609 | |
CC treatment cost | ZAR 268 270 736 | ZAR 43 223 970 | ZAR −225 046 766 | |
Life years | 3 179 736 | 3 186 707 | 6 971 | |
CC cases | 2 161 | 348 | −1 813 | |
CC cancer deaths | 2 035 | 328 | −1 707 | |
QALYs | 2 573 677 | 2 580 925 | 7 248 | V + S dominant |
DISCOUNTED AT 5 % | ||||
Total costs | ZAR 62 169 185 | ZAR 198 527 858 | ZAR 136 358 673 | |
Vaccine cost | ZAR 0 | ZAR 183 228 152 | ZAR 183 228 152 | |
Screening cost | ZAR 5 766 054 | ZAR 6 223 334 | ZAR 457 279 | |
CIN1 treatment cost | ZAR 1 126 206 | ZAR 177 452 | ZAR −948 755 | |
CIN2/3 treatment cost | ZAR 1 183 601 | ZAR 190 676 | ZAR −992 925 | |
CC treatment cost | ZAR 54 093 324 | ZAR 8 708 245 | ZAR −45 385 079 | |
Life years | 1 283 817 | 1 285 076 | 1 259 | |
QALYs | 1 039 522 | 1 040 852 | 1 331 | ZAR 102 479 |
Sensitivity analyses
Incidence | HIV+ mortality (base case) | HIV+ mortality −10 % | HIV+ mortality −20 % | HIV+ mortality −30 % | HIV+ mortality −40 % | HIV+ mortality −50 % |
---|---|---|---|---|---|---|
NO DISCOUNTING | ||||||
−75 % | V + S dominant | V + S dominant | V + S dominant | V + S dominant | V + S dominant | V + S dominant |
−50 % | V + S dominant | V + S dominant | V + S dominant | V + S dominant | V + S dominant | V + S dominant |
−25 % | V + S dominant | V + S dominant | V + S dominant | V + S dominant | V + S dominant | V + S dominant |
Base case | V + S dominant | V + S dominant | V + S dominant | V + S dominant | V + S dominant | V + S dominant |
25 % | V + S dominant | V + S dominant | V + S dominant | V + S dominant | V + S dominant | V + S dominant |
50 % | V + S dominant | V + S dominant | V + S dominant | V + S dominant | V + S dominant | V + S dominant |
75 % | V + S dominant | V + S dominant | V + S dominant | V + S dominant | V + S dominant | V + S dominant |
DISCOUNTED AT 5 % | ||||||
−75 % |
85 537
|
84 256
|
82 724
|
80 862
|
78 551
|
75 609
|
−50 % |
83 958
|
81 600
|
78 845
|
75 590
|
71 693
|
66 948
|
−25 % |
82 798
|
79 513
|
75 754
|
71 421
|
66 383
|
60 466
|
Base case |
81 978
|
77 880
|
73 275
|
68 080
|
62 189
|
55 473
|
25 % |
81 435
|
76 610
|
71 279
|
65 375
|
58 824
|
51 540
|
50 % |
81 116
|
75 635
|
69 667
|
63 167
|
56 089
|
48 385
|
75 % |
80 979
|
74 896
|
68 362
|
61 352
|
53 842
|
45 817
|