Table 2

Model natural history parameters, search ranges, and calibrated parameters*
Variables
†
 Before Calibration
 Calibration Results
Parameter Ranges

Parameter Inputs
 Parameter Multiplier
Search Ranges
 Minimum
 Maximum
Progression



From Normal to HPV Infection ‡



     - Low-Risk HPV
 0.1 – 34.5
 1.0 – 4.0
 0.2
 137.3
     - High-Risk HPV-16
 0.1 – 23.4
 1.0 – 8.0 §§
 0.5
 188.6
     - High-Risk HPV-18
 0.0 – 13.8
 1.0 – 8.0 §§
 0.0
 110.1
     - Other High-Risk HPV
 1.2 – 114.5
 1.0 – 8.0
 1.5
 937.3
From HPV Infection to CIN1 §



     - Low-Risk HPV
 55.8 – 64.7
 0.1 – 6.0
 51.7
 377.5
     - High-Risk HPV-16
 57.5 – 102.3
 0.1 – 6.0
 13.2
 621.0
     - High-Risk HPV-18
 57.5 – 102.3
 0.1 – 6.0
 14.8
 595.7
     - Other High-Risk HPV
 57.5 – 102.3
 0.1 – 6.0
 27.3
 615.7
From HPV Infection to CIN2,3 ¶



     - Low-Risk HPV
 0.4 – 9.3
 0.0 – 0.1
 0.0
 0.9
     - High-Risk HPV-16
 2.2 – 46.7
 0.1 – 1.0
 0.3
 46.6
     - High-Risk HPV-18
 2.2 – 46.7
 0.0 – 0.1
 0.0
 4.4
     - Other High-Risk HPV
 2.2 – 46.7
 0.0 – 0.1
 0.0
 4.6
From CIN1 to CIN2,3



     - Low-Risk HPV
 0.4 – 9.3
 0.5 – 4.0
 0.3
 37.0
     - High-Risk HPV-16
 2.2 – 46.7
 0.5 – 6.0
 1.2
 282.4
     - High-Risk HPV-18
 2.2 – 46.7
 0.1 – 4.0
 0.8
 185.1
     - Other High-Risk HPV
 2.2 – 46.7
 0.1 – 4.0
 0.4
 115.1
From CIN2,3 to Local Cancer ||



     - Low-Risk HPV
 0.0
0.0
 0.0
     - High-Risk HPV-16
 0.6 – 72.2
 1.0 – 5.0
 1.1
 362.0
     - High-Risk HPV-18
 0.6 – 72.2
 1.0 – 5.0
 0.8
 362.3
     - Other High-Risk HPV
 0.6 – 72.2
 1.0 – 3.0
 0.7
 216.1
Progression within Cancer



     - Local Cancer to Regional Cancer
 242.4
242.4
 242.4
     - Regional Cancer to Distant Cancer
 303.8
303.8
 303.8
Regression



From CIN2,3 to Normal **



     - Low-Risk HPV
 11.8 – 42.4
 0.5 – 5.0
 6.4
 201.3
     - High-Risk HPV-16
 11.8 – 42.4
 0.5 – 5.0
 6.5
 197.8
     - High-Risk HPV-18
 11.8 – 42.4
 0.5 – 5.0
 6.5
 212.0
     - Other High-Risk HPV
 11.8 – 42.4
 0.5 – 5.0
 6.3
 213.2
From CIN1 to Normal ††



     - Low-Risk HPV
 371.7
 0.5 – 5.0
 229.8
 1968.9
     - High-Risk HPV-16
 371.7
 0.5 – 5.0
 193.2
 1948.8
     - High-Risk HPV-18
 371.7
 0.5 – 5.0 §§
 193.2
 1948.8
     - Other High-Risk HPV
 371.7
 0.5 – 5.0
 310.3
 1974.0
From HPV Infection to Normal ††



     - Low-Risk HPV
 371.7
 1.5 – 6.0
 1,114.2
 2415
     - High-Risk HPV-16
 371.7
 1.5 – 6.0
 589.7
 2324.4
     - High-Risk HPV-18
 371.7
 1.5 – 6.0 §§
 589.7
 2324.4
     - Other High-Risk HPV
 371.7
 1.5 – 6.0
 778.1
 2355.7
Cancer detected by symptoms



     - Local Cancer
 210.6
210.6
 210.6
     - Regional Cancer
 916.1
916.1
 916.1
     - Distant Cancer
 2302.6
2302.6
 2302.6
Mortality



     - All Cause
 0.1 – 297.1
0.1
 297.1
     - Local Cancer
 19.2
19.2
 19.2
     - Regional Cancer
 140.0
140.0
 140.0
     - Distant Cancer
 489.9
489.9
 489.9
Natural Immunity ‡‡



     - Low-Risk HPV
 0%
0%
 0%
     - Other High-Risk HPV
 100%
 0.0 – 1.0
 4%
 90%
     - High-Risk HPV-16
 100%
 0.0 – 1.0 §§
 40%
 99%
     - High-Risk HPV-18
 100%
 0.0 – 1.0 §§
 26%
 100%

* HPV = human papillomavirus; CIN = cervical intraepithelial neoplasia. Values are expressed as yearly rates per 1,000 women, unless otherwise noted.

† Ranges represent age-specific values. Ranges for calibrated values represent the combination multipliers applied to a pre-calibration value or pre-calibration age-specific values, where appropriate.

‡ Multipliers were constrained to be higher for HPV-16 and HPV-18 than for other high-risk HPV.

§ Although pre-calibration rates of progression and the range of multipliers were consistent among all high-risk HPV types, the multipliers were allowed to vary independently by type in the parameter searches.

¶ A proportion of women with HPV transition directly to CIN2,3.

|| Infection with high-risk HPV is considered necessary for progression to invasive cancer

** 70% of women with CIN2,3 clear their infection, 15% retain detectable HPV infection with CIN1, and 15% retain HPV infection without any CIN.

†† Although pre-calibration rates of regression and the range of multipliers were consistent among all HPV types, the multipliers were allowed to vary independently by type in the parameter searches.

‡‡ Immunity represents the percentage reduction in risk of subsequent, type-specific infections after a woman has cleared an infection with the same type. Immunity for HPV-16 and HPV-18 are constrained to be higher than immunity for the category of other high-risk types.

§§ Search range conditional on value randomly drawn for another parameter. Regression rates for HPV-16 and HPV-18 associated CIN1 are assumed to be equal. Clearance rates for HPV-16 and HPV-18 are assumed to be equal. Natural immunity for HPV-16 and HPV-18 are both constrained to be higher than immunity to the category of other high-risk types.

Goldhaber-Fiebert et al. Population Health Metrics 2007 5:11   doi:10.1186/1478-7954-5-11