Supplementary Material for:

(1)

1 Supplementary Material for:

Choosing wisely: A model-based analysis evaluating the trade-offs in cancer benefit and diagnostic referrals among alternative HPV testing strategies in Norway

Authors:

Emily A. Burger*

Kine Pedersen*

Stephen Sy

Ivar Sonbo Kristiansen Jane J. Kim

*Denotes equal contribution Corresponding author:

Emily A. Burger

Harvard T.H. Chan School of Public Health Center for Health Decision Science

718 Huntington Avenue, 2nd Floor Boston, MA, 02115 USA

eburger@hsph.harvard.edu

CONTENTS:

1. Model validation results

2. Supplementary results from base-case analysis 3. Supplementary results from uncertainty analysis

(2)

2 1. Model validation results

Under current patterns of screening behaviour in Norway (Norwegian Technical Appendix, 2017) the model projects an average of 10,664 colposcopy/biopsies (uncertainty bound (UB): 8,964- 11,655), which overlapped with the colposcopy/biopsy rates (i.e. 11,331-11,943) reported between 2008-2012 by the Cancer Registry of Norway (Cancer Registry of Norway, 2013; 2014;

2015) (Supplementary Figure 1).

Supplementary Figure 1. Model validation of colposcopy/biopsy referral rates.

2. Supplementary results from primary analysis

Under assumptions of perfect screening adherence, the minimum and maximum values across 50 parameter sets (i.e. representing the uncertainty bounds) for the primary analysis outcomes (i.e. the reduction in cervical cancer incidence compared to no screening, the relative number of colposcopy referral rates compared to current guidelines, and the number of colposcopy

referrals per cancer prevented compared to no screening) are presented in Supplementary Figures 2-7. Additional results for health benefit outcomes, including the reduction in cervical cancer incidence for alternative HPV-based strategies compared to current guidelines and the number of women who developed cervical cancer per 1,000 women screened over a lifetime, are presented in Supplementary Figures 8 and 9. Additional results for resource outcomes are presented in Supplementary Figures 10-13. For alternative primary HPV-based strategies and per 1,000 women screened over their lifetime, the total number of cytology and HPV tests ranged from 10,005 (UB: 9,434-10,507) to 26,912 (UB: 25,083-28,179) tests (Supplementary Figure 10), the number of colposcopy referrals ranged from 605 (UB: 511-662) to 2,441 (UB:

2,055-2,681) referrals (Supplementary Figure 11), and the number of precancer treatments ranged from 211 (UB: 161-240) to 444 (UB: 354-498) treatments (Supplementary Figure 12).

In comparison, we projected the current Norwegian cytology-based guidelines would require 17,958 (UB: 17,688-18,131) screening tests, 567 (483-618) colposcopy referrals, and 197 (148- 223) precancer treatments, per 1,000 women screened.Finally, the additional number of colposcopies required to prevent one additional cervical cancer compared to the current Norwegian guidelines ranged from 38 (11-76) to 735 (637-969) (Supplementary Figure 13).

(3)

3 3. Supplementary results from uncertainty analysis

The reduction in cancer incidence of alternative HPV-based strategies compared to no screening was most influenced by reducing the HPV test sensitivity (given the presence of a high-risk HPV infection) to 90%. In this scenario, lifetime cancer risk reductions ranged from 84.2% (UB: 82.6-85.2%) to 94.6% (94.1-95.2%) for alternative primary HPV-based strategies compared to no screening (Supplementary Figure 14). Compared to the base-case analysis, the primary screening frequency is now more influential in reducing cancer risk than switching age. Of note, the implied screening stop age of routine screening varies by assumptions around screening frequency in combination with switching age; slight inconsistencies in cancer risk reductions due to screening stopping age become more apparent with lower HPV sensitivity. In contrast, assuming perfect diagnostic accuracy of a colposcopy-directed biopsy had nominal impact on cancer risk reductions, ranging from 91.6% (UB: 90.7-92.7%) to 96.6% (UB: 96.2- 97.1%) (Supplementary Figure 15).

The impact of HPV-based strategies on colposcopy referral rates was most influenced by the baseline comparator strategy. For example, when we calculated relative colposcopy rates using the current triennial cytology-based guidelines recommended in the US as a baseline strategy, approximately two-thirds of the HPV-based strategy algorithms we considered were expected to increase colposcopy referrals (Supplementary Figure 18). When using current guidelines in Norway as a baseline comparator strategy, we found colposcopy referral rates to moderately decrease when assuming an HPV test sensitivity of 90% (Supplementary Figure 16), and to moderately increase when assuming perfect diagnostic accuracy of a colposcopy-directed biopsy (Supplementary Figure 17).

Finally, the number of colposcopy referrals per cancer prevented across algorithms was reduced when assuming an HPV test sensitivity of 90% (Supplementary Figure 19), and increased when assuming perfect colposcopy characteristics (Supplementary Figure 20).

(4)

4 Supplementary Figure 2. The reduction in cervical cancer incidence (compared to no screening): The minimum value across the 50 parameter sets for the base-case analysis.

The corresponding value for the current Norwegian guidelines was 86.6%.

3 4 5 6 8 10 3 4 5 6 8 10

95.8 % 95.5 % 95.6 % 95.3 % 94.7 % 94.4 % 1 94.3 % 94.2 % 94.1 % 94.0 % 93.7 % 93.4 % 95.8 % 95.6 % 95.5 % 95.2 % 94.7 % 94.4 % 2 94.3 % 94.2 % 94.0 % 94.0 % 93.5 % 93.1 % 95.7 % 95.6 % 95.4 % 95.3 % 94.6 % 94.4 % 3 94.2 % 94.2 % 94.0 % 94.0 % 93.6 % 93.1 % 95.5 % 95.4 % 95.2 % 95.1 % 94.6 % 94.1 % 1 94.2 % 94.0 % 93.8 % 93.7 % 93.3 % 92.9 % 95.5 % 95.4 % 95.2 % 95.0 % 94.4 % 93.9 % 2 94.1 % 93.9 % 93.7 % 93.6 % 93.3 % 92.9 % 95.3 % 95.2 % 95.0 % 94.9 % 94.3 % 93.7 % 3 94.0 % 93.8 % 93.6 % 93.5 % 93.2 % 92.7 % 95.4 % 95.3 % 95.1 % 95.1 % 94.4 % 93.9 % 1 94.1 % 93.8 % 93.7 % 93.6 % 93.2 % 92.7 % 95.1 % 94.9 % 94.7 % 94.6 % 94.0 % 93.3 % 2 93.8 % 93.5 % 93.4 % 93.3 % 92.9 % 92.3 % 94.9 % 94.6 % 94.5 % 94.3 % 93.7 % 92.9 % 3 93.6 % 93.3 % 93.2 % 93.1 % 92.6 % 92.0 % 93.2 % 93.0 % 92.8 % 92.8 % 91.9 % 91.0 % 1 92.3 % 92.3 % 92.0 % 92.0 % 91.5 % 90.9 % 93.1 % 92.9 % 92.7 % 92.7 % 91.8 % 90.8 % 2 92.2 % 92.2 % 92.1 % 92.0 % 91.4 % 90.8 % 93.0 % 92.8 % 92.6 % 92.7 % 91.7 % 90.8 % 3 92.2 % 92.2 % 92.1 % 91.9 % 91.4 % 90.8 % 93.1 % 92.9 % 92.6 % 92.6 % 91.7 % 90.7 % 1 92.2 % 92.1 % 92.0 % 91.8 % 91.4 % 90.9 % 93.0 % 92.7 % 92.5 % 92.4 % 91.5 % 90.5 % 2 92.1 % 92.0 % 91.9 % 91.8 % 91.4 % 90.8 % 92.8 % 92.6 % 92.4 % 92.4 % 91.4 % 90.4 % 3 92.0 % 91.9 % 91.8 % 91.7 % 91.3 % 90.6 % 93.0 % 92.7 % 92.4 % 92.6 % 91.6 % 90.6 % 1 92.1 % 92.0 % 91.8 % 91.7 % 91.3 % 90.7 % 92.8 % 92.5 % 92.2 % 92.3 % 91.3 % 90.2 % 2 91.9 % 91.8 % 91.6 % 91.5 % 91.0 % 90.3 % 92.7 % 92.3 % 92.1 % 92.2 % 91.0 % 90.0 % 3 91.8 % 91.7 % 91.6 % 91.4 % 90.9 % 90.1 %

6

Wait time (months)

12 12

18 18

Switch age 31 Switch age 34

6 6

12 12

18 18

Reduction in cancer incidence (compared to no screening) Screening frequency (years) Number

repeat visits

Screening frequency (years)

6

(5)

5 Supplementary Figure 3. The reduction in cervical cancer incidence (compared to no screening): The maximum value across the 50 parameter sets for the base-case analysis.

3 4 5 6 8 10 3 4 5 6 8 10

96.8 % 96.6 % 96.6 % 96.4 % 96.0 % 95.5 % 1 95.9 % 95.8 % 95.7 % 95.6 % 95.4 % 95.0 % 96.8 % 96.7 % 96.6 % 96.4 % 95.9 % 95.5 % 2 95.9 % 95.7 % 95.7 % 95.6 % 95.1 % 94.8 % 96.8 % 96.6 % 96.6 % 96.3 % 95.9 % 95.5 % 3 95.8 % 95.7 % 95.5 % 95.5 % 95.2 % 94.8 % 96.7 % 96.6 % 96.5 % 96.2 % 95.8 % 95.3 % 1 95.8 % 95.6 % 95.5 % 95.4 % 95.0 % 94.6 % 96.6 % 96.4 % 96.3 % 96.0 % 95.7 % 95.1 % 2 95.7 % 95.6 % 95.4 % 95.3 % 95.0 % 94.6 % 96.5 % 96.3 % 96.2 % 96.0 % 95.6 % 94.9 % 3 95.6 % 95.4 % 95.3 % 95.2 % 94.9 % 94.4 % 96.6 % 96.5 % 96.4 % 96.2 % 95.8 % 95.1 % 1 95.6 % 95.5 % 95.4 % 95.3 % 95.0 % 94.4 % 96.4 % 96.2 % 96.1 % 95.8 % 95.5 % 94.7 % 2 95.5 % 95.3 % 95.1 % 95.1 % 94.7 % 94.2 % 96.1 % 96.0 % 95.9 % 95.7 % 95.2 % 94.4 % 3 95.2 % 95.1 % 94.9 % 94.9 % 94.4 % 93.9 % 95.0 % 94.7 % 94.6 % 94.5 % 93.7 % 93.0 % 1 94.1 % 94.1 % 93.9 % 93.9 % 93.4 % 92.9 % 95.0 % 94.7 % 94.5 % 94.5 % 93.7 % 92.9 % 2 94.1 % 94.0 % 93.9 % 93.8 % 93.4 % 92.9 % 94.9 % 94.6 % 94.4 % 94.5 % 93.6 % 92.8 % 3 94.1 % 94.0 % 93.9 % 93.8 % 93.4 % 92.8 % 94.9 % 94.7 % 94.5 % 94.4 % 93.7 % 92.8 % 1 94.1 % 93.9 % 93.8 % 93.7 % 93.3 % 92.8 % 94.7 % 94.5 % 94.4 % 94.3 % 93.5 % 92.7 % 2 93.9 % 93.9 % 93.7 % 93.6 % 93.3 % 92.7 % 94.7 % 94.4 % 94.2 % 94.1 % 93.4 % 92.6 % 3 93.8 % 93.8 % 93.7 % 93.6 % 93.2 % 92.6 % 94.7 % 94.5 % 94.2 % 94.3 % 93.5 % 92.6 % 1 93.9 % 93.8 % 93.6 % 93.6 % 93.3 % 92.7 % 94.7 % 94.4 % 94.2 % 94.2 % 93.4 % 92.5 % 2 93.8 % 93.6 % 93.5 % 93.4 % 93.0 % 92.3 % 94.4 % 94.2 % 94.0 % 93.9 % 93.1 % 92.1 % 3 93.6 % 93.5 % 93.3 % 93.2 % 92.8 % 92.1 %

6

12 12

18 18

6 6

12 12

18 18

6

(6)

6 Supplementary Figure 4. Relative colposcopy referral rates (compared to current guidelines): The minimum value across the 50 parameter sets for the base-case analysis.

3 4 5 6 8 10 3 4 5 6 8 10

4.12 3.63 3.29 3.01 2.62 2.36 1 3.58 3.16 2.86 2.64 2.30 2.07

3.44 3.06 2.80 2.57 2.25 2.04 2 3.02 2.68 2.44 2.27 1.99 1.80

3.02 2.71 2.48 2.29 2.02 1.83 3 2.66 2.39 2.19 2.04 1.80 1.64

3.40 3.03 2.76 2.55 2.24 2.02 1 2.98 2.65 2.42 2.24 1.97 1.79

2.59 2.35 2.16 2.00 1.78 1.61 2 2.30 2.09 1.92 1.80 1.61 1.46

2.18 1.99 1.84 1.72 1.52 1.39 3 1.96 1.79 1.66 1.56 1.40 1.28

2.93 2.64 2.42 2.25 1.98 1.79 1 2.58 2.32 2.13 1.98 1.76 1.60

2.12 1.93 1.79 1.67 1.48 1.35 2 1.90 1.74 1.62 1.53 1.36 1.25

1.76 1.61 1.50 1.41 1.26 1.15 3 1.61 1.48 1.38 1.31 1.18 1.09

3.20 2.82 2.54 2.36 2.03 1.81 1 2.90 2.59 2.35 2.18 1.90 1.71

2.71 2.41 2.19 2.05 1.78 1.60 2 2.47 2.23 2.04 1.90 1.68 1.53

2.41 2.16 1.98 1.85 1.62 1.46 3 2.21 2.01 1.85 1.73 1.55 1.41

2.68 2.39 2.17 2.03 1.76 1.59 1 2.44 2.20 2.02 1.88 1.67 1.52

2.10 1.90 1.76 1.65 1.46 1.32 2 1.94 1.78 1.65 1.55 1.40 1.28

1.80 1.65 1.54 1.46 1.29 1.18 3 1.68 1.56 1.46 1.38 1.25 1.15

2.33 2.10 1.93 1.81 1.59 1.43 1 2.14 1.95 1.81 1.69 1.51 1.38

1.76 1.61 1.50 1.42 1.26 1.15 2 1.64 1.52 1.43 1.35 1.22 1.13

1.51 1.39 1.30 1.24 1.11 1.03 3 1.43 1.33 1.25 1.19 1.10 1.02

12 12

18 18

6 6

12 12

18 18

Relative colposcopy referral rates (compared to current guidelines) Screening frequency (years) Number

6 6

(7)

7 Supplementary Figure 5. Relative colposcopy referral rates (compared to current guidelines): The maximum value across the 50 parameter sets for the base-case analysis.

3 4 5 6 8 10 3 4 5 6 8 10

4.51 3.99 3.62 3.31 2.88 2.60 1 3.95 3.49 3.17 2.92 2.54 2.29

3.80 3.39 3.09 2.84 2.48 2.24 2 3.34 2.98 2.72 2.52 2.20 1.99

3.34 3.00 2.75 2.54 2.23 2.02 3 2.96 2.65 2.44 2.26 2.00 1.81

3.76 3.36 3.06 2.82 2.48 2.24 1 3.30 2.95 2.69 2.49 2.19 1.98

2.88 2.61 2.40 2.23 1.98 1.80 2 2.57 2.33 2.15 2.00 1.78 1.62

2.42 2.21 2.04 1.91 1.70 1.55 3 2.18 1.99 1.85 1.73 1.56 1.43

3.26 2.94 2.69 2.50 2.20 2.00 1 2.88 2.59 2.38 2.21 1.96 1.78

2.36 2.16 2.00 1.87 1.67 1.53 2 2.12 1.94 1.80 1.70 1.52 1.40

1.96 1.80 1.68 1.57 1.42 1.31 3 1.79 1.64 1.54 1.45 1.32 1.22

3.53 3.11 2.81 2.61 2.24 1.99 1 3.19 2.85 2.58 2.39 2.09 1.88

3.00 2.68 2.43 2.27 1.96 1.76 2 2.73 2.46 2.25 2.10 1.85 1.68

2.67 2.40 2.19 2.05 1.79 1.61 3 2.44 2.21 2.04 1.91 1.69 1.54

2.97 2.65 2.42 2.25 1.95 1.75 1 2.70 2.43 2.24 2.07 1.84 1.66

2.33 2.11 1.95 1.83 1.61 1.46 2 2.14 1.96 1.82 1.71 1.54 1.41

2.00 1.83 1.70 1.61 1.43 1.30 3 1.85 1.71 1.60 1.51 1.37 1.26

2.60 2.34 2.15 2.01 1.76 1.59 1 2.38 2.16 2.00 1.86 1.67 1.52

1.95 1.79 1.66 1.57 1.40 1.28 2 1.81 1.68 1.57 1.48 1.35 1.24

1.66 1.53 1.43 1.37 1.23 1.14 3 1.56 1.46 1.38 1.31 1.20 1.12

6

12 12

18 18

6 6

12 12

18 18

Relative colposcopy referral rates (compared to current guidelines) Screening frequency (years) Number

6

(8)

8 Supplementary Figure 6 The number of colposcopy referrals per cancer prevented (compared to no screening): The minimum value across the 50 parameter sets for the base-case analysis.

The corresponding value for the current Norwegian guidelines was 18.1.

3 4 5 6 8 10 3 4 5 6 8 10

69.6 61.6 55.9 51.2 44.5 40.2 1 61.4 54.2 49.1 45.2 39.4 35.5

58.3 52.0 47.4 43.6 38.2 34.7 2 51.8 46.0 42.0 38.9 34.1 30.9

51.2 46.0 42.0 38.9 34.3 31.1 3 45.7 41.0 37.6 34.9 30.8 28.1

57.7 51.6 47.0 43.3 38.1 34.5 1 51.1 45.7 41.6 38.5 33.9 30.7

44.0 39.8 36.6 34.0 30.2 27.7 2 39.6 35.9 33.0 30.8 27.5 25.2

37.0 33.6 31.1 29.1 26.1 24.0 3 33.6 30.7 28.5 26.8 24.1 22.2

49.8 44.9 41.1 38.1 33.7 30.7 1 44.4 40.0 36.7 34.1 30.3 27.6

35.9 32.8 30.4 28.4 25.5 23.5 2 32.7 29.9 27.8 26.2 23.6 21.8

29.7 27.4 25.5 24.1 21.8 20.2 3 27.5 25.4 23.8 22.6 20.6 19.2

55.5 49.0 44.2 40.9 35.4 31.7 1 50.6 45.2 41.0 38.0 33.3 30.1

47.1 42.0 38.2 35.6 31.1 28.0 2 43.2 38.9 35.7 33.2 29.5 26.8

41.8 37.5 34.4 32.1 28.3 25.7 3 38.6 35.0 32.3 30.2 27.0 24.7

46.5 41.5 37.9 35.3 30.8 27.9 1 42.7 38.5 35.4 32.8 29.2 26.6

36.4 33.0 30.5 28.6 25.5 23.3 2 33.9 31.0 28.8 27.1 24.4 22.6

31.2 28.6 26.6 25.2 22.6 20.9 3 29.3 27.1 25.4 24.0 22.0 20.4

40.6 36.6 33.6 31.4 27.7 25.3 1 37.5 34.1 31.6 29.5 26.4 24.3

30.5 27.9 26.0 24.6 22.2 20.5 2 28.6 26.5 24.9 23.6 21.5 20.1

26.0 24.1 22.6 21.5 19.7 18.3 3 24.7 23.1 21.9 20.9 19.4 18.2

6

12 12

18 18

6 6

12 12

18 18

Number of colposcopy referrals per cancer prevented (compared to no screening) Screening frequency (years) Number

6

(9)

9 Supplementary Figure 7. The number of colposcopy referrals per cancer prevented (compared to no screening): The maximum value across the 50 parameter sets for the base-case analysis.

3 4 5 6 8 10 3 4 5 6 8 10

121.9 108.2 98.8 90.8 79.6 72.4 1 107.4 95.4 86.7 80.4 70.7 64.1

102.6 91.8 84.3 78.0 68.8 62.8 2 91.0 81.4 74.6 69.6 61.7 56.3

90.5 81.7 75.3 69.9 62.2 56.8 3 80.7 72.8 67.1 62.7 56.0 51.4

101.7 91.2 83.6 77.5 68.7 62.7 1 90.0 80.7 74.0 69.0 61.2 56.0

78.4 71.3 66.0 61.7 55.1 50.8 2 70.3 64.1 59.4 55.8 50.3 46.4

66.4 60.8 56.6 53.2 48.0 44.3 3 60.2 55.3 51.7 48.7 44.3 41.1

88.3 79.9 73.6 68.7 61.2 56.1 1 78.6 71.1 65.7 61.5 55.0 50.6

64.5 59.3 55.4 52.1 46.9 43.5 2 58.6 53.9 50.4 47.7 43.4 40.3

54.1 50.0 46.9 44.3 40.3 37.6 3 49.9 46.2 43.5 41.4 37.9 35.5

96.8 85.7 77.9 72.4 63.2 57.2 1 88.1 79.0 71.9 67.1 59.2 53.8

82.5 73.9 67.6 63.4 55.9 50.8 2 75.5 68.5 63.0 59.0 52.6 48.2

73.5 66.4 61.2 57.5 51.1 46.7 3 67.6 61.7 57.2 53.8 48.4 44.6

81.5 73.1 67.1 62.9 55.5 50.5 1 74.6 67.5 62.4 58.4 52.2 47.8

64.4 58.8 54.6 51.5 46.2 42.6 2 59.7 54.9 51.4 48.5 44.0 40.9

55.8 51.3 48.0 45.6 41.3 38.3 3 52.1 48.4 45.6 43.3 39.7 37.1

71.5 64.8 59.9 56.4 50.2 46.1 1 65.8 60.1 56.0 52.6 47.4 43.8

54.3 50.1 47.0 44.7 40.6 37.7 2 50.9 47.4 44.7 42.5 39.0 36.5

46.8 43.4 41.0 39.2 35.9 33.6 3 44.3 41.6 39.5 37.8 35.1 33.0

Number repeat

visits

6 6

12 12

18 18

6 6

12 12

18 18

Number of colposcopy referrals per cancer prevented (compared to no screening) Screening frequency (years)

(10)

10 Supplementary Figure 8. The reduction in cervical cancer incidence (compared to current cytology-based guidelines in Norway):

The average value across the 50 parameter sets for the base-case analysis.

3 4 5 6 8 10 3 4 5 6 8 10

69.7 % 68.2 % 67.7 % 66.3 % 62.4 % 59.2 % 1 59.5 % 58.5 % 57.5 % 56.8 % 54.6 % 52.0 % 69.3 % 68.6 % 67.7 % 66.1 % 62.1 % 59.1 % 2 58.6 % 57.8 % 56.9 % 56.5 % 53.1 % 50.2 % 68.6 % 68.1 % 67.2 % 65.4 % 61.5 % 58.9 % 3 58.4 % 57.6 % 56.6 % 56.2 % 53.4 % 50.2 % 68.0 % 67.1 % 65.7 % 64.8 % 60.6 % 57.2 % 1 58.0 % 56.6 % 55.3 % 54.5 % 51.7 % 48.4 % 67.3 % 66.3 % 64.6 % 63.4 % 59.4 % 55.5 % 2 56.8 % 55.7 % 54.6 % 53.4 % 51.1 % 48.0 % 66.2 % 65.1 % 63.4 % 62.6 % 58.3 % 53.9 % 3 56.3 % 54.9 % 53.6 % 52.7 % 50.3 % 47.0 % 67.2 % 66.3 % 64.7 % 63.9 % 59.8 % 55.7 % 1 56.7 % 54.8 % 53.9 % 53.2 % 50.2 % 46.4 % 64.6 % 63.1 % 61.9 % 60.9 % 56.6 % 51.5 % 2 54.7 % 52.8 % 51.6 % 51.0 % 47.8 % 43.5 % 62.4 % 61.0 % 59.6 % 58.9 % 53.9 % 48.3 % 3 52.8 % 51.3 % 49.9 % 49.2 % 45.7 % 41.3 % 50.0 % 48.1 % 46.5 % 46.8 % 39.3 % 33.2 % 1 42.6 % 42.4 % 40.8 % 40.5 % 36.9 % 32.5 % 49.5 % 48.0 % 46.2 % 46.5 % 39.2 % 33.0 % 2 42.3 % 41.9 % 41.0 % 40.1 % 36.1 % 31.9 % 49.1 % 47.2 % 45.7 % 46.1 % 38.8 % 32.4 % 3 42.3 % 42.0 % 41.1 % 40.1 % 36.4 % 31.7 % 49.0 % 47.3 % 45.2 % 45.4 % 38.8 % 32.0 % 1 42.2 % 41.3 % 40.2 % 39.1 % 35.9 % 31.9 % 48.1 % 46.1 % 44.6 % 44.4 % 37.3 % 30.8 % 2 41.3 % 40.7 % 39.5 % 38.3 % 35.6 % 30.8 % 47.3 % 45.5 % 43.8 % 43.7 % 36.5 % 29.9 % 3 40.9 % 40.0 % 39.1 % 37.8 % 34.8 % 30.1 % 48.2 % 46.3 % 43.9 % 44.6 % 37.5 % 30.5 % 1 41.4 % 40.3 % 39.2 % 37.9 % 35.2 % 30.3 % 46.8 % 44.6 % 42.7 % 43.1 % 35.5 % 28.3 % 2 40.1 % 38.6 % 37.7 % 36.5 % 32.9 % 28.0 % 45.3 % 42.9 % 41.5 % 41.2 % 33.5 % 26.0 % 3 39.4 % 38.1 % 37.0 % 35.8 % 31.8 % 26.8 %

Switch age 34

18 18

6

12 Switch age 31

Reduction in cancer incidence (compared to current guidelines)

Number repeat

visits

18 18

6

12 6

12

6

12

(11)

11 Supplementary Figure 9. The total number of women who developed cervical cancer per 1,000 women screened over a lifetime:

The average value across the 50 parameter sets for the base-case analysis.

3 4 5 6 8 10 3 4 5 6 8 10

1.19 1.24 1.26 1.33 1.49 1.61 1 1.54 1.58 1.62 1.65 1.74 1.83

1.20 1.23 1.26 1.33 1.50 1.61 2 1.57 1.60 1.64 1.66 1.80 1.90

1.22 1.25 1.28 1.35 1.52 1.62 3 1.58 1.61 1.65 1.67 1.78 1.90

1.25 1.28 1.34 1.38 1.54 1.67 1 1.59 1.65 1.70 1.73 1.85 1.97

1.27 1.31 1.37 1.43 1.59 1.73 2 1.63 1.67 1.72 1.77 1.86 1.97

1.30 1.35 1.41 1.45 1.63 1.79 3 1.65 1.70 1.75 1.79 1.89 2.01

1.27 1.30 1.37 1.40 1.58 1.72 1 1.63 1.71 1.74 1.78 1.89 2.03

1.36 1.41 1.46 1.51 1.68 1.87 2 1.70 1.78 1.83 1.85 1.98 2.13

1.44 1.48 1.54 1.58 1.78 1.98 3 1.77 1.83 1.89 1.91 2.05 2.21

1.87 1.95 2.01 2.01 2.32 2.57 1 2.13 2.14 2.20 2.22 2.37 2.56

1.89 1.96 2.03 2.02 2.33 2.58 2 2.14 2.16 2.20 2.23 2.39 2.57

1.90 1.98 2.05 2.03 2.34 2.60 3 2.14 2.16 2.19 2.23 2.38 2.58

1.91 1.98 2.06 2.05 2.34 2.62 1 2.15 2.18 2.22 2.27 2.40 2.58

1.94 2.02 2.08 2.09 2.39 2.65 2 2.18 2.21 2.25 2.30 2.42 2.62

1.97 2.04 2.12 2.11 2.42 2.69 3 2.19 2.23 2.26 2.32 2.44 2.64

1.93 2.01 2.11 2.08 2.38 2.66 1 2.17 2.22 2.25 2.31 2.43 2.63

1.98 2.07 2.15 2.13 2.45 2.74 2 2.22 2.27 2.30 2.36 2.50 2.71

2.03 2.13 2.19 2.20 2.52 2.82 3 2.24 2.30 2.33 2.39 2.54 2.75

Total number of women with cancer per 1,000 women Screening frequency (years) Number

6 6

12 12

18 18

6 6

12 12

18 18

(12)

12 Supplementary Figure 10. The total number of screening tests (i.e. cytology and HPV tests) per 1,000 women screened over a lifetime: The average value across the 50 parameter sets for the base-case analysis.

The corresponding value for the current Norwegian guidelines was 17,958 per 1,000 women screened over a lifetime.

3 4 5 6 8 10 3 4 5 6 8 10

26912 22136 19180 16877 13890 12096 1 25362 20992 18228 16303 13649 11980 27258 22474 19422 17124 14081 12264 2 25653 21167 18377 16483 13742 12061 27523 22746 19641 17329 14259 12420 3 25880 21401 18590 16644 13911 12212 24904 20533 17657 15612 12845 11177 1 23640 19550 16960 15150 12691 11142 24274 19998 17195 15186 12501 10878 2 23109 19154 16621 14813 12469 10960 23992 19749 16984 15027 12357 10749 3 22879 18946 16451 14657 12347 10857 23581 19454 16690 14773 12136 10560 1 22531 18590 16138 14421 12104 10638 22545 18546 15900 14064 11541 10041 2 21666 17867 15498 13866 11641 10240 22113 18167 15563 13772 11288 9814 3 21313 17568 15230 13633 11446 10071 24238 20090 17478 15839 13107 11482 1 23352 19817 17390 15879 13570 12091 24490 20302 17643 16019 13244 11600 2 23567 19975 17600 16014 13679 12192 24684 20476 17808 16169 13363 11699 3 23734 20129 17760 16132 13786 12283 22736 18906 16462 14942 12394 10881 1 22028 18683 16543 15002 12919 11546 22277 18524 16149 14644 12169 10695 2 21622 18354 16256 14756 12725 11381 22082 18368 15994 14538 12069 10610 3 21455 18193 16123 14643 12628 11303 21785 18128 15756 14346 11904 10467 1 21206 17966 15964 14462 12474 11173 21048 17497 15227 13862 11523 10147 2 20562 17436 15501 14058 12135 10889 20745 17233 15023 13658 11355 10005 3 20304 17231 15311 13892 12013 10774

12 12

18 18

6 6

12 12

18 18

Total number of lifetime screening tests (i.e. cytology and HPV tests) per 1,000 women Screening frequency (years) Number

6 6

(13)

13 Supplementary Figure 11. The total number of colposcopy referrals per 1,000 women screened over a lifetime: The average value across the 50 parameter sets for the base-case analysis.

The corresponding value for the current Norwegian guidelines was 567 per 1,000 women screened over a lifetime.

3 4 5 6 8 10 3 4 5 6 8 10

2441 2155 1956 1788 1551 1396 1 2130 1881 1703 1567 1365 1227

2047 1824 1662 1529 1334 1205 2 1797 1598 1457 1350 1182 1068

1798 1614 1477 1363 1197 1083 3 1588 1423 1304 1212 1069 971

2025 1808 1646 1518 1328 1200 1 1775 1583 1443 1335 1172 1059

1547 1400 1286 1193 1056 961 2 1373 1245 1146 1068 953 869

1300 1183 1094 1022 911 831 3 1167 1066 989 927 834 766

1751 1578 1442 1338 1177 1068 1 1543 1387 1272 1182 1047 951

1263 1153 1067 998 889 814 2 1136 1037 963 906 815 748

1045 961 894 842 756 695 3 956 880 823 779 707 654

1902 1676 1512 1401 1201 1069 1 1721 1535 1391 1289 1127 1012

1615 1437 1305 1218 1054 944 2 1470 1323 1212 1127 995 900

1434 1285 1176 1101 960 864 3 1311 1191 1097 1025 912 830

1594 1421 1295 1208 1047 939 1 1451 1307 1201 1114 988 894

1248 1131 1043 980 863 784 2 1150 1053 978 917 826 756

1072 979 910 861 766 700 3 996 920 861 814 740 683

1393 1254 1149 1077 942 850 1 1276 1159 1073 1000 894 815

1045 957 889 843 751 687 2 973 900 845 798 726 671

891 822 771 734 662 610 3 840 785 742 706 649 605

6

12 12

18 18

6 6

12 12

18 18

Total number of colposcopy referrals per 1,000 women Screening frequency (years) Number

6

(14)

14 Supplementary Figure 12. The total number of precancer treatments per 1,000 women screened over a lifetime: The average value across the 50 parameter sets for the base-case analysis.

The corresponding value for the current Norwegian guidelines was 197 per 1,000 women screened over a lifetime.

3 4 5 6 8 10 3 4 5 6 8 10

444 412 390 369 336 311 1 402 374 353 337 309 287

405 379 361 344 315 293 2 369 346 329 316 292 271

381 360 343 328 302 282 3 349 329 315 303 281 263

400 375 356 340 312 290 1 364 342 325 312 288 269

352 334 320 307 284 266 2 324 308 296 285 266 250

328 313 301 290 270 253 3 304 291 281 271 255 240

370 350 333 319 294 274 1 339 320 306 294 274 256

320 305 293 283 263 246 2 297 284 274 265 249 234

297 285 275 266 248 233 3 278 267 259 252 237 224

371 345 326 313 284 262 1 347 327 309 298 274 256

343 322 305 295 270 250 2 322 306 292 282 262 245

325 307 293 284 261 243 3 307 293 282 272 254 239

339 318 303 292 267 248 1 319 302 289 278 259 243

304 289 278 269 249 232 2 289 277 268 259 243 229

287 275 265 258 239 224 3 274 264 256 248 235 222

317 300 287 278 255 237 1 300 286 276 265 249 234

281 269 259 253 235 220 2 269 259 252 244 231 218

265 255 247 241 225 212 3 255 247 241 234 222 211

6

12 12

18 18

6 6

12 12

18 18

Total number of precancer treatments per 1,000 women Screening frequency (years) Number

6

(15)

15 Supplementary Figure 13. The additional number of colposcopy referrals per additional cervical cancer prevented (compared to current Norwegian guidelines): The average value across the 50 parameter sets for the base-case analysis.

3 4 5 6 8 10 3 4 5 6 8 10

735 637 561 507 438 389 1 710 607 534 478 398 345

584 502 443 400 343 299 2 567 482 424 376 316 272

490 420 370 334 284 243 3 471 402 353 312 256 219

585 504 449 403 347 306 1 562 485 428 382 319 277

397 343 304 271 228 196 2 382 328 286 254 205 171

301 258 227 199 163 136 3 287 244 212 185 144 115

480 415 370 330 282 248 1 462 403 353 313 260 224

292 252 220 194 157 132 2 279 239 207 180 140 112

208 175 149 128 97 73 3 197 164 138 116 83 57

714 618 546 480 444 427 1 714 604 534 474 406 373

566 487 431 377 344 323 2 564 477 417 371 317 284

471 408 359 312 280 259 3 464 393 341 302 253 226

560 485 433 379 342 329 1 553 474 416 371 312 280

378 328 287 250 219 198 2 371 315 274 243 194 167

284 243 211 180 150 125 3 276 233 199 173 133 105

456 396 355 306 274 261 1 451 388 339 302 248 222

271 233 202 171 142 119 2 266 227 193 167 128 100

190 158 132 108 77 46 3 182 151 124 102 69 38

18

6

12

18

Additional number of colposcopy referrals per additional cancer prevented (compared to current guidelines) Screening frequency (years) Number

18

6

12

18

6 6

12 12

(16)

16 Supplementary Figure 14. The reduction in cervical cancer incidence (compared to no screening) when assuming HPV test

sensitivity of 90%: The average value across the 50 parameter sets for the sensitivity analysis.

3 4 5 6 8 10 3 4 5 6 8 10

94.6 % 93.7 % 92.9 % 91.7 % 89.4 % 87.4 % 1 93.3 % 92.6 % 91.7 % 90.9 % 89.1 % 87.3 % 94.3 % 93.3 % 92.5 % 91.2 % 88.6 % 86.5 % 2 93.1 % 92.2 % 91.3 % 90.4 % 88.3 % 86.4 % 94.1 % 93.1 % 92.1 % 90.7 % 88.1 % 85.9 % 3 92.9 % 92.0 % 91.1 % 90.0 % 87.8 % 85.8 % 94.2 % 93.4 % 92.5 % 91.5 % 89.1 % 87.2 % 1 93.1 % 92.2 % 91.5 % 90.5 % 88.7 % 87.0 % 93.8 % 92.9 % 91.8 % 90.7 % 88.3 % 86.2 % 2 92.6 % 91.7 % 91.0 % 89.8 % 88.1 % 86.1 % 93.5 % 92.5 % 91.4 % 90.2 % 87.7 % 85.5 % 3 92.4 % 91.4 % 90.6 % 89.5 % 87.5 % 85.7 % 94.1 % 93.2 % 92.2 % 91.2 % 88.9 % 86.9 % 1 92.8 % 91.9 % 91.2 % 90.4 % 88.5 % 86.7 % 93.3 % 92.4 % 91.3 % 90.3 % 87.9 % 85.8 % 2 92.2 % 91.2 % 90.4 % 89.5 % 87.6 % 85.8 % 92.8 % 91.8 % 90.7 % 89.8 % 87.3 % 85.0 % 3 91.8 % 90.8 % 89.9 % 88.9 % 87.1 % 85.3 % 92.1 % 91.4 % 90.6 % 89.9 % 87.7 % 85.6 % 1 91.2 % 90.7 % 90.0 % 89.4 % 87.7 % 86.2 % 91.9 % 91.1 % 90.2 % 89.5 % 87.2 % 85.0 % 2 91.1 % 90.4 % 89.8 % 89.1 % 87.3 % 85.7 % 91.8 % 90.8 % 89.9 % 89.2 % 86.8 % 84.6 % 3 90.9 % 90.3 % 89.6 % 88.8 % 87.0 % 85.3 % 92.0 % 91.3 % 90.4 % 89.8 % 87.7 % 85.6 % 1 91.1 % 90.6 % 90.0 % 89.2 % 87.7 % 86.2 % 91.6 % 90.8 % 90.0 % 89.2 % 87.1 % 84.9 % 2 90.8 % 90.2 % 89.5 % 88.7 % 87.2 % 85.7 % 91.4 % 90.6 % 89.6 % 88.9 % 86.7 % 84.5 % 3 90.6 % 90.0 % 89.3 % 88.5 % 86.8 % 85.3 % 91.8 % 91.1 % 90.1 % 89.6 % 87.5 % 85.5 % 1 91.0 % 90.3 % 89.8 % 89.1 % 87.6 % 86.1 % 91.3 % 90.4 % 89.5 % 88.8 % 86.8 % 84.8 % 2 90.6 % 89.8 % 89.2 % 88.5 % 87.0 % 85.5 % 90.9 % 90.0 % 89.1 % 88.4 % 86.3 % 84.2 % 3 90.3 % 89.5 % 88.9 % 88.1 % 86.6 % 85.0 %

12 12

18 18

6 6

12 12

18 18

6 6

(17)

17 Supplementary Figure 15. The reduction in cervical cancer incidence (compared to no screening) when assuming perfect

colposcopy characteristics: The average value across the 50 parameter sets for the sensitivity analysis.

3 4 5 6 8 10 3 4 5 6 8 10

96.6 % 96.4 % 96.4 % 96.2 % 95.7 % 95.4 % 1 95.5 % 95.4 % 95.2 % 95.2 % 94.9 % 94.7 % 96.6 % 96.5 % 96.4 % 96.2 % 95.7 % 95.5 % 2 95.4 % 95.2 % 95.1 % 95.1 % 94.8 % 94.5 % 96.6 % 96.5 % 96.4 % 96.1 % 95.7 % 95.5 % 3 95.4 % 95.3 % 95.1 % 95.1 % 94.8 % 94.5 % 96.4 % 96.3 % 96.2 % 96.0 % 95.6 % 95.3 % 1 95.3 % 95.1 % 95.0 % 94.9 % 94.6 % 94.3 % 96.3 % 96.2 % 96.0 % 95.8 % 95.4 % 95.1 % 2 95.2 % 95.0 % 94.9 % 94.8 % 94.6 % 94.2 % 96.3 % 96.1 % 95.9 % 95.8 % 95.4 % 95.0 % 3 95.1 % 95.0 % 94.8 % 94.7 % 94.5 % 94.1 % 96.3 % 96.2 % 96.1 % 95.9 % 95.5 % 95.1 % 1 95.1 % 94.9 % 94.8 % 94.7 % 94.4 % 94.0 % 96.0 % 95.9 % 95.7 % 95.6 % 95.1 % 94.6 % 2 94.9 % 94.7 % 94.6 % 94.5 % 94.1 % 93.7 % 95.8 % 95.7 % 95.5 % 95.4 % 94.9 % 94.3 % 3 94.8 % 94.6 % 94.4 % 94.4 % 93.9 % 93.5 % 94.4 % 94.1 % 93.9 % 94.0 % 93.1 % 92.4 % 1 93.5 % 93.5 % 93.3 % 93.3 % 92.8 % 92.4 % 94.3 % 94.1 % 93.9 % 93.9 % 93.0 % 92.4 % 2 93.5 % 93.4 % 93.3 % 93.2 % 92.8 % 92.3 % 94.3 % 94.1 % 93.9 % 93.9 % 93.0 % 92.3 % 3 93.5 % 93.4 % 93.3 % 93.2 % 92.8 % 92.3 % 94.3 % 94.0 % 93.8 % 93.9 % 93.0 % 92.2 % 1 93.5 % 93.3 % 93.2 % 93.1 % 92.7 % 92.2 % 94.2 % 93.9 % 93.8 % 93.7 % 92.9 % 92.1 % 2 93.4 % 93.2 % 93.2 % 93.0 % 92.7 % 92.2 % 94.1 % 93.9 % 93.7 % 93.7 % 92.8 % 92.0 % 3 93.3 % 93.2 % 93.1 % 93.0 % 92.6 % 92.1 % 94.2 % 93.9 % 93.7 % 93.7 % 92.9 % 92.1 % 1 93.4 % 93.2 % 93.1 % 93.0 % 92.7 % 92.1 % 94.0 % 93.8 % 93.5 % 93.6 % 92.7 % 91.8 % 2 93.2 % 93.1 % 93.0 % 92.9 % 92.5 % 91.9 % 93.9 % 93.6 % 93.4 % 93.4 % 92.5 % 91.6 % 3 93.2 % 93.0 % 92.9 % 92.8 % 92.4 % 91.8 %

12 12

18 18

6 6

12 12

18 18

6 6

(18)

18 Supplementary Figure 16. Relative colposcopy referral rates (compared to current Norwegian guidelines) when assuming HPV test sensitivity of 90%: The average value across the 50 parameter sets for the sensitivity analysis.

3 4 5 6 8 10 3 4 5 6 8 10

4.17 3.62 3.24 2.93 2.50 2.23 1 3.64 3.16 2.82 2.58 2.21 1.97

3.33 2.91 2.61 2.37 2.04 1.82 2 2.93 2.55 2.30 2.11 1.82 1.63

2.84 2.49 2.24 2.04 1.76 1.58 3 2.51 2.21 1.99 1.83 1.59 1.43

3.45 3.03 2.72 2.49 2.14 1.91 1 3.02 2.65 2.39 2.19 1.90 1.70

2.53 2.25 2.04 1.87 1.63 1.46 2 2.25 2.01 1.83 1.69 1.48 1.34

2.08 1.86 1.70 1.57 1.37 1.24 3 1.88 1.69 1.55 1.44 1.27 1.16

2.98 2.64 2.38 2.19 1.90 1.70 1 2.62 2.32 2.11 1.94 1.70 1.53

2.08 1.87 1.70 1.58 1.38 1.25 2 1.87 1.69 1.55 1.44 1.28 1.17

1.70 1.54 1.41 1.31 1.16 1.05 3 1.57 1.42 1.31 1.23 1.10 1.01

3.25 2.82 2.51 2.31 1.95 1.73 1 2.94 2.58 2.32 2.13 1.84 1.64

2.64 2.30 2.07 1.92 1.64 1.46 2 2.41 2.13 1.93 1.78 1.56 1.40

2.28 2.00 1.81 1.68 1.45 1.29 3 2.09 1.87 1.70 1.58 1.39 1.26

2.72 2.39 2.15 1.99 1.70 1.52 1 2.47 2.20 2.00 1.84 1.62 1.46

2.05 1.83 1.67 1.56 1.36 1.22 2 1.90 1.71 1.58 1.47 1.31 1.20

1.74 1.56 1.44 1.35 1.19 1.08 3 1.62 1.48 1.37 1.29 1.16 1.07

2.37 2.11 1.91 1.78 1.54 1.38 1 2.17 1.95 1.79 1.66 1.47 1.33

1.73 1.56 1.44 1.35 1.19 1.08 2 1.62 1.48 1.38 1.29 1.17 1.07

1.47 1.34 1.24 1.17 1.05 0.96 3 1.39 1.28 1.20 1.14 1.04 0.96

Relative colposcopy referral rates (compared to current guidelines)

Screening frequency (years) Screening frequency (years)

12

18 6 6

12

18

6

12

18 6

12

18 Number

(19)

19 Supplementary Figure 17. Relative colposcopy referral rates (compared to current Norwegian guidelines) when assuming perfect colposcopy characteristics: The average value across the 50 parameter sets for the sensitivity analysis.

3 4 5 6 8 10 3 4 5 6 8 10

4.65 4.11 3.73 3.41 2.96 2.66 1 4.05 3.58 3.24 2.98 2.60 2.33

3.91 3.49 3.18 2.92 2.55 2.30 2 3.42 3.05 2.78 2.57 2.25 2.03

3.44 3.08 2.82 2.60 2.28 2.06 3 3.02 2.71 2.48 2.30 2.03 1.84

3.87 3.46 3.15 2.90 2.54 2.29 1 3.39 3.02 2.75 2.54 2.23 2.02

2.96 2.67 2.45 2.27 2.01 1.82 2 2.62 2.37 2.18 2.02 1.80 1.64

2.47 2.24 2.07 1.93 1.71 1.56 3 2.21 2.01 1.86 1.74 1.56 1.43

3.35 3.02 2.76 2.56 2.24 2.03 1 2.94 2.65 2.42 2.25 1.99 1.80

2.40 2.19 2.02 1.89 1.68 1.53 2 2.15 1.96 1.82 1.70 1.53 1.40

1.96 1.80 1.67 1.57 1.40 1.28 3 1.79 1.64 1.53 1.44 1.30 1.20

3.61 3.18 2.87 2.66 2.28 2.03 1 3.25 2.90 2.63 2.44 2.12 1.90

3.07 2.73 2.48 2.31 1.99 1.78 2 2.78 2.50 2.29 2.13 1.87 1.69

2.72 2.44 2.23 2.08 1.81 1.63 3 2.48 2.25 2.07 1.93 1.71 1.55

3.03 2.70 2.46 2.29 1.98 1.78 1 2.75 2.47 2.27 2.10 1.86 1.68

2.37 2.14 1.97 1.85 1.62 1.47 2 2.17 1.98 1.84 1.72 1.54 1.41

2.02 1.84 1.70 1.61 1.42 1.30 3 1.87 1.72 1.60 1.51 1.37 1.26

2.65 2.38 2.18 2.04 1.78 1.60 1 2.41 2.19 2.02 1.88 1.68 1.52

1.97 1.80 1.66 1.57 1.40 1.28 2 1.82 1.68 1.57 1.48 1.34 1.24

1.66 1.52 1.42 1.35 1.21 1.12 3 1.55 1.45 1.36 1.29 1.18 1.10

Relative colposcopy referral rates (compared to current guidelines)

Screening frequency (years) Screening frequency (years)

12

18 6 6

12

18

6

12

18 6

12

18 Number

(20)

20 Supplementary Figure 18. Relative colposcopy referral rates (compared to current cytology-based guidelines in the United States) under base-case assumptions: The average value across the 50 parameter sets for the sensitivity analysis.

3 4 5 6 8 10 3 4 5 6 8 10

2.70 2.39 2.17 1.98 1.72 1.55 1 2.36 2.08 1.89 1.74 1.51 1.36

2.27 2.02 1.84 1.69 1.48 1.33 2 1.99 1.77 1.61 1.49 1.31 1.18

1.99 1.79 1.63 1.51 1.33 1.20 3 1.76 1.58 1.44 1.34 1.18 1.08

2.24 2.00 1.82 1.68 1.47 1.33 1 1.96 1.75 1.60 1.48 1.30 1.17

1.71 1.55 1.42 1.32 1.17 1.06 2 1.52 1.38 1.27 1.18 1.05 0.96

1.44 1.31 1.21 1.13 1.01 0.92 3 1.29 1.18 1.10 1.03 0.92 0.85

1.94 1.75 1.60 1.48 1.30 1.18 1 1.71 1.54 1.41 1.31 1.16 1.05

1.40 1.28 1.18 1.10 0.98 0.90 2 1.26 1.15 1.07 1.00 0.90 0.83

1.16 1.06 0.99 0.93 0.84 0.77 3 1.06 0.97 0.91 0.86 0.78 0.72

2.11 1.86 1.67 1.55 1.33 1.18 1 1.91 1.70 1.54 1.43 1.25 1.12

1.79 1.59 1.45 1.35 1.17 1.05 2 1.63 1.46 1.34 1.25 1.10 1.00

1.59 1.42 1.30 1.22 1.06 0.96 3 1.45 1.32 1.21 1.13 1.01 0.92

1.76 1.57 1.43 1.34 1.16 1.04 1 1.61 1.45 1.33 1.23 1.09 0.99

1.38 1.25 1.15 1.08 0.96 0.87 2 1.27 1.17 1.08 1.02 0.91 0.84

1.19 1.08 1.01 0.95 0.85 0.77 3 1.10 1.02 0.95 0.90 0.82 0.76

1.54 1.39 1.27 1.19 1.04 0.94 1 1.41 1.28 1.19 1.11 0.99 0.90

1.16 1.06 0.98 0.93 0.83 0.76 2 1.08 1.00 0.94 0.88 0.80 0.74

0.99 0.91 0.85 0.81 0.73 0.68 3 0.93 0.87 0.82 0.78 0.72 0.67

Relative colposcopy referral rates (compared to US guidelines) Screening frequency (years) Number

6 6

12 12

18 18

6 6

12 12

18 18

(21)

21 Supplementary Figure 19. The number of colposcopy referrals per cancer prevented (compared to no screening) when assuming HPV test sensitivity of 90%: The average value across the 50 parameter sets for the sensitivity analysis.

3 4 5 6 8 10 3 4 5 6 8 10

68.5 59.9 54.1 49.6 43.5 39.6 1 60.5 52.9 47.8 44.0 38.5 35.0

54.9 48.4 43.9 40.4 35.6 32.6 2 48.8 43.0 39.0 36.2 31.9 29.3

46.8 41.5 37.8 35.0 31.0 28.5 3 41.9 37.2 33.9 31.5 28.1 25.9

56.8 50.3 45.7 42.2 37.3 34.1 1 50.4 44.6 40.6 37.5 33.2 30.4

41.9 37.6 34.4 32.0 28.6 26.3 2 37.7 33.9 31.2 29.1 26.1 24.1

34.6 31.3 28.8 27.0 24.2 22.4 3 31.6 28.6 26.5 24.9 22.5 20.9

49.1 44.0 40.1 37.2 33.1 30.4 1 43.8 39.2 35.9 33.3 29.7 27.4

34.5 31.3 28.9 27.1 24.3 22.6 2 31.5 28.7 26.6 25.0 22.6 21.1

28.5 26.0 24.1 22.7 20.6 19.2 3 26.5 24.2 22.6 21.4 19.6 18.3

54.7 47.8 42.9 39.8 34.5 31.3 1 49.9 44.1 39.8 36.9 32.5 29.5

44.4 39.2 35.5 33.2 29.1 26.6 2 40.9 36.5 33.3 31.0 27.6 25.4

38.4 34.2 31.2 29.2 25.8 23.7 3 35.6 32.0 29.4 27.5 24.7 22.9

45.8 40.5 36.9 34.3 30.1 27.5 1 42.0 37.6 34.4 32.0 28.6 26.2

34.7 31.3 28.8 27.1 24.2 22.3 2 32.3 29.4 27.3 25.6 23.3 21.6

29.5 26.7 24.8 23.5 21.2 19.7 3 27.7 25.4 23.8 22.5 20.7 19.4

40.0 35.8 32.8 30.7 27.2 25.0 1 36.9 33.4 30.8 28.8 25.9 23.9

29.4 26.8 24.9 23.6 21.3 19.8 2 27.6 25.5 23.9 22.6 20.7 19.4

25.0 23.0 21.5 20.5 18.8 17.6 3 23.8 22.2 20.9 20.0 18.5 17.5

12 12

18 18

6 6

12 12

18 18

6 6

(22)

22 Supplementary Figure 20. The number of colposcopy referrals per cancer prevented (compared to no screening) when assuming perfect colposcopy characteristics: The average value across the 50 parameter sets for the sensitivity analysis.

3 4 5 6 8 10 3 4 5 6 8 10

87.4 77.5 70.4 64.6 56.3 50.8 1 77.0 68.2 61.9 57.0 49.7 44.8

73.6 65.8 60.0 55.3 48.5 43.9 2 65.2 58.1 53.0 49.1 43.1 39.1

64.7 58.2 53.2 49.2 43.4 39.3 3 57.6 51.7 47.4 44.0 38.9 35.4

73.0 65.3 59.6 55.0 48.4 43.8 1 64.5 57.7 52.7 48.7 42.9 38.9

55.9 50.6 46.5 43.2 38.3 35.0 2 49.9 45.3 41.7 38.8 34.7 31.7

46.7 42.5 39.3 36.7 32.7 30.0 3 42.2 38.5 35.7 33.4 30.0 27.6

63.3 57.1 52.2 48.5 42.8 39.0 1 56.2 50.6 46.5 43.2 38.3 34.9

45.5 41.6 38.4 35.9 32.1 29.5 2 41.2 37.6 34.9 32.8 29.5 27.2

37.3 34.2 31.8 29.9 26.9 24.8 3 34.2 31.5 29.4 27.8 25.2 23.4

69.3 61.3 55.5 51.3 44.5 39.9 1 63.0 56.3 51.0 47.4 41.5 37.4

59.0 52.6 47.9 44.6 39.0 35.2 2 53.9 48.6 44.5 41.4 36.6 33.3

52.3 47.0 43.1 40.2 35.4 32.1 3 48.1 43.6 40.2 37.5 33.4 30.5

58.3 52.2 47.6 44.3 38.8 35.0 1 53.3 48.0 44.1 41.0 36.4 33.1

45.6 41.4 38.1 35.8 31.8 29.0 2 42.1 38.5 35.8 33.5 30.2 27.8

38.9 35.5 33.0 31.2 27.9 25.7 3 36.3 33.4 31.2 29.5 26.8 24.9

51.0 46.0 42.2 39.5 34.8 31.7 1 46.8 42.6 39.4 36.7 32.8 30.1

38.0 34.8 32.3 30.6 27.5 25.3 2 35.4 32.7 30.7 29.0 26.4 24.5

32.0 29.6 27.7 26.3 23.9 22.2 3 30.3 28.2 26.6 25.3 23.3 21.8

12 12

18 18

6 6

12 12

18 18

6 6

(23)

23 References

Cancer Registry of Norway. Annual Report of the Norwegian Cervical Cancer Screening Program, 2009-11. Accessed at https://www.kreftregisteret.no/globalassets/publikasjoner-og- rapporter/livmorhalskreft/arsrapport/aarsrapport_2009-2011_livmorhalskreft.pdf on February 12, 2013. Oslo: Cancer Registry of Norway, 2012.

Cancer Registry of Norway. Annual Report of the Norwegian Cervical Cancer Screening Program, 2012. Accessed at https://www.kreftregisteret.no/globalassets/publikasjoner-og- rapporter/livmorhalskreft/arsrapport/aarsrapport_livmorhals_2012.pdf on June 8, 2015. Oslo:

Cancer Registry of Norway, 2013.

Cancer Registry of Norway. Annual Report of the Norwegian Cervical Cancer Screening Program, 2013-14. Accessed at https://www.kreftregisteret.no/globalassets/publikasjoner-og- rapporter/livmorhalskreft/arsrapport/livmorhals_2015.pdf on October 16, 2015. Oslo: Cancer Registry of Norway, 2015.

Norwegian Technical Appendix. Harvard Cervical Cancer Natural History Model Calibration and Costing Approach for Norway. Accessed at

http://www.med.uio.no/helsam/english/research/projects/preventive-strategies-hpv/17- harvardmodel-norway-technicalappendix.pdf on May 10, 2017. 2017.