CERVICAL CANCER SCREENING SCENARIOS for pan-canadian Cervical Screening Initiative

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Oswald Blair
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1 CERVICAL CANCER SCREENING SCENARIOS for pan-canadian Cervical Screening Initiative June

2 Acknowledgements Anthony Miller Cathy Popadiuk Claude Nadeau Keiko Asakawa Marc Brisson Michael Wolfson Saima Memon Steve Gribble William Flanagan Zenia Ferreira 2

3 Objectives Target setting: incidence rate What will the incidence rate be in the future if we continue with the status quo? What would the incidence rate be if we increased screening participation to 80%? Altered our screening programs? Introduced primary HPV DNA testing? If we switch to primary HPV DNA testing: What are the health outcomes? How much will it cost? Is it cost-effective in Canada compared to cytology? 3

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5 Assumptions Screening Inputs Baseline assumptions Recruitment period 2015 onward Recruitment age for PAP screening years old (25, 30-69) Interval years between initial rescreen 3 (5, 10) Screening participation 70% Screening modalities Pap or HPV DNA test Vaccination Inputs Baseline assumptions Age 12 Sex Female Vaccine deployment year 2007 Vaccine type Quadrivalent Vaccination coverage 70% (50%, 90%) Proportion protected 100% Degree of protection 100% 5

6 Incidence per 100, Incidence per 100, STATUS QUO 2 1 Triennial PAP 21-69: 70% ppt: No vacc non-age-standardized 6

7 Incidence per 100, Incidence per 100, STATUS QUO + vaccination 2 Triennial PAP 21-69: 70% ppt: No vacc 1 Triennial PAP 21-69: 70% ppt (70%V) non-age-standardized

8 Incidence (per 100,000) 20 Incidence of cervical cancer in If unspecified, age = and interval = x 3 years No vaccine, no screening Vaccine, no screening non-age-standardized 8

9 Mortality per 100, Mortality per 100, STATUS QUO Triennial PAP 21-69: 70% ppt: No vacc non-age-standardized 9

10 Mortality per 100, Mortality per 100, STATUS QUO + vaccination Triennial PAP 21-69: 70% ppt: No vacc Triennial PAP 21-69: 70% ppt: (70%V) non-age-standardized 10

11 Mortality per 100, Mortality per 100, Triennial PAP 21-69: 70% ppt: No vacc Triennial PAP 21-69: 70% ppt: (70%V) Triennial PAP 21-69: 70% ppt (90% V) Herd immunity non-age-standardized 11

12 Mortality (per 100,000) If unspecified, age = and interval = x 3 years Mortality per 100,000 in 2037 No vaccine, no Pap Vaccine, no Pap Triennial PAP 21-69: 70% ppt (70%V) Triennial PAP 25-69: 70%ppt (70% V) Triennial PAP 30-69: 70% ppt (70% V) Triennial PAP 21-69: 80% ppt: No vacc PAP every 5 yrs: 70% ppt: (70%V) Triennial PAP 21-69: 70% ppt: No vacc PAP every 10 years: 70% ppt (70%V) No screening: 70%V No vaccination or screening 12

13 Costs Incremental Cost-Effectiveness Ratios (ICERs) reject (dominated) consider (more expensive but saves more lives) Lives consider (less expensive but saves fewer lives) accept (dominant) 13

14 Total QALYs Thousands 998, , , ,300 Cost-Effectiveness* Vaccine, screen Vaccine, screen Vaccine, screen x 5 years Vaccine, screen x 3, Vaccine, screen x 10 No vaccine, screen x 3, ,200 Vaccine, no screening 998,100 No vaccine, no screening 998,000 $0 $5 $10 $15 $20 $25 $30 $35 $40 Billions Total Costs *3% discount rate 14

15 Cost-effectiveness ratios* Total Cost Total QALYs ICER (in '000,000's) (in '000's) No vaccine, no screening $12, ,016 - Vaccine, no screening $11, ,253 DOMINANT Vaccine, cytology x 10 years $19, ,390 $ 21,000 Vaccine, cytology x 5 years $25, ,448 $ 31,000 Vaccine, cytology x 3 years $29, ,482 $ 38,000 Vaccine, cytology x 3 years $31, ,488 $ 41,000 Vaccine, cytology x 3 years $33, ,491 $ 44,000 No vaccine, cytology x 3 years $35, ,383 $ 64,000 *3% discount rate applied 15

16 Average annual cost ( ) Billions $0.0 $0.5 $1.0 No vaccination or screening No screening: 70%V PAP every 10 years: 70% ppt (70%V) PAP every 5 yrs: 70% ppt: (70%V) Triennial PAP 30-69: 70% ppt (70% V) Triennial PAP 25-69: 70%ppt (70% V) Triennial PAP 21-69: 70% ppt (70%V) Triennial PAP 21-69: 70% ppt (50%V) Triennial PAP 21-69: 70% ppt (90% V) Triennial PAP 21-69: 70% ppt: No vacc Cost of HPV vaccination Screening cost Cost non-cancer treatment (excluding warts) Cost of treating warts Cost of cancer treatment 16

17 Average annual screening cytology count ( ) 3,500,000 3,000,000 2,500,000 2,000,000 1,500,000 1,000, ,000 0 Screening cytology count PAP every 10 years: 70% ppt (70%V) PAP every 5 yrs: 70% ppt: (70%V) Triennial PAP 30-69: 70% ppt (70% V) Triennial PAP 25-69: 70%ppt (70% V) Triennial PAP 21-69: 70% ppt: No vacc Triennial PAP 21-69: 70% ppt (50%V) Triennial PAP 21-69: 70% ppt (70%V) Triennial PAP 21-69: 70% ppt (90% V) 17

18 300,000 Average annual colopscopy count ( ) No vaccination or screening 250, , , ,000 50,000 0 Colopscopy count No screening: 70%V PAP every 10 years: 70% ppt (70%V) PAP every 5 yrs: 70% ppt: (70%V) Triennial PAP 30-69: 70% ppt (70% V) Triennial PAP 25-69: 70%ppt (70% V) Triennial PAP 21-69: 70% ppt (90% V) Triennial PAP 21-69: 70% ppt (70%V) Triennial PAP 21-69: 70% ppt (50%V) Triennial PAP 21-69: 70% ppt: No vacc 18

19 Mortality per 100, Mortality per 100, non-age-standardized *Not comparable to cytology results, but comparable to each other HPV DNA every 5 years (70%V) HPV DNA every 5 years (70%V) No difference in mortality 19

20 Considerations Due to little empirical data on sexual behaviour, long-term data on vaccine efficacy, and existing questions around the development and progression of lesions and HPV-related cancers, higher degree of parameter uncertainty Uncertainty around future performance of cytology due to reduced prevalence Due to very low prevalence of cervical cancer, estimates are subject to higher degree of Monte Carlo uncertainty 20

21 Conclusions By 2037, an incidence of 6 per 100,000 is projected, assuming that screening programs remains unchanged (70% cytology x 3 years in 21-69). Increasing the start age of screening to 25 or 30 has little impact on cervical cancer incidence or mortality and generates cost-savings. Increasing the screening interval to every 5 or 10 years is more cost-effective, however is associated with increased mortality. 21

22 Next Steps Primary HPV DNA testing :cytology, HPV 21-34: cytology, HPV HPV only with cytology triage Different screening strategies in vaccinated vs unvaccinated cohorts Vaccinating boys Oropharyngeal, vulvar, vaginal and anal cancers Vaccine effectiveness or longevity 22

23 Natalie Fitzgerald, Program Manager, Economics, Cancer Risk Management Platform

24 Appendix 24

25 Number of infected females Prevalence of HPV 16/18 1,200,000 1,000, ,000 No vaccination 70% vaccinated 600, , ,000 0 POP (lifetime) 25

26 Number of infected females Prevalence of HPV 16/18 1,200,000 1,000, , ,000 No vaccination 50% vaccinated 70% vaccinated 90% vaccinated 400, ,000 0 POP (lifetime) 26

27 Incidence (per 100,000) Incidence of cervical cancer in 2037 with varying vaccination rates

28 Mortality (per 100,000) PAP Mortality Rate Triennial PAP 21-69: 70% ppt (90% V) Triennial PAP 21-69: 70% ppt (70%V) Triennial PAP 25-69: 70%ppt (70% V) Triennial PAP 21-69: 70% ppt (50%V) Triennial PAP 30-69: 70% ppt (70% V) Triennial PAP 21-69: 80% ppt: No vacc PAP every 5 yrs: 70% ppt: (70%V) Triennial PAP 21-69: 70% ppt: No vacc non-age-standardized 28

29 Mortality (per 100,000) 5.0 Mortality per 100,000 in non-age-standardized 29

30 Billions Millions $40 $35 $30 $25 $20 $15 $10 $5 $0 Lifetime cost Lifetime cost and QALY * 3% discount 30

31 Murphy et al., Cervical screening: a guideline for clinical practice in Ontario. J Obstet Gynaecol Can, 2012 May; 34(5):

32 Cost of screening test Cytology HPV DNA test Family physician visit $67.82 $67.82 Tray fee $10.99 $10.99 Lab cost - tech $3.12 $3.12 Lab cost - pathologist $93.24 $93.24 Test n/a $85.67 Total $ $

33 Parameter: Cervical cancer screening and pre-cancer treatment costs Types of test and treatment in HPV cervical cancer screening Base case scenario (default) Cytolog y (PAP) screen Cytolog y (PAP) reassess ment Initial colposc opy (withou t biopsy) Reassess ment colposc opy within 6 months (withou t biopsy) Reassess ment colposc opy not within 6 months (withou t biopsy) Biopsy HPV test when recent (<=6 months ) liquid sample already exists HPV test when recent (<=6 months ) liquid sample does not exist Observ ation (do nothing ) Cold knife Leep Cryo Laser Hystere ctomy Warts remova l

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35 Parameter: Sensitivity and specificity of cytology Cytology type - Conventional cytology Scenario - Base case scenario (default) Cytology result Progression status All cells normal Atypical squamous cells of Atypical squamous undetermined cells, maybe high significance (ASC-US) grade lesion (ASC-H) Low grade squamous intraepithelial lesion (CIN1) High grade squamous intraepithelial lesion (CIN2 or CIN3) Atypical glandular cells (AGC) Adenocarcinoma in situ (AIS) Has cervical cancer No infection and no lesion Infected but no lesion Warts CIN CIN CIN Adenocarcinoma in situ (AIS) Cervical cancer

36 Parameter: Sensitivity and specificity of colposcopy Scenario - Base case scenario (default) Colposcopy results Progression status CIN2 or CIN3: lesion satisfactory and visible CIN2 or CIN3: lesion not satisfactory AIS Cervical Cancer Less than LSIL LSIL No infection and no lesion Infected but no lesion Warts CIN CIN CIN Adenocarcinoma in situ (AIS) Cervical cancer

37 Parameter: Sensitivity and specificity of HPV DNA test Scenario - Base case scenario (default) Progression status HPV_INFECTION No infection and no lesion Infected but no lesion Warts CIN1 CIN2 CIN3 Adenocarc inoma in situ (AIS) Cervical cancer Not infected with HPV Infected with HPV

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