1. Cost-effectiveness Analysis for Cervical Cancer Screening Using HPV DNA Tests in Chile Franco Figueira S, BPharm student1; Cachoeira CV, MD, MBA1; Silva M, MD2; Kano BY, BPharm student1; Souza FH, MD, PhD1; Poulios, N, PhD, PhM 3
1Roche Diagnostics LATAM; 2Roche Diagnostics Chile; 3Roche Molecular USA

2. Disclaimer Potential conflict of interest
Market Access and Health Technology Assessment Regional Manager at Roche Diagnostics LATAM
ISPOR Latin America Health Technology Producers (Industry) Committee member
2.3 billion women over the age of 15 are at risk of contracting cervical cancer worldwide.1
There are nearly 530,000 new cases of cervical cancer each year.2
Global crude incidence of cervical cancer is 15.6 per 100,000 women per year (between 16.3 and 13.0 in developing and developed regions).2
Peak incidence in developed countries is years of age, impacting women in the prime of their lives with significant impact to families, employers and communities.
Death attributed to cervical disease among women is in the top four causes of cancer-related deaths worldwide (Figure 1).3
2 GLOBOCAN (2012) Cervix uteri Estimated incidence and prevalence

3. Background Cervical Cancer Epidemiology
Figure 1. Most incident cancers in women, Chile, 2012¹
Figure 2. Worldwide cervical cancer incidence and mortality by region¹
2.3 billion women over the age of 15 are at risk of contracting cervical cancer worldwide.1
There are nearly 530,000 new cases of cervical cancer each year.2
Global crude incidence of cervical cancer is 15.6 per 100,000 women per year (between 16.3 and 13.0 in developing and developed regions).2
Peak incidence in developed countries is years of age, impacting women in the prime of their lives with significant impact to families, employers and communities.
Death attributed to cervical disease among women is in the top four causes of cancer-related deaths worldwide (Figure 1).3
2 GLOBOCAN (2012) Cervix uteri Estimated incidence and prevalence
Age Standardized Rate (ASR) / 100,000
1 – GLOBOCAN (2012) World Cancer Population fact sheet

4. Background - HPV Role of Human Papillomavirus (HPV) in cervical cancer
As the leading cause of CIN, HPV is also the leading cause of cervical cancer and it`s present in 99.7% of cervical cancer specimens.2
CIN1 carries the lowest risk and will typically be cleared by the immune system
CIN2 is associated with moderate dysplasia and if untreated will often progress to CIN3
CIN3 is associated with severe dysplasia and is a large risk factor for cervical cancer. Also, CIN3 is, sometimes, referred to carcinoma in situ
Figure 4. Natural progression of HPV infection¹
Figure 3. Risk of developing ≥CIN3 in 3yrs 3
HPV infection is the leading cause of cervical cancer
HPV infection is the leading cause of cervical intraepithelial neoplasia (CIN) which is the potentially premalignant, abnormal growth (dysplasia) of squamous cells on the surface of the cervix.
CIN is classified into 3 stages of progressive severity and risk (Figure 2).
CIN: Cervical Intraepithelial Neoplasia
1- Lipsy RJ. et Am J Manag al. (2008) Care; 14: S177-S184 ; 2- Wright TC Jr et al. (2010) Gynecol Oncol. 136 (2015) ; 3- Adapted from Ciaran B. J. Woodman et al Nature Reviews Cancer 7, 11-22

5. Cost-effectiveness analysis for Cervical Cancer screening using HPV DNA tests in Chile

6. Objectives and Methods
Estimate the cost-effectiveness of cervical cancer primary
screening with HPV DNA Genotyping tests in Chile
Design
Markov Model
Population
1,000 non-hysterectomized women ages ≥30 and ≤64 years
Perspective
Public Payer
Comparators
1) Cytology alone; 2) Pooled HPV DNA test; 3) HPV DNA with
16/18 genotyping test
Screening interval: 3 years (strategy 1) and 5 years (strategy 2, 3)
Costs
Screening, office visits, pre-malignant lesions and cancer
treatment costs. Source: FONASA (converted to USD, 2014)
Outcomes
Cost per patient, ICUR and ICER
Epidemiological data
ATHENA trial study, WHO database and literature
Miscellaneous
Discounting: 3% annually; Time horizon: 40 years
Sensitivity analysis
Deterministic (One-way sensitivity analysis: +20% & -20%)

7. Data Epidemiology Diagnostic Screening Performance
Sensitivity (CIN 2,3)
Specificity
(CIN 2,3)
Cytology³
36,3%
98,7%
HPV DNA 16/18 genotyping
w/ reflex cytology4
72%
85,2%
HPV-16/18 , % (all ages)1
3,1%
HPV-16/18, % of hrHPV(+)¹
15,0%
hrHPV non-16/18,
% of hrHPV(+)¹
85,0%
HPV-16/18, % per cytology
Normal¹
2,5%
ASC-US¹
44,7%
LSIL/HSIL¹
71,0%
Cervical cancer¹
85,8%
CIN 2,3 in hrHPV (+),
% (ages ≥21 ys)
All¹
4,9%
ASC-US²
16,3%
LSIL/HSIL²
37,5%
hrHPV (+) in CIN 2,3, %²
92,6%
HPV 16/18 in CIN 2,3,
% of hrHPV CIN 2,3²
54,6%
Non-16/18 hrHPV in
cervical cancer,%²
25,0%
1- ICO (Institut Català dOncologia) – HPV and Related Diseasse Report – Chile; 2- ATHENA (Addressing  THE  Need for  Advanced HPV Diagnostics) trial study; 3- Ferreccio et al. (2013) Int. J. Cancer: 132, 916–923; 4- Cox JT, et al (2012) Am J Obstet Gynecol ;208:1.e1-1.e11.

8. Methods Markov model structure
Figure 5. Markov Model
Health Utilities (all ages)¹,²
hrHPV- (well)
1,00
CIN 1*
0,97
CIN 2,3*
Cervical cancer**
0,71
Death from other cause
Death from Cervical Cancer
hrHPV-
hrHPV+
No CIN
CIN 1
CIN 2
CIN 3
Cervical Cancer
A Markov model captured the outcomes of 1,000 non-hysterectomized women ages 25 years and older who transitioned annually across possible health states and were screened over a 45-year period in Brazil
 U.S. National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program
*Assumption based on health utility 0.97 for HSIL reported by Sanders et al (2003).
**Assumption based on health utilities for cervical cancer in treatment phase (0.79 for Stage I and 0.62 for Stages II-IV), weighted by SEER stage distribution for cervical cancer at diagnosis; value represents weighted mean health utility.
1- Sanders GD et al. Cost-effectiveness of a potential vaccine for human papillomavirus. Emerg Infect Dis 2003;9(1):37-48.
2- Institute of Medicine (U.S.). Committee to Study Priorities for Vaccine Development, Stratton KR, Durch J, Lawrence RS. 2003;9(1):37-48.
CIN: Cervical Intraepithelial Neoplasia, HPV: Human Papillomavirus

9. Methods Cervical cancer screening algorithms
1) Cytology alone
2) Pooled HPV with reflex cytology
3) HPV with 16/18 genotyping test and reflex cytology

10. Results Cost Effectiveness Analysis
QALY: Quality-adjusted life year
comparing the diagnosis options
Cost per patient
USD; including screening, diagnosis and treatment
LYG: Life years gained
comparing the diagnosis options
The primary screening with the strategy (3) HPV with 16/18 genotyping and reflex cytology, results in earlier detection of clinically relevant high-grade CIN (Cervical Intraepithelial Neoplasia) at the initial visit along with efficient use of healthcare resource in Brazil.
In addition, the model suggested an Incremental Cost Utility Ratio (ICUR) and Incremental Cost Effectiveness Ratio (ICER) of 13,266 R$/QALY and 51,389 R$/LYG, respectively, comparing the strategies (3) to (1), whereas, the strategy (2) was dominated by strategy (3).
HPV16/18 genotyping test as primary screening is a cost-effective approach for this Brazilian scenario due to the ICER < 2 Brazilian GDP per capita
Cost per patient = screening + diagnosis + treatment (NIC and Cervical Cancer)
Strategies
∆ Cost (USD)
∆ LYG
∆ QALY
Cytology -
Pooled HPV 76
0,004
0,009
HPV with 16/18 genotyping
- 28 (Dominant)
0,007
(Dominant)
0,022

11. Results Deterministic sensibility analysis (one-way)
Variables
20% decrease
20% increase
Colposcopy + biopsy (cost)
HPV DNA Genotyping - Dominant
Treatment NIC 1, 2,3 (cost)
Cytology (cost)
Cervical Cancer Treatment (cost)
HPV DNA genotyping test (cost)
ICER - USD 85/QALY
(cost-effective)
HPV DNA genotyping test (specificity)
HPV DNA genotyping test (sensitivity)
Cytology (specificity)
Cytology (sensitivity)
Annual Discount (Effects)
Annual Discount (Cost)
The primary screening with the strategy (3) HPV with 16/18 genotyping and reflex cytology, results in earlier detection of clinically relevant high-grade CIN (Cervical Intraepithelial Neoplasia) at the initial visit along with efficient use of healthcare resource in Brazil.
In addition, the model suggested an Incremental Cost Utility Ratio (ICUR) and Incremental Cost Effectiveness Ratio (ICER) of 13,266 R$/QALY and 51,389 R$/LYG, respectively, comparing the strategies (3) to (1), whereas, the strategy (2) was dominated by strategy (3).
HPV16/18 genotyping test as primary screening is a cost-effective approach for this Brazilian scenario due to the ICER < 2 Brazilian GDP per capita
Cost per patient = screening + diagnosis + treatment (NIC and Cervical Cancer)

12. Conclusion
HPV with16/18 genotyping test as primary screening for cervical cancer is a cost-saving (dominant) approach at this Chilean scenario. On top of that, clinically wise it may improve protection against cervical cancer.
These results may be achieved by:
Earlier detection of clinically relevant CIN by HPV testing with 16/18 genotyping and proper management
Risk-stratification, which leads to more efficient use of health care resources

13. Gracias Obrigado Thank you