Cost effectiveness of prophylactic HPV 16/18 vaccination in Finland: results from a modelling exercise

Figures & data

Figure 1. Schematic structure of the model. CIN, cervical intraepithelial neoplasia; det, detected; HPV, human papillomavirus.

Table 1.  Transition probabilities.

Item	Base-case value	References
Normal to HPV	0–0.12	[9–13]
HPV to CIN 1	0.049	[14]
CIN 1 to CIN 2–3	0.091	[15–17]
CIN 2–3 to persistent CIN 2–3	0.114	[15],[16]
HPV clearance to normal	0.449	[18–22]
CIN 1 clearance	0.236	[15–17]
CIN 2–3 clearance	0.227	[15–17]
Persistent CIN 2–3 to cancer	0–0.10	Assumption

CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus.

Table 2.  Organised cervical cancer mass screening programme in Finland 2005^[24].

Targeted population	Target population 31.12.2004	Number invited	Invited (% of population)	Number screened	Screened (% of invited)
5-yearly screening*
25	29,567	10,305	34.9	5864	56.9
30^†	30,368	28,098	92.5	16,652	59.3
35^†	30,191	29,300	97.0	18,806	64.2
40^†	34,980	34,257	98.2	23,877	69.5
45^†	35,923	35,275	98.2	25,591	72.5
50^†	37,500	36,976	98.6	27,976	75.7
55^†	39,039	37,892	97.1	29,046	76.7
60^†	35,657	33,675	94.4	26,283	78.0
65	23,293	3515	15.1	2727	77.6
30–60^†	243,658	236,690	97.1	168,892	71.4

*Age groups are defined on the basis of the invitation year and the birth year.

^†Age groups targeted in the Decree on Public Health (1992).

Table 3.  Model input data.

Item	Base-case value	References
Screening
Start and stop age (years)
Organised mass screening (5-year interval)	30–60	[24],[25]
Paps outside organised mass screening	17–85	[24],[25]
Modelled screening coverage* (combined mass screening + Pap smears outside mass screening)		Extrapolated^[24],^[25]
% screened every 2 years (25–70)	70
% screened every 2–4 years (17–75)	24
% never screened in lifetime	6
Test characteristics		[29–31]
Sensitivity (CIN 1)	0.65
Sensitivity (CIN 2–3)	0.81
Vaccination
Efficacy
Against Cervical cancer	0.77	=0.74*0.95 + 0.26*0.27 = 0.77[7],[27],[32–34]
Against CIN 1	0.52	=0.37*0.95 + 0.63*0.27 = 0.52[7],[27],[32–34]
Against CIN 2/3	0.65	=0.52*0.95 + 0.48*0.27 = 0.65[7],[27],[32–34]
Duration of efficacy	Lifelong	Assumed
Age	11	Assumed
Vaccination coverage	90%	Assumed
Cancer stage distribution
Stage I	52%	Oulu and Turku University hospitals (FIGO)[35] and Helsinki University hospital (unpublished information)
Stage II	32%
Stage III	9%
Stage IV	7%

*Current mass screening is every 5 years from 30 to 60 years; this does not match with observed annual Pap smears taken each year[25], therefore screening frequency has been increased to match the observed number of Pap smears taken.

CIN, cervical intraepithelial neoplasia.

Table 4.  Cost and utility data.

Item	Base-case value	Reference
Vaccine cost per dose	€77.24	[40]
Cancer treatment	€10,017	[37–39]
Screening & CIN treatment newly detected (year 1)		[23]
Regular screening negative Pap	€41.50	[37–39]
Regular screening + positive Pap	€66.71	[37–39]
CIN 1 detected	€783.59	[23],[37]
Pap test	€41.50	[37–39]
Colposcopy	€420	[37–39]
Treatment (for 70% of the patients)	€460	[37–39]
CIN 2/3 detected	€921.59	[23]
Pap test	€41.50	[37–39]
Colposcopy/biopsy	€420	[37–39]
Treatment	€460	[37–39]
CIN treatment year following detection (year 2)		[23]
CIN 1, year 2	€438.51	[23]
Pap test (95% of patients)	€41.50	[37–39]
Colposcopy (95% of patients)	€420	[37–39]
CIN 2/3, year 2	€536.80	[23]
Pap test (×2 for 90% of patients)	€41.50	[37–39]
Colposcopy (×2 for 55% of patients)	€420	[37–39]
Utilities
Stages
No HPV, HPV infection, CIN1/2/3	1
CIN1 detected	0.987	[41–43]
CIN2/3 detected	0.991	[41–43]
Cancer treated	0.727	[41–43]
Cancer cured	0.938	[41–43]
Death	0

*Different for each stage I–IV.

^†Same for Pap smear + different for confirmatory test/follow-up.

Ranges (±25%) for the parameters not known were used in the probabilistic analysis.

CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus.

Figure 2. (a) Comparison between model-predicted and observed data for age-specific cervical cancer incidence and (b) cervical cancer mortality.

Figure 3. Results of probabilistic sensitivity analysis expressed as cost-acceptability curves, for screening plus vaccination and screening alone.

Table 5.  Effect of vaccination on clinical endpoints.

	Current situation (average last 15 years)	Modelled current situation	Base-case, vaccination coverage 90%	Base-case vs. modelled current situation
Treated CIN 2/3 cases	2000–2500	2088	873	–58%
Cervical cancer cases	155	178	52	–71%
Cervical cancer deaths	66	74	20	–73%
Cervical cancer deaths <60 years	17	18	6	–67%

CIN, cervical intraepithelial neoplasia.

Table 6.  Cost-effectiveness results (cohort of 30,000 girls; lifetime horizon).

	Total costs	QALY	Life-years	Cost per QALY	Cost per life-year
Discounted at 3%, vaccine coverage 90%
Current screening + vaccination	€21,339,261	896,518	926,629	—	—
Current screening	€16,584,277	896,243	926,496	—	—
Incremental	€4,754,984	275	133	€17,294	€35,806
Discounted at 0%, vaccine coverage 90%
Current screening + vaccination	€46,206,881	2,191,143	2,191,494	—	—
Current screening	€43,065,736	2,189,931	2,190,700	—	—
Incremental	€3,141,145	1212	794	€2592	€3956

QALY, quality-adjusted life-year.

Moscicki AB, Hills N, Shiboski S, et al. Risks for incident human papillomavirus infection and low-grade squamous intraepithelial lesion development in young females. JAMA 2001; 285: 2995–3002

 PubMed Web of Science ®Google Scholar

Holowaty P, Miller AB, Rohan T, et al. Natural history of dysplasia of the uterine cervix. J Natl Cancer Inst 1999; 91: 252–258

 PubMedGoogle Scholar

Melnikow J, Nuovo J, Willan AR, et al. Natural history of cervical squamous intraepithelial lesions: a meta-analysis. Obstet Gynecol 1998; 92: 727–735

 PubMed Web of Science ®Google Scholar

Finnish Cancer Registry. http://www.cancerregistry.fi. 2007

 Google Scholar

Monto K, Nieminen P. Gynekologisten irtosolunäytteiden määrät ja raportointitavat Suomessa. Suom Lääkäril 2005; 18-19/2005: 2093–2097

 Google Scholar

Smith JS, Lindsay L, Hoots B, et al. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int J Cancer 2007; 121: 621–632

 PubMed Web of Science ®Google Scholar

Paavonen J, Jenkins D, Bosch F, et al. Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial. Lancet 2007; 369: 2161–2170

 PubMed Web of Science ®Google Scholar

FIGO. (International Federation of Gynecology and Obstetrics) 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet 2006; 95(Suppl 1)S1–257

 Google Scholar

Price SLD, [Finnish Pharmaceutical Data Ltd/Suomen Lääkedata Oy; 2008

 Google Scholar

lääkäriseura Duodecimin ja Suomen kolposkopiayhdistyksen asettama työryhmä. Suomalaisen. Käypä hoito -suositus: Kohdunkaulan, emättimen ja ulkosynnytinten solumuutokset - diagnostiikka, hoito ja seuranta. Duodecim 2006; 122: 1808–1833

 Google Scholar

Hujanen T, Kapiainen S, Tuominen U, et al, Terveydenhuollon yksikkökustannukset Suomessa vuonna 2006 (Healthcare unit costs in Finland 2006). 3/2008, 1–107. 2008. Helsinki, Stakes. Työpapereita

 Google Scholar