Economic consequences of the implementation of primary DNA-HPV genotype testing in Bulgaria

Figures & data

Table 1. Screening algorithm for HPV adapted from Wentzensen et al. [15].

Primary HPV screening
30% of tested women		70 % of tested women
Colposcopy applied in 70% of type 16/18 HPV	Cytology applied in 30% of which: Colposcopy—50% positive Routine screening (annually)—50% negative	Routine screening 5 years in HPV negative

Table 2. Cost data for the pharmacoeconomic methods.

HC resource	NHIF cost (euro)	Source
HPV genotype test	39.78	National Health Insurance Fund (National Framework Agreement 2020–2022) [20].
Dual-stain cytology triage of high-risk genotypes for immediate risk stratification p16-Ki67 (CINTec)	76.70	Roche Data
PAP cytology test	18.10	National Health Insurance Fund (National Framework Agreement 2020–2022) [20]
Colposcopy	20.45	National Health Insurance Fund (National Framework Agreement 2020–2022) [20]
Primary physician visit (general practitioner + gynecologist)	20.20	National Health Insurance Fund (National Framework Agreement 2020–2022) [20]
Primary physician visit (gynecologist)	5.62	National Health Insurance Fund (National Framework Agreement 2020–2022) [20]

Table 3. Distribution of patients and results per approach.

Input data	Value
	HPV testing scenario	Current PAP testing scenario	References
Number of tested women 30–54 (avg per year)	213,715	213,715	National Statistical Institute [23]
HPV tested positive	62,191	36,481	Kovachev et al. [19]; Doorbar et al. [28]
HPV 16/18 positive	43,534	24,771	Kovachev et al. [18]
mortality cervical cancer/year	331	503	Arbin et al. [29]
Saved lives due to reduced mortality	172		–
age of diagnosis/avg	39	39	Liu et al. [30]
age mortality/avg	66	59	National Health Insurance Fund [20]; Arbin et al. [29]
Life year lost (LYL)/woman	8.53	15.53	–
Total LYL	2823	7812	-
Life years gained	4989		-

Table 4. Cost of the testing approaches (euro).

	2023	2024	2025	2026	2027	2028	AVG/year
Total cost of HPV testing	12,979,080	13,509,273	13,562,360	13,594,145	13,606,084	13,599,558
Total cost of colposcopy	1,438,985	1,433,013	1,399,965	1,368,793	1,339,448	1,311,880
Total cost of dual-stain triage testing p16/Ki67 (CINTec triage testing)	1,493,756	1,487,557	1,431,263	1,377,076	1,324,916	1,274,710
Productivity loss		29,163,741	28,177,527	27,224,664	26,304,023	25,414,515
Total direct medical cost	15,911,821	16,429,843	16,393,587	16,340,013	16,270,448	16,186,148	16,324,008
Total direct + indirect costs		45,593,584	44,571,115	43,564,678	42,574,472	41,600,664	43,580,902
Benefits
Total LYG due to early diagnosis and reduced mortality (euro)	51,529,984	51,529,984	51,529,984	51,529,984	51,529,984	51,529,984	51,529,984
Current PAP testing
Costs
	2023	2024	2025	2026	2027	2028	AVG/year
PAP testing	8,287,580	8,253,185	7,940,860	7,640,220	7,350,833	7,072,281
Cost of colposcopy	879,656	561,966	540,699	520,229	500,524	481,557
Productivity loss		80,693,725	77,964,951	75,328,455	72,781,116	70,319,919
Total direct costs (euro)	9,167,236	8,815,151	8,481,559	8,160,449	7,851,357	7,553,838	8,172,471
Total direct + indirect costs		89,508,875	86,446,510	83,488,904	80,632,473	77,873,757	83,590,104

Table 5. Cost-effectiveness analysis of HPV genotype test approach.

LYG
Only direct costs
Alternatives	Cost (euro)	LYG	ΔC (euro)	ΔLYG	ICER
PAP testing	8,172,470.69
HPV testing	16,324,007.98		8,151,537.29	4,988.38	1634
Direct + indirect costs
Alternatives	Cost	LYG	ΔC	ΔLYG	ICER
PAP testing	83,590,104.12
HPV Testing	43,580,902.24		−40,009,202	4988	−8020

Table 6. Cost-effectiveness analysis of HPV genotype test screening approach in terms of surrogate endpoint related to sensitivity of testing.

Alternatives	Cost (euro)	Number of women tested positive for HPV	ΔC (euro)	ΔE	ICER
PAP testing	8,173,199.85	35,387
HPV testing	43,451,513.10	62,191	35,278,313.25	26,804.40	1316

Table 7. Cost-benefit analysis.

	2024	2025	2026	2027	2028	AVG/year (euro)
Cost of HPV testing (euro)	13,510,504	13,563,595	13,595,383	13,607,323	13,600,797
Cost of colposcopy (euro)	1,432,689	1,399,638	1,368,462	1,339,112	1,311,540
Total cost of dual-stain triage testing p16/Ki67 cost of CINTec triage testing (euro)	1,487,483	1,431,193	1,377,008	1,324,851	1,274,647
Productivity loss	29,163,741	28,177,527	27,224,664	26,304,023	25,414,515
Total direct cost (euro)	16,430,676	16,394,425	16,340,853	16,271,287	16,186,984	16,324,845
Total direct + indirect costs (euro)	45,594,417	44,571,952	43,565,517	42,575,310	41,601,499	43,581,739
Benefits
LYG due to early testing and reduced mortality (euro)	51,529,984	51,529,984	51,529,984	51,529,984	51,529,984	51,529,984
Benefit/cost ratio payer perspective						3.16
Net present value payer perspective						35,205,139
Benefit/cost ratio societal perspective						1.18
Net present value societal perspective						7,948,245

Figure 1. Tornado diagram based on results of benefit/cost ratio.

Figure 2. Tornado diagram varying the main ICER parameters.

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Data availability statement

The raw data supporting the conclusions of this article is available upon request from the corresponding author.