Cost-effectiveness and epidemiological impact of gender-neutral HPV vaccination in Spain

Figures & data

Figure 1. Model structure (reprinted from HIQA, 2018)⁸.

Θ = annual probability of receiving HPV vaccine; λ = annual probability of getting infected with HPV; E = vaccine efficacy against HPV subtypes; k = sex; a = age; t = year.

Table 1. Relative risk (RR) of persistent HPV infection after vaccination.

HPV type	RR of persistent infection in females Media (95%CI)/Source		RR of persistent infection in males Media (95%CI)/Source
6/11	0.063 (0.006–0.270)	[17]	0.218 (0.095–0.430)	[18]
16	0.101 (0.026–0.271)	[17]	0.377 (0.242–0.561)	[18]
18	0.137 (0.012–0.582)	[17]	0.320 (0.165–0.570)	[18]
31/33/45/52/58	0.062 (0.038–0.095)	[19]	0.062 (0.038–0.095)	[19]

CI: Confidence interval; RR: relative risk.

Table 2. Cost data included in the HPV vaccination model.

Resource	€ 2020	Source
Vaccination costs
4-valent vaccine dose	29.16 [95%CI: 29.15–29.62]	Framework Agreement for the selection of vaccine suppliers, Ministry of Health
9-valent vaccine dose	45.00 [95%CI: 44.69–45.31]
Administration per dose	6.07 [95%CI: 5.30–6.96]	[21]
Costs of treatment of HPV-attributable diseases
CIN1	257.78 [95%CI: 212.44–314.52]	[22]
CIN2/3	1,517.08 [95%CI: 1,248.91–1,842.76]	[22]
Cervical cancer	13,212.64 [95%CI: 10,865.11–16,054.22]	[22]
Anal cancer	31,574.63 [95%CI: 25,811.72–38,531.63]	[23]
VIN or VaIN	1,517.08 [95%CI: 1,256.57–1,849.01]	[8]
Vaginal cancer	6,477.73 [95%CI: 13,625–74,363]	[8,24]
Vulvar cancer	6,496.46 [95%CI: 4,462.60–6,612.53]	[8,24]
Head & neck cancer	10,413.97 [95%CI: 8,316.27–10,556.33]	[8,25]
Penile cancer	9,365.50 [95%CI: 6,456.94–9,587.55]	[8,25]
RRP	1,594.49 [95%CI: 1,305.85–1,941.43]	[8]
Anogenital warts	1,063.10 [95%CI: 872.14–1,289.17]	[26]
Palliative care	11,472.03 [95%CI: 9,420.85–13,947.08]	[27]
Mild adverse event (5% of the affected)	45.38 [95%CI: 37.22–55.45] (GP visit) + 0.21 (treatment) [95%CI: 0.12–0.38]	Mean tariff of Spanish provinces; [8]
Serious adverse event	1,607.26 [95%CI: 1,319.88–1,949.93]	[8]

CIN: Cervical intraepithelial neoplasia; VIN: Vulvar intraepithelial neoplasia; VaIN: Vaginal intraepithelial neoplasia; RRP: Recurrent respiratory papillomatosis; GP: General practitioner.

Table 3. Costs and benefits of HPV vaccination strategies (in relation to vaccination of girls with the 4-valent vaccine). Strategies are sorted by QALYs.

Strategy	Costs (millions of €)	QALYs
No vaccine	890	-177,140
Girls-only 4-valent	0	0
Gender-neutral 4-valent	254	7,977
Girls-only 9-valent	-85	40,284
Gender-neutral 9-valent	299	51,565

QALY: Quality-adjusted life year.

Table 4. Incremental cost-effectiveness ratio (ICER) of the two most effective strategies.

Strategy	Costs (millions of €)*		QALYs*		ICER (€/QALY)
	Relative value	Incremental	Relative value	Incremental
Girls-only 9-valent	-85	-	40,284	-	-
Gender-neutral 9-valent	299	384	51,565	11,281	34,040 [95%CI: 13,625–74,363]

QALY: Quality-adjusted life year; ICER: Incremental cost-effectiveness ratio; CI: Confidence interval.

*Costs and benefits in relation to girls-only 4-valent strategy.

Figure 2. Cost-effectiveness plane of gender-neutral 9-valent strategy in relation to girls-only 9-valent strategy.

QALY = Quality-adjusted life year; WTP = Willingness-to-pay threshold.

Table 5. Cumulative number of cases averted after changing the HPV immunization strategy.

Disease avoided	Cumulative cases avoided relative to a girls-only 4-valent programme
	Girls-only 9-valent				Gender-neutral 9-valent
	10 y	20 y	30 y	10 y		20 y	30 y
Pre-cancerous lesions
CIN 1	920	79,616	258,168	1,732		92,288	293,549
CIN 2/3	341	22,531	65,981	746		26.882	77,382
VaIN 2/3	7	20	47	9		26	60
VIN 2/3	27	92	205	40		134	296
Invasive cancers
Cervical cancer	13	154	663	18		207	875.0
Anal cancer	0	0	2	0		2	15
Vaginal cancer	1	2	7	1		3	10
Vulvar cancer	0	5	24	0		7	34
Other
Anogenital warts	0	0	0	1,922		15,331	39,208

Cumulative cases compared to girls-only 4-valent strategy.

CIN = Cervical intraepithelial neoplasia; VIN = Vulvar intraepithelial neoplasia; VaIN = Vaginal intraepithelial neoplasia; y = years.

Figure 3. Tornado diagram of the scenario analyses for gender-neutral 9-valent strategy compared to girls-only 9-valent strategy.

WTP = willingness to pay threshold; ICER = incremental cost-effectiveness ratio; y = year.

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