Estimating the epidemiological impact and cost-effectiveness profile of a nonavalent HPV vaccine in Spain

Figures & data

Table 1. Disease events and deaths related to HPV types 6/11/16,718/31/33/45/52/58 prevented over a time horizon of 100 years.

	4vHPV GIRLS vs 9vHPV GIRLS	4vHPV GIRLS vs 9vHPV GNV	9vHPV GIRLS vs 9vHPV GNV
CIN1 cases	48,507	55,595	7,088
CIN2/3 cases	111,090	132.496	21.406
Cervical cancer cases	15,295	18,665	3,369
Cervical cancer deaths	3,114	3,834	720
Vaginal cancer	0	31	31
Anal cancer cases
Females	45	195	151
Males	33	855	822
Vaginal cancer deaths	0	8	8
Anal cancer deaths
Females	13	57	45
Males	10	257	247
Genital warts cases
Females	0	197,194	197,194
Males	0	607,659	607,659

9vHPV, nonavalent vaccine; 4vHPV, quadrivalent vaccine; GNV, gender-neutral, vaccination, CIN, cervical intraepithelial neoplasia.

Table 2. Additional reductions in the incidence and mortality rates of diseases related to HPV types 6/11/16/18/31/33/45/52/58 over a time horizon of 100 years.

	4vHPV GIRLS vs 9vHPV GIRLS	4vHPV GIRLS vs 9vHPV GNV	9vHPV GIRLS vs 9vHPV GNV
CIN1 incidence	30.5%	35.0%	6.4%
CIN2/3 incidence	23.9%	28.5%	6.1%
Cervical cancer incidence	14.0%	17.1%	3.%
Cervical cancer mortality	11.4%	14.0%	3.0%
Vaginal cancer incidence	0.0%	2.5%	2.5%
Anal cancer incidence
Females	1.0%	4.4%	3.5%
Males	0.4%	11.2%	10.8%
Vaginal cancer mortality	0.0%	2.3%	2.3%
Anal cancer mortality
Females	0.9%	4.0%	3.1%
Males	0.4%	10.3%	9.9%
Genital warts incidence
Females	0.0%	29.2%	29.2%
Males	0.0%	44.3%	44.3%

9vHPV Girls, nonavalent vaccine in girls; 9vHPV GNV, nonavalent vaccine in girls and boys; 4vHPV Girls, quadrivalent vaccine in girls; CIN, cervical intraepithelial neoplasia.

Figure 1. Epidemiological impact of GNV vaccination strategies over a 100-year time horizon.

*Related to the HPV types included in the nonavalent vaccine (HPV types 6/11/16/18/31/33/45/52/58).

Table 3. Cost-effectiveness results in the base case analysis.

Comparison		9vHPV		Comparator
9vHPV	Comparator	Costs/ person (€)	QALYs/person	Costs/ person (€)	QALYs/ person	Incremental costs/person (€)	Incremental QALYs/ person	Cost per QALY (€/QALY)
Girls	4vHPV Girls	428.07	28,605.65	424.81	28,605.23	3.26	0.00042	7,718
Gender-neutral	4vHPV Girls	450.42	28,606.07	424.81	28,605.23	25.61	0.00084	30,426
Gender-neutral	9vHPV Girls	450.42	28,606.07	428.07	28,605.65	22.35	0.00042	53,244

QALY, Quality-Adjusted Life Year; 9vHPV Girls, nonavalent vaccine in girls; 9vHPV gender-neutral, nonavalent vaccine in girls and boys; 4vHPV Girls, quadrivalent vaccine in girls.

Figure 2. Tornado diagrams showing the ICERs obtained in the sensitivity analysis.

Table 4. Vaccine efficacy assumptions (International).

Vaccine assumptions	HPV16	HPV18	HPV TYPES 31, 33, 45, 52 and 58***
Cervical cancer
Vaccine efficacy for preventing cervical infections:
- Male*	0.411	0.621	0.411
- Female**	0.760	0.963	0.760
Degree of protection of the vaccine against cervical HPV types 16/18 infections becoming persistent	0.988	0.984	0.988
Degree of protection of the vaccine against HPV types 16/18 -related CIN	0.979	1	0.979
Vaginal and vulvar cancers
Vaccine efficacy for preventing vaginal/vulvar infections:
- Male*	0.411	0.621
- Female**	0.76	0.963
Degree of protection of the vaccine against vaginal/vulvar HPV types 16/18 infections becoming persistent	0.988	0.984
Degree of protection of the vaccine against HPV types 16/18-related VaIN/VIN	1	1
Anal, penile and H&N cancers
Vaccine efficacy for preventing anal/penile***/H&N infections
- Male*	0.411	0.621	0.621
- Female	0.760	0.963	0.963
Degree of protection of the vaccine against anal/penile/H&N infections becoming persistent
- Male*	0.787	0.960	0.960
- Female	0.988	0.984	0.984
Degree of protection of the vaccine against -related AIN/PIN/H&N neoplasia	0	0
Vaccine assumptions	HPV6	HPV11
Vaccine efficacy against HPV infection
- Males	0.490	0.570
- Females	0.761	0.761
Degree of protection of the vaccine against HPV-related genital warts
- Males	0.843	0.909
- Females	0.989	1
Degree of protection of the vaccine against HPV-related CIN1	1	1

*Preventing male genital infections through male vaccination is assumed to prevent transmission of genital infections to females.

**Preventing female genital infections through vaccination is assumed to prevent transmission of genital infections to males.

***Values are not from the primary source; we assumed that efficacy was the same as the quadrivalent vaccine on HPV types 16/18.

AIN: anal intraepithelial neoplasia; CIN: cervical intraepithelial neoplasia; H&N: head and neck; HPV: Human Papillomavirus; PIN, penile intraepithelial neoplasia; VaIN: vaginal intraepithelial neoplasia; VIN: vulvar intraepithelial neoplasia.

Sources:

Females, Elbasha et al. (2010)⁴⁰ and Joura et al. (2007)⁵³.

Males, Giuliano et al. (2011)⁵⁵.

Table 5. Costs of diagnosing and treating diseases caused by HPV infection.

Parameter	Sex	Original values	Inflated values (2017 € value)	Source
Costs per episode of care
CIN1	Female	€981	€1,090	Castellsague et al. (2009),^Citation60 Diaz et al. (2010),^Citation59 Morano et al. (2012)^Citation61
CIN2	Female	€1,434	€1,593
CIN3, CIS	Female	€1,739	€1,929
Cervical cancer, local disease*	Female	€9,156	€9,428	Georgalis et al. (2016)^Citation62
Cervical cancer, regional disease*	Female	€23,212	€23,902
Cervical cancer, distant disease*	Female	€34,044	€35,057
VaIN1	Female	€981	€1,061	Assumption**
VaIN2	Female	€2,868	€3,186
VaIN3	Female	€3,478	€3,856
Vaginal cancer	Female	€10,235	€11,398	Cortes et al. (2012)^Citation63
Vulvar cancer	Female	€12,470	€13,887	Cortes et al. (2012)^Citation63
Penile cancer	Male	€6,382	€7,082	Gil-Prieto et al. (2012)^Citation35***
Anal cancer	Male	€6,692	€7,626	Gil-Prieto et al. (2012)^Citation35***
Anal cancer	Female	€6,968	€7,941
Head and neck cancer****	Male	€7,216	€8,007	Gil-Prieto et al. (2012)^Citation36***
Head and neck cancer****	Female	€7,425	€8,239
Genital warts	Male	€1,056	€1,122	Castellsague et al. (2009)^Citation64
Genital warts	Female	€833	€885
RRP	Male; female	€24,492	€24,492	Hughes et al. (2011)^Citation65
Parameter	Value (2017 €)		Source
Costs of screening and diagnostic tests for cervical and vaginal cancers
Screening (cytology) and office visit	€88		Trapero-Bertran et al. (2017)^Citation66
Colposcopy	€29		Oblikue Rate Andalusia (2017)^Citation67
Biopsy	€90		Oblikue Rate Basque Country (2017)^Citation68

*Disease stages can be related to the International Federation of Gynecology and Obstetrics (FIGO) classification system as follows: “Local disease” corresponds to stages II, i.e. localized primary tumor and I; “Regional disease” corresponds to stage III, i.e. metastasis to regional lymph nodes; “Distant disease” corresponds to stage IV, i.e. distant metastatic disease.⁶⁹

**In the absence of cost data for VaIN, the cost of VaIN1 was assumed to be identical to that of CIN1, and based on cost estimates from Bergeron et al. (2006), a French study, those of VaIN2/3 were assumed to be twice as expensive as their CIN counterparts.⁴⁶

***Costs of penile, anal, and head and neck cancers correspond only to hospital costs because they were obtained from retrospective studies based on a Spanish database of hospital discharges.^35,36

****Used only in the sensitivity analysis.

CIN, cervical intraepithelial neoplasia; CIS, carcinoma in situ; HPV, human papillomavirus; RRP, recurrent respiratory papillomatosis; VaIN, vaginal intraepithelial neoplasia; VIN, vulvar intraepithelial neoplasia.

Table 6. Model calibration.*

	Overall incidence (per 100,000)
	Female		Male
Overall incidence of cancers and genital warts
CIN1	265.46		–
CIN2/3	137.36		–
Cervical cancer	8.6		–
Vaginal cancer	0.3		–
Vulvar cancer	1.12		–
Anal cancer	0.34		0.6
Oral cavity cancer	2.3		7.4
Oropharyngeal cancer	0.4		3.9
Laryngeal cancer	0.7		7.8
Head and neck cancer**	6.30		23.10
Penile cancer	–		1.09
Genital warts	99.59		136.58
	Overall mortality (per 100,000)
	Female		Male
Overall mortality by cancers
Cervical cancer	1.97		-
Vaginal cancer	0.1		-
Vulvar cancer	0.64		-
Anal cancer	0.1		0.19
Oral cavity cancer	1.0		2.98
Oropharyngeal cancer	0.16		0.97
Laryngeal cancer	0.23		4.3
Head and neck cancer	0.37		3.04
Penile cancer	-		0.36
		Genotypes included in 4vHPV		Genotypes included in 9vHPV
	Prevalence (% HPV+ cancers)	Female	Male	Female	Male
Proportion of cancers and diseases related to HPV, to HPV types 6/11/16/18, and to HPV types 6/11/16/18/31/33/45/52/58 by vaccine
CIN1	100%	24.0%	-	48.5%	-
CIN2/3	100%	45.5%	-	82.3%	-
Cervical cancer	100%	72.8%	-	89.0%	-
Vaginal cancer	71.1%	71.3%	-	85.2%	-
Vulvar cancer	19.3%	73.5%	-	84.0%	-
Anal cancer	87.6%	87.1%	87.1%	89.8%	89.8%
Oral cavity cancer	16.0%	100%	100%	100%	100%
Oropharyngeal cancer	28.2%	89.5%	89.5%	89.5%	89.5%
Laryngeal cancer	21.3%	86.2%	86.2%	86.2%	86.2%
Penile cancer	46.7%	-	73.6%	-	73.6%
Genital warts	100%	90.0%	90.0%	90.0%	90.0%

*Calibration was carried out in the population aged 15 to 85 years.

**Used only in the sensitivity analysis.

CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus.

Sources:

Cervical disease, Torné Bladé et al. (2014).¹⁹

Vaginal, vulvar, anal, cancer, H&N, and penile cancers, ICO (2016).²³

Genital warts, Castellsagué et al. (2009).⁶⁴

Oral, oropharyngeal, and laryngeal cancers, IARC (2012).⁷⁴

Overall mortality by cancers, INE.⁷⁵

Proportion of cancers and diseases related to HPV: Hartwig et al. (2012)⁷⁶ and Hartwig et al. (2015).³

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