Public health impact and cost-effectiveness of switching from bivalent to nonavalent vaccine for human papillomavirus in Norway: incorporating the full health impact of all HPV-related diseases

Figures & data

Table 2. Deaths averted by nonavalent vaccination over 100 years.

	Number of deaths under each vaccination strategy				Deaths averted by nonavalent vaccination
	2vHPV	2vHPV with low XP	2vHPV with high XP	9vHPV	9vHPV vs. 2vHPV	9vHPV vs. 2vHPV with low XP	9vHPV vs. 2vHPV with high XP
Total deaths	5,941	5,453	5,443	4,897	1,044	556	546
Deaths in females – all	4,704	4,216	4,206	3,834	870	382	372
Cervical cancer^a	2,093	1,823	1,816	1,744	349	80	73
Vaginal cancer^a	1,602	1,395	1,392	1,217	386	178	175
Vulvar cancer^a	453	442	442	401	52	41	41
Anal cancer	325	325	325	289	36	36	36
Head and neck cancer	154	154	154	121	33	33	33
RRP	77	77	77	63	14	14	14
Deaths in males – all	1,237	1,237	1,237	1,063	174	174	174
Penile cancer	402	402	402	378	24	24	24
Anal cancer	171	171	171	161	10	10	10
Head and neck cancer	580	580	580	451	129	129	129
RRP	84	84	84	73	11	11	11

Abbreviations. HPV, human papillomavirus; RRP, recurrent respiratory papillomatosis; XP, cross-protection.

^aIndicates the types of cancer affected by cross-protection, giving rise to different numbers of averted deaths in different scenarios.

Figure 1. Flow chart for cervical cancer screening via HPV DNA testing. Abbreviation. hrHPV, high risk HPV genotypes

Table 5. Cost-effectiveness of nonavalent vaccination over 100 years.

	Cost/person (NOK)	QALY/person (years)	ICER (NOK/QALY)^a	ICER (EUR/QALY)^b
Base case
2vHPV	1,749	37.1807	102,500	€10,086
2vHPV with low XP	1,737	37.1811	140,789	€13,853
2vHPV with high XP	1,737	37.1812	141,720	€13,945
9vHPV	1,792	37.1826
Sensitivity analyses
4% Discounting
2vHPV	1,443	21.3407	164,224	€16,160
2vHPV with low XP	1,437	21.3409	200,241	€19,704
2vHPV with high XP	1,435	21.3409	210,666	€20,730
9vHPV	1,617	21.3418
Undiscounted
2vHPV	5,234	85.4079	55,158	€5,428
2vHPV with low XP	5,174	85.4103	85,807	€8,443
2vHPV with high XP	5,163	85.4108	95,021	€9,350
9vHPV	5,717	85.4167

Abbreviations. EUR, euros; HPV, human papillomavirus; ICER, incremental cost-effectiveness ratio; NOK, Norwegian krone; QALY, quality-adjusted life year; XP, cross-protection.

^aExpressed as the ICER of nonavalent vaccination vs. each respective bivalent vaccination strategy; ^bconversion rate 1 NOK = €0.0984.

Table 1. Cases averted by nonavalent vaccination over 100 years.

	Number of cases under each vaccination strategy				Cases averted by nonavalent vaccination
	2vHPV	2vHPV with low XP	2vHPV with high XP	9vHPV	9vHPV vs. 2vHPV	9vHPV vs. 2vHPV with low XP	9vHPV vs. 2vHPV with high XP
Cancer – all	25,078	23,644	23,617	20,721	4,357	2,923	2,896
Female cancers – all	16,546	15,112	15,084	13,606	2,940	1,506	1,478
Cervical cancer^a	5,266	4,512	4,494	4,290	975	221	203
Noncervical cancer	11,280	10,600	10,591	9,315	1,965	1,285	1,275
Anal cancer	3,302	3,302	3,302	3,062	241	241	241
Vaginal cancer^a	4,399	3,792	3,783	3,272	1,127	520	511
Vulvar cancer^a	2,528	2,455	2,455	2,184	344	271	271
Head and neck cancer	1,051	1,051	1,051	798	253	253	253
Male cancers – all	8,532	8,532	8,532	7,115	1,417	1,417	1,417
Anal cancer	1,665	1,665	1,665	1,565	100	100	100
Head and neck cancer	4,962	4,962	4,962	3,773	1,189	1,189	1,189
Penile cancer	1,906	1,906	1,906	1,777	129	129	129
Genital warts – all^b	2,614,756	2,614,756	2,614,756	2,192,831	421,925	421,925	421,925
Female	1,412,649	1,412,649	1,412,649	1,149,448	263,201	263,201	263,201
Male	1,202,107	1,202,107	1,202,107	1,043,382	158,725	158,725	158,725
RRP – all	3,386	3,386	3,386	2,843	543	543	543
Female	1,613	1,613	1,613	1,313	299	299	299
Male	1,773	1,773	1,773	1,529	244	244	244
Juvenile-onset	1,687	1,687	1,687	1,260	427	427	427
Adult-onset	1,699	1,699	1,699	1,583	116	116	116

Abbreviations. HPV, human papillomavirus; RRP, recurrent respiratory papillomatosis; XP, cross-protection.

^a Indicates the types of cancer affected by cross-protection, giving rise to different numbers of averted cases in different scenarios; ^bsome totals do not equal the sum of the subtotals due to rounding.

Figure 2. Incidence of cervical cancer attributable to nonavalent vaccine types over 100 years. Abbreviations. HPV, human papillomavirus; XP, cross-protection The 2vHPV low and high XP curves are superimposed because they have the same effect on cervical cancer.

Figure 3. Incidence of noncervical cancers attributable to nonavalent vaccine types over 100 years.Abbreviations. HPV, human papillomavirus; XP, cross-protection. In panel A, the 2vHPV low and high XP curves are superimposed because they have the same effect on noncervical cancer in females. In panel B, the 2vHPV, 2vHPV low XP, and high XP curves are superimposed because they have the same effect on cancer in males.

Figure 4. Incidence of HPV6/11-attributable genital warts and recurrent respiratory papillomatosis over 100 years. Abbreviations. HPV, human papillomavirus; RRP, recurrent respiratory papillomatosis 2vHPV is shown without cross-protection.

Table 3. Total costs associated with each vaccination strategy over 100 years.

	2vHPV	2vHPV with low XP	2vHPV with high XP	9vHPV
Total	9,429,813,572	9,364,175,356	9,362,916,208	10,472,266,375
Screening	1,053,760,967	1,053,760,967	1,053,760,967	1,053,760,967
Vaccine	2,655,905,959	2,655,905,959	2,655,905,959	4,392,568,287
Treatment	5,720,146,647	5,654,508,431	5,653,249,283	5,025,937,122
Cervical diseases (CIN & cancer)	407,575,903	363,084,099	362,115,581	350,783,390
Noncervical cancers	1,896,701,673	1,875,555,261	1,875,264,630	1,724,235,239
Vaginal cancers	259,667,125	240,878,889	240,604,427	224,882,689
Vulvar cancers	183,691,936	181,333,760	181,317,592	172,532,037
Anal cancers	543,755,817	543,755,817	543,755,817	528,557,615
Penile cancers	77,688,777	77,688,777	77,688,777	75,077,612
Head and neck cancers	831,898,016	831,898,016	831,898,016	723,185,286
Genital warts	2,474,705,104	2,474,705,104	2,474,705,104	2,142,255,773
RRP	941,163,967	941,163,967	941,163,967	808,662,720

Abbreviations: CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus; RRP, recurrent respiratory papillomatosis; XP, cross-protection.

All costs are in 2021 Norwegian krone (NOK).

Table 4. Treatment costs averted versus bivalent vaccination over 100 years.

	2vHPV with low XP	2vHPV with high XP	9vHPV
Total treatment costs	65,638,216 (100%)	66,897,364 (100%)	694,209,525 (100%)
Cervical diseases (CIN & cancer)	44,491,804 (68%)	45,460,322 (68%)	56,792,513 (8%)
Noncervical cancers	21,146,412 (32%)	21,437,043 (32%)	172,466,434 (25%)
Vaginal cancers	18,788,236	19,062,698	34,784,436
Vulvar cancers	2,358,176	2,374,344	11,159,899
Anal cancers	0	0	15,198,202
Penile cancers	0	0	2,611,165
Head and neck cancers	0	0	108,712,730
Genital warts	0	0	332,449,331 (48%)
RRP	0	0	132,501,247 (19%)

Abbreviations. CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus; RRP, recurrent respiratory papillomatosis; XP, cross-protection.

All costs are in 2021 Norwegian krone (NOK). Percentages of the total costs are given for the main cost categories (cervical diseases, noncervical cancers, genital warts, and RRP).

Figure 5. Sensitivity analysis of diseases included. Abbreviations. GW, genital warts; HPV, human papillomavirus; ICER, incremental cost-effectiveness ratio; NOK, Norwegian krone; QALY, quality-adjusted life year; RRP, recurrent respiratory papillomatosis; XP, cross-protection. Female-specific cancers are cervical, vaginal, and vulvar cancers.

Figure 6. Premium price analysis. Abbreviations. HPV, human papillomavirus; ICER, incremental cost-effectiveness ratio; NOK, Norwegian krone; QALY, quality-adjusted life year; XP, cross-protection The small dashed lines link the current (base case) price difference between the nonavalent and bivalent vaccines (554 NOK) to the corresponding ICERs. The large dashed line indicates the WTP threshold for low-severity diseases (275,000 NOK). The calculated data range from no price difference (0 NOK) to a price difference 70% higher than the base case (942 NOK).

Data availability

The authors confirm that the data supporting the findings of this study are available within the article and/or its supplementary materials.