Health impact and cost effectiveness of implementing gender-neutral HPV vaccination in Japan

Figures & data

Figure 1. Base-case estimated incidence per 100,000 person-years of A) cervical cancer, B) all other cancers (female), and C) all cancers (male) associated with human papillomavirus strains covered by the nonavalent vaccine.

‘Male’ and ‘female’ refer to sex assigned at birth. FOV, female-only vaccination with coverage rates of 30% among the primary cohort and 15% among the catch-up cohort; GNV, gender-neutral vaccination with coverage rates of 30% among the primary female cohort and 15% among the female catch-up and male cohorts.

Figure 2. Base-case estimated incidence per 100,000 person-years of A) anogenital warts (female), B) anogenital warts (male), C) Juvenile-Onset recurrent respiratory papillomatosis (female), and D) Juvenile-Onset recurrent respiratory papillomatosis (male) associated with human papillomavirus strains covered by the nonavalent vaccine.

‘Male’ and ‘female’ refer to sex assigned at birth. FOV, female-only vaccination with coverage rates of 30% among the primary cohort and 15% among the catch-up cohort; GNV, gender-neutral vaccination with coverage rates of 30% among the primary female cohort and 15% among the female catch-up and male cohorts.

Table 1. Cases and deaths averted in the base-case analysis for gender-neutral instead of female-only human papillomavirus vaccination strategies over 100 years in Japan.

Disease	Female		Male
	Cases	Deaths	Cases	Deaths
CIN1	28,094	NA	NA	NA
CIN2–3	94,390	NA	NA	NA
Cancers	17,228	1,892	6,033	1,849
Anal	790	97	1,324	183
Cervical	15,695	1,579	NA	NA
Oropharyngeal	509	12	4,508	1,631
Penile	NA	NA	201	36
Vaginal	143	40	NA	NA
Vulvar	92	15	NA	NA
AGW	170,219	NA	460,953	NA
RRP	266	161	382	17

AGW, anogenital warts; CIN, cervical intraepithelial neoplasia; NA, not applicable; RRP, recurrent respiratory papillomatosis.

Outcomes are for diseases associated with strains of human papillomavirus covered by the nonavalent vaccine. ‘Male’ and ‘female’ refer to sex assigned at birth.

Table 2. Base-case health care costs and quality-adjusted life years lost for gender-neutral versus female-only vaccination strategies over 100 years in Japan.

Item	Cost per capita (¥)		QALYs lost per capita
	FOV	GNV	FOV	GNV
HPV vaccination	3,887.91 ($29.57)	5,795.64 ($44.07)	NA	NA
Cervical cancer screening	21,975.89 ($167.11)	21,971.61 ($167.11)	NA	NA
Anal cancer	176.33 ($1.34)	171.99 ($1.31)	0.0010485582	0.0010325525
Cervical disease (cancer and CIN)	9,091.99 ($69.14)	8,954.31 ($68.09)	0.0261770821	0.0259891589
CIN due to HPV6/11	19.91 ($0.15)	18.58 ($0.14)	0.0000123278	0.0000115120
Oropharyngeal cancer	1,650.24 ($12.54)	1,618.53 ($12.31)	0.0039924571	0.0039433097
Penile cancer	21.52 ($0.16)	21.17 ($0.16)	0.0001220768	0.0001207610
Vaginal cancer	77.22 ($0.59)	76.83 ($0.58)	0.0003962989	0.0003950789
Vulvar cancer	34.06 ($0.26)	33.85 ($0.26)	0.0001592847	0.0001586663
Anogenital warts	262.61 ($2.00)	237.04 ($1.80)	0.0010183709	0.0009194198
RRP	25.15 ($0.19)	23.21 ($0.18)	0.0001234042	0.0001201887
Total	37,222.84 ($283.06)	38,922.75 ($295.99)	0.0330498607	0.0326906479
Difference, GNV versus FOV	NA	+1,699.91 (+$12.93)	NA	–0.0003592128

CIN, cervical intraepithelial neoplasia; FOV, female-only vaccination; GNV, gender-neutral vaccination; HPV, human papillomavirus; NA, not applicable; QALY, quality-adjusted life year; RRP, recurrent respiratory papillomatosis.

Figure 3. Tornado diagram illustrating how varying key model parameters affects the incremental cost-effectiveness ratio in the base case.

ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life years.

Table 3. One-way sensitivity analyses to determine how key model parameters affect the incremental cost-effectiveness ratio of gender-neutral versus female-only vaccination over 100 years in the base case.

Parameter varied	ICER (¥ / QALY gained)
	Minimum	Maximum
Discount rate, 0–5%	2,444,155.77 ($18,586.74)	13,119,041.93 ($99,764.57)
Disease disutility, ±20%	2,487,398.75 ($18,915.58)	11,575,375.47 ($88025.67)
No disutility among cancer survivors	4,732,328.94 ($35,987.29)	7,352,291.43 ($55,910.96)
Utility among the healthy population, ±20%	4,270,333.96 ($32,474.02)	5,915,411.24 ($44984.12)
Vaccine price, ±20%	3,922,537.38 ($29829.18)	5,542,120.50 ($42145.40)
Treatment cost, ±20%	4,616,618.25 ($35107.36)	4,848,034.70 ($36867.18)
20-year duration of vaccination protection	4,732,328.94 ($35987.29)	7,072,172.24 ($53780.78)
10 calibrated parameter combinations	4,282,133.32 ($32563.75)	5,069,389.28 ($38550.49)

ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life year.

The sensitivity analysis for each variable was conducted independently, with all other variables set to their base-case values.

Table 4. Public health and cost-effectiveness outcomes for gender-neutral versus female-only human papillomavirus vaccination strategies over 100 years in scenario analyses with varying female, catch-up, and male vaccination coverage rates.

VCR: female/ catch-up/male (%)	CIN1	CIN2–3	Cancer cases		AGW cases		RRP cases		Deaths		GNV versus FOV
	F	F	F	M	F	M	F	M	F	M	Additional net cost (¥) (US$)	QALYs gained	ICER (¥/QALY gained) (US$)
30 / 0 / 15	28,481	95,869	17,567	6,122	171,012	462,645	267	383	1,945	1,892	1,695.75 ($12.90)	0.0003662852	4,629,589.18 ($35,206.00)
30 / 0 / 30	54,999	184,427	33,853	11,609	335,744	878,030	522	749	3,761	3,612	3,406.38 ($25.90)	0.0007077956	4,812,659.07 ($36,598.17)
30 / 10 / 15	28,254	95,002	17,369	6,070	170,548	461,657	266	382	1,921	1,877	1,698.19 ($12.91)	0.0003621313	4,689,441.60 ($35,661.15)
30 / 10 / 30	54,542	182,683	33,458	11,508	334,820	875,994	520	747	3,714	3,079	3,411.24 ($25.94)	0.0006995569	4,876,291.05 ($37,082.06)
30 / 15 / 15 (base case)	28,094	94,390	17,228	6,033	170,219	460,953	266	382	2,053	1,866	1,699.91 ($12.93)	0.0003592128	4,732,320.23 ($35,987.23)
30 / 15 / 30	54,220	181,453	33,179	11,438	334,165	874,546	520	746	3,680	3,562	3,414.66 ($25.97)	0.0006937706	4,921,886.28 ($37,428.79)
30 / 30 / 15	27,453	91,929	16,665	5,890	168,890	458,090	264	379	1,837	1,825	1,706.78 ($12.98)	0.0003475430	4,910,980.54 ($37,345.86)
30 / 30 / 30	52,932	176,511	32,060	11,163	331,517	868,661	516	741	3,546	3,481	3,428.28 ($26.07)	0.0006706536	5,111,852.74 ($38,873.41)
50 / 0 / 25	22,759	72,546	14,264	7,718	165,205	488,988	272	390	1,675	2,430	2,961.44 ($22.52)	0.0003734569	7,929,805.68 ($60,302.71)
50 / 16.7 / 25	22,259	70,738	13,875	7,597	163,585	485,084	270	387	1,627	2,394	2,966.62 ($22.56)	0.0003644855	8,139,201.04 ($61,895.06)
50 / 25 / 25	21,908	69,467	13,601	7,514	162,430	482,281	268	385	1,594	2,369	2,970.25 ($22.59)	0.0003581819	8,292,579.74 ($63,061.44)
50 / 50 / 25	20,609	64,751	12,583	7,203	157,977	471,328	263	378	1,471	2,275	2,983.69 ($22.69)	0.0003347306	8,913,707.96 ($67,784.85)
70 / 0 / 35	11,615	38,904	8,585	8,042	62,380	219,942	107	154	1,089	2,565	4,271.36 ($32.48)	0.0002831090	15,087,330.24 ($114,732.55)
70 / 23.3 / 35	10,920	36,632	8,102	7,843	58,713	209,435	101	146	1,028	2,503	4,278.84 ($32.54)	0.0002694298	15,881,102.86 ($120,768.84)
70 / 35 / 35	10,444	35,076	7,769	7,705	56,152	202,006	98	141	986	2,461	4,283.99 ($32.58)	0.0002599706	16,478,746.04 ($125,313.66)
70 / 70 / 35	8,805	29,731	6,619	7,216	46,899	174,468	84	121	841	2,308	4,301.88 ($32.71)	0.0002267509	18,971,831.64 ($144,272.48)

AGW, anogenital warts; CIN, cervical intraepithelial neoplasia; F, female; FOV, female-only vaccination; GNV, gender-neutral vaccination; ICER, incremental cost-effectiveness ratio; M, male; QALY, quality-adjusted life year; RRP, recurrent respiratory papillomatosis; VCR, vaccination coverage rate.

Outcomes are for diseases associated with strains of human papillomavirus covered by the nonavalent vaccine. ‘Male’ and ‘female’ refer to sex assigned at birth. Values for costs and QALYs are per capita.