Efficacy of the AS04-adjuvanted HPV-16/18 vaccine in young Chinese women with oncogenic HPV infection at baseline: post-hoc analysis of a randomized controlled trial

Figures & data

Figure 1. Plain language summary

Table 1. Summary of baseline demographic characteristics of women DNA-positive to at least one HR-HPV species at baseline in the TVC-E

	AS04-HPV-16/18 v cohort N = 444	Control cohort N = 427	Total N = 871
Age at first vaccination dose (years, Mean [SD])	23.2 (1.6)	22.8 (1.9)	23.0 (1.8)
Height (cm, mean [SD])	158.8 (5.4)	159.3 (5.3)	159.0 (5.4)
Weight (kg, mean [SD])	54.5 (8.4)	54.5 (8.6)	54.5 (8.5)
BMI (kg/m2, mean [SD])	21.6 (3.1)	21.5 (3.2)	21.5 (3.2)
Race (Chinese heritage, n [%])	473 (100)	451 (100)	924 (100)
Any 14 HR-HPV (n, [%]) (HPV-16/18/31/33/35/39/45/51/52/56/58/59/66/68)	444 (100)	427 (100)	871 (100)
Any 12 HR-HPV^a (n, [%]) (HPV-31/33/35/39/45/51/52/56/58/59/66/68)	316 (71.2)	314 (73.5)	630 (72.3)
HPV-16/18/31/33/45(n, [%])	190 (42.8)	166 (38.9)	356 (40.9)
Any non-HPV-16 A9 HR-HPV^b (n, [%])	191 (43.0)	185 (43.3)	376 (43.2)
Any non-HPV-18 A7 HR-HPV^c (n, [%])	92 (20.7)	78 (18.3)	170 (19.5)
HPV-16 and/or HPV-18 (n, [%])	128 (28.8)	113 (26.5)	241 (27.7)
HPV-16 and HPV-18 (n, [%])	4 (0.9)	7 (1.6)	11 (1.3)
HPV-16 (n, [%])	100 (22.5)	88 (20.6)	188 (21.6)
HPV-18 (n, [%])	32 (7.2)	32 (7.5)	64 (7.3)
HPV-31 (n, [%])	29 (6.5)	25 (5.9)	54 (6.2)
HPV-33 (n, [%])	33 (7.4)	24 (5.6)	57 (6.5)
HPV-45 (n, [%])	19 (4.3)	13 (3.0)	32 (3.7)
HPV-39 (n, [%]) HPV-45 (n, [%]) HPV-51 (n, [%]) HPV-52 (n, [%]) HPV-56 (n, [%]) HPV-58 (n, [%]) HPV-59 (n, [%]) HPV-66 (n, [%]) HPV-68 (n, [%])	46 (10.4) 19 (4.3) 42 (9.5) 109 (24.5) 31 (7.0) 40 (9.0) 6 (1.4) 28 (6.3) 29 (6.5)	33 (7.7) 13 (3.0) 55 (12.9) 123 (28.8) 34 (8.0) 42 (9.8) 16 (3.7) 47 (11.0) 25 (5.9)	79 (9.1) 32 (3.7) 97 (11.1) 232 (26.6) 65 (7.5) 82 (9.4) 22 (2.5) 75 (8.6) 54 (6.2)

^aExcluding coinfections with HPV-16/18.

^bExcluding coinfections with HPV-16

^cExcluding coinfections with HPV-18

AS04-HPV-16/18 v, AS04-adjuvanted HPV-16/18 vaccine; BMI, body mass index; Control, placebo containing Al(OH)₃; HPV, human papillomavirus; HR-HPV, high-risk human papillomavirus; N, total number of subjects; n (%), number (percentage) of subjects reporting at least one event; SD, standard deviation; TVC-E, total vaccinated cohort for efficacy.

Figure 2. Analysis flowchart

This post-hoc analysis focused on women with existing HR-HPV infection (DNA-positive) at baseline, irrespective of serostatus. For VE against individual HPV type, subjects were DNA-negative to the corresponding HPV type at baseline. For VE against combined types, subjects were DNA-negative to at least one HPV type at baseline (subjects were in the analysis of at least one single type). Besides meeting the above criteria for baseline status, subjects included in the relevant analyses must have sample available after vaccine dose 1 for the evaluation of the virological endpoints, including incident, 6-month and 12-month HPV persistent infections.¹High-grade cytology included squamous cells cannot exclude high-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, atypical glandular cells, or malignancy²VE against incident, 6-month and 12-month persistent infections associated with HPV-16, HPV-18 and HPV-16 and/or HPV-18 was assessed.³VE against incident, 6-month and 12-month persistent infections associated with HPV-31, HPV-33, HPV-45, and HPV-31 and/or HPV-33 and/or HPV-45 was assessed.⁴VE against incident, 6-month and 12-month persistent infections only associated with HPV-16 were assessed.⁵VE against incident, 6-month and 12-month persistent infections only associated with HPV-18 were assessed. HR-HPV, high-risk human papillomavirus; N, number of subjects; VE: vaccine efficacy.

Table 2. Vaccine efficacy against HPV-16/18 infection^a stratified by baseline DNA infection status (TVC-E)

VE against		Group	N	n	VE %, (95% CI)	P-value
Women DNA-positive to any of 14 HR-HPV species (HPV-16/18/31/33/35/39/45/51/52/56/58/59/66/68) at Month 0
Incident infection with:	HPV-16/18	AS04-HPV-16/18 v	429	13	74.7 (52.2 to 87.5)	<0.0001
		Control	408	45
	HPV-16	AS04-HPV-16/18 v	336	8	68.6 (27.8 to 87.8)	0.0034
		Control	329	24
	HPV-18	AS04-HPV-16/18 v	401	5	81.2 (49.7 to 94.4)	0.0002
		Control	385	24
6-month persistent infection with:	HPV-16/18	AS04-HPV-16/18 v	416	0	100 (79.8 to 100)	<0.0001
		Control	389	18
	HPV-16	AS04-HPV-16/18 v	327	0	100 (57.9 to 100)	0.0007
		Control	311	10
	HPV-18	AS04-HPV-16/18 v	388	0	100 (46.5 to 100)	0.0030
		Control	367	8
12-month persistent infection with:	HPV-16/18	AS04-HPV-16/18 v	408	0	100 (47.2 to 100)	0.0028
		Control	378	8
	HPV-16	AS04-HPV-16/18 v	321	0	100 (−44.2 to 100)	0.0550
		Control	303	4
	HPV-18	AS04-HPV-16/18 v	381	0	100 (−39.1 to 100)	0.0540
		Control	356	4
Women DNA-positive to HPV-16/18^b at Month 0
Incident infection with^c:	HPV-16/18	AS04-HPV-16/18 v	121	4	66.8 (−18.9 to 92.5)	0.0921
		Control	102	9
	HPV-16	AS04-HPV-16/18 v	28	1	61.2 (−646.2 to 99.3)	0.5825
		Control	23	2
	HPV-18	AS04-HPV-16/18 v	93	3	68.4 (−38.5 to 94.7)	0.1894
		Control	79	7
Women DNA-positive to any other 12 HR-HPV species (HPV-31/33/35/39/45/51/52/56/58/59/66/68) at Month 0
Incident infection with:	HPV-16/18	AS04-HPV-16/18 v	350	9	79.5 (57.2 to 91.3)	<0.0001
		Control	351	41
	HPV-16	AS04-HPV-16/18 v	314	7	70.5 (29.0 to 89.3)	0.0043
		Control	317	23
	HPV-18	AS04-HPV-16/18 v	344	2	91.0 (63.2 to 99.0)	<0.0001
		Control	340	21
6-month persistent infection with:	HPV-16/18	AS04-HPV-16/18 v	338	0	100 (75.4 to 100)	<0.0001
		Control	333	16
	HPV-16	AS04-HPV-16/18 v	305	0	100 (56.6 to 100)	0.0008
		Control	299	10
	HPV-18	AS04-HPV-16/18 v	332	0	100 (18.7 to 100)	0.0140
		Control	323	6
12-month persistent infection with:	HPV-16/18	AS04-HPV-16/18 v	332	0	100 (33.1 to 100)	0.0070
		Control	325	7
	HPV-16	AS04-HPV-16/18 v	300	0	100 (−48.4 to 100)	0.0582
		Control	291	4
	HPV-18	AS04-HPV-16/18 v	326	0	100 (−133.2 to 100)	0.1181
		Control	315	3
Women DNA-negative to HPV-16 and DNA-positive to any non-HPV-16 A9 types (HPV-31/33/35/52/58) at Month 0
Incident infection with	HPV-16	AS04-HPV-16/18 v	185	4	69.9 (0.6 to 92.9)	0.0409
		Control	178	12
6-month persistent infection with:		AS04-HPV-16/18 v	179	0	100 (0.8 to 100)	0.0258
		Control	168	5
12-month persistent infection with:		AS04-HPV-16/18 v	176	0	100 (−119.6 to 100)	0.1090
		Control	162	3
Women DNA-negative to HPV-18 and DNA-positive to any non-HPV-18 A7 types (HPV-39/45/59/68) at Month 0
Incident infection with	HPV-18	AS04-HPV-16/18 v	92	0	100 (45.3 to 100)	0.0037
		Control	78	7
6-month persistent infection with:		AS04-HPV-16/18 v	91	0	100 (−3,137.4 to 100)	0.4518
		Control	75	1
12-month persistent infection with:		AS04-HPV-16/18 v	89	0	-	-
		Control	71	0

^aIndividual and combined vaccine efficacy against infections with HPV-16 and HPV-18 in women DNA-negative to the considered HPV type at baseline, using conditional exact method. For individual type, subjects were DNA-negative to the corresponding HPV type at Month 0. For combined types, subjects were DNA-negative to at least one HPV type at Month 0 (subjects were in the analysis of at least one single type). Follow-up starts at day after dose 1.

^bHPV-16/18: subjects DNA-positive to either HPV-16 or HPV-18 at Month 0 and DNA-negative to the other type at Month 0. HPV-16: subjects DNA-positive to HPV-18 at Month 0 and DNA-negative to HPV-16 at Month 0. HPV-18: subjects DNA-positive to HPV-16 at Month 0 and DNA-negative to HPV-18 at Month 0.

^cthere were not enough cases to evaluate 6-month or 12-month persistent infection-related endpoints in women DNA-positive to HPV-16/18 at baseline.

AS04-HPV-16/18 v, AS04-adjuvanted HPV-16/18 vaccine; CI, confidence interval; HPV, human papillomavirus; HR-HPV, high-risk human papillomavirus; N, number of subjects included in each group; n, number of subjects reporting at least one event in each group; TVC-E, total vaccinated cohort for efficacy; VE, vaccine efficacy.

Table 3. Vaccine efficacy against HPV-31/33/45 infection^a stratified by baseline DNA infection status (TVC-E)

VE against		Group	N	n	VE %, (95% CI)	P-value
Women DNA-positive to any of 14 HR-HPV species (HPV-16/18/31/33/35/39/45/51/52/56/58/59/66/68) at Month 0
Incident infection with:	HPV-31/33/45	AS04-HPV-16/18 v	433	31	55.5 (30.3 to 72.1)	0.0006
		Control	415	61
	HPV-31	AS04-HPV-16/18 v	404	13	63.2 (28.0 to 82.3)	0.0032
		Control	391	32
	HPV-33	AS04-HPV-16/18 v	401	15	47.0 (−3.8 to 73.9)	0.0774
		Control	391	26
	HPV-45	AS04-HPV-16/18 v	414	8	53.5 (−15.2 to 82.8)	0.0985
		Control	402	16
6-month persistent infection with:	HPV-31/33/45	AS04-HPV-16/18 v	420	19	24.3 (−45.3 to 61.0)	0.4316
		Control	396	23
	HPV-31	AS04-HPV-16/18 v	393	6	49.8 (−48.0 to 84.8)	0.2234
		Control	374	11
	HPV-33	AS04-HPV-16/18 v	389	8	−7.8 (−249.1 to 65.9)	1.0000
		Control	373	7
	HPV-45	AS04-HPV-16/18 v	401	5	22.1 (−206.2 to 81.2)	0.7685
		Control	384	6
12-month persistent infection with:	HPV-31/33/45	AS04-HPV-16/18 v	412	9	25.0 (−99.1 to 72.5)	0.6521
		Control	384	11
	HPV-31	AS04-HPV-16/18 v	386	1	84.7 (−26.2 to 99.7)	0.0613
		Control	362	6
	HPV-33	AS04-HPV-16/18 v	382	5	−135.3 (−2,370.4 to 61.5)	0.4522
		Control	361	2
	HPV-45	AS04-HPV-16/18 v	393	3	6.6 (−597.6 to 87.5)	1.0000
		Control	374	3
Women DNA-positive to HPV-16/18 at Month 0
Incident infection with:	HPV-31/33/45	AS04-HPV-16/18 v	125	7	71.0 (27.3 to 89.8)	0.0099
		Control	109	18
	HPV-31	AS04-HPV-16/18 v	121	3	61.4 (−80.5 to 93.8)	0.3104
		Control	106	6
	HPV-33	AS04-HPV-16/18 v	118	3	70.0 (−24.9 to 94.9)	0.1219
		Control	107	8
	HPV-45	AS04-HPV-16/18 v	122	2	80.5 (2.2 to 98.0)	0.0488
		Control	108	8
6-month persistent infection with:	HPV-31/33/45	AS04-HPV-16/18 v	121	4	37.3 (−191.4 to 87.6)	0.7376
		Control	107	5
	HPV-31	AS04-HPV-16/18 v	119	0	100 (−2,921.7 to 100)	0.4664
		Control	104	1
	HPV-33	AS04-HPV-16/18 v	114	3	−25.4 (−1,401.1 to 85.6)	1.0000
		Control	105	2
	HPV-45	AS04-HPV-16/18 v	118	1	60.2 (−664.3 to 99.3)	0.6041
		Control	106	2
12-month persistent infection with:	HPV-31/33/45	AS04-HPV-16/18 v	118	4	−59.6 (−1,664 to 77.1)	0.6876
		Control	103	2
	HPV-31	AS04-HPV-16/18 v	116	0	100 (−2,910.6 to 100)	0.4630
		Control	100	1
	HPV-33	AS04-HPV-16/18 v	111	3	−150.4 (−13,044.8 to 79.9)	0.6231
		Control	101	1
	HPV-45	AS04-HPV-16/18 v	115	1	-	-
		Control	102	0

^aIndividual and combined vaccine efficacy against infections with HPV-31, HPV-33, and HPV-45 in women DNA-negative to the considered HPV type at baseline, using conditional exact method. For individual type, subjects were DNA-negative to the corresponding HPV type at Month 0. For combined types, subjects were DNA-negative to at least one HPV type at Month 0 (subjects were in the analysis of at least one single type). Follow-up starts at day after dose 1.

AS04-HPV-16/18 v, AS04-adjuvanted HPV-16/18 vaccine; CI, confidence interval; HPV, human papillomavirus; HR-HPV, high-risk human papillomavirus; N, number of subjects included in each group; n, number of subjects reporting at least one event in each group; TVC-E, total vaccinated cohort for efficacy; VE, vaccine efficacy

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