Extended surveillance to assess safety of 9-valent human papillomavirus vaccine

Figures & data

Table 1. Criteria for determining adverse events.

Adverse event	Medical setting	Post-vaccination risk period	First episode in which period?
GBS^a	Outpatient, inpatient, emergency department	1–42 days	First in 42 days
CIDP^b	Outpatient, inpatient, emergency department	1–180 days	First ever
Stroke	Inpatient, emergency department	0–42 days	First in 42 days

^aGuillain-Barré syndrome.

^bChronic inflammatory demyelinating polyneuropathy.

Table 2. Comparison of events after 9vHPV vaccine and after comparator vaccine populations in the Vaccine Safety Datalink, from October 4, 2015 (9vhpv vaccine) or January 1, 2007 (comparator vaccines) to January 2, 2021 (both 9vhpv and comparator vaccines).

Adverse event	Sex/age category^a	Number of 9vHPV doses	Number of events in the post-9vHPV risk period	Events in the post-9vHPV risk period per 100,000 9vHPV doses	Number of comparator vaccine doses	Number of events in the post-comparator vaccine risk period	Events in the post-comparator vaccine risk period per 100,000 comparator vaccine doses
GBS^b	F 9–17 years	680,795	3	0.4	1,029,301	7	0.7
	F 18–26 years	287,775	0	0	824,030	8	1.0
	M 9–17 years	726,585	3	0.4	1,341,127	10	0.8
	M 18–26 years	140,634	0	0	619,551	7	1.1
	Overall	1,835,789	6	0.3	3,814,009	32	0.8
CIDP^c	F 9–17 years	680,795	1	0.2	1,029,301	1	0.1
	F 18–26 years	287,775	1	0.4	824,030	0	0
	M 9–17 years	726,585	0	0	1,341,127	0	0
	M 18–26 years	140,634	0	0	619,551	1	0.2
	Overall	1,835,789	2	0.1	3,814,009	2	0.1
Stroke	F 9–17 years	680,795	4	0.6	1,029,301	7	0.7
	F 18–26 years	287,775	14	4.9	824,030	30	3.6
	M 9–17 years	726,585	1	0.1	1,341,127	15	1.1
	M 18–26 years	140,634	3	2.1	619,551	26	4.2
	Overall	1,835,789	22	1.2	3,814,009	78	2.1

^aF: Females. M: Males.

^bGuillain-Barré syndrome.

^cChronic inflammatory demyelinating polyneuropathy.

Table 3. Comparison of events after 9vHPV vaccine and after comparator vaccine populations in the Vaccine Safety Datalink, stratified by age and sex, from October 4, 2015 (9vHPV vaccine) or January 1, 2007 (comparator vaccines) to January 2, 2021 (both 9vHPV and comparator vaccines).

Adverse event	Sex/age category^a	Number of 9vHPV doses	Number of events in the post-9vHPV risk period	Number of comparator vaccine doses	Number of events in the post-comparator vaccine risk period	Ratio of cases after 9vHPV to cases after comparator vaccine (exact 95% CI)^b	1-sided p-value for Fisher’s exact test	Number of events in the post-9vHPV risk period needed to signal^c
GBS^d	F 9–17 years	680,795	3	1,029,301	7	0.7 (0.1, 2.8)	0.8	12
	F 18–26 years	287,775	0	824,030	8	0 (–)	1.0	8
	M 9–17 years	726,585	3	1,341,127	10	0.6 (0.1, 2.2)	0.9	12
	M 18–26 years	140,634	0	619,551	7	0 (–)	1.0	6
	Overall	1,835,789	6	3,814,009	32	0.4 (0.1, 0.9)	1.0	25
CIDP^e	F 9–17 years	680,795	1	1,029,301	1	1.5 (0.0, 118.7)	0.6	5
	F 18–26 years	287,775	1	824,030	0	–	0.3	3
	M 9–17 years	726,585	0	1,341,127	0	–	–	–
	M 18–26 years	140,634	0	619,551	1	0 (–)	1.0	3
	Overall	1,835,789	2	3,814,009	2	2.1 (0.2, 28.7)	0.4	5
Stroke	F 9–17 years	680,795	4	1,029,301	7	0.9 (0.2, 3.4)	0.7	12
	F 18–26 years	287,775	14	824,030	30	1.3 (0.7, 2.6)	0.2	19
	M 9–17 years	726,585	1	1,341,127	15	0.1 (0.0, 0.8)	1.0	16
	M 18–26 years	140,634	3	619,551	26	0.5 (0.1, 1.7)	0.9	12
	Overall	1,835,789	22	3,814,009	78	0.6 (0.4, 1.0)	1.0	52

^aF: Females. M: Males.

^bCalculated as “cases per 100,000 doses” for both 9vHPV vaccines and comparator vaccines.

^cNumber of cases needed to signal calculated by fixing the number of 9vHPV vaccine doses, the number of comparator vaccine doses, and the number of events occurring after comparator vaccine doses. The number of events occurring after 9vHPV vaccine doses was then artificially set to 0 and increased incrementally until a 1-sided Fisher’s exact test yielded a p-value < 0.05.

^dGuillain-Barré syndrome.

^eChronic inflammatory demyelinating polyneuropathy.