Evaluation of optic neuritis following human papillomavirus vaccination

Figures & data

Figure 1. Chart validation.

Table 1. HPV vaccination doses and occurrence of potential ON in the self-controlled temporal scan statistic.

		Number of ON outcomes
HPV vaccination dose	Number of exposed	Total	1–60 days	61–120 days
First	434,906	33	20	13
Second	315,611	32	21	11
Third	185,523	15	8	7
Combined	434,906	80	49	31

Figure 2. Stacked Strip Plot for ON events after the first, second or third HPV vaccination.

Figure 3. Self-controlled temporal scan statistic.

Table 2. Association between HPV vaccination and occurrence of ON using temporal scan statistic.

	Primary analysis^*				Secondary analysis^†
Occurrence of ON	Cluster time frame	Number of cases in the cluster	Relative risk	P-value	Cluster time frame	Number of cases in the cluster	Relative risk	P-value
After the first dose	26–28	4	5.38	0.25	26–28	4	5.38	0.25
After the second dose	20–52	18	3.39	0.03	22–52	14	2.87	0.18
After the third dose	6–22	6	4.04	0.26	6–22	6	6.06	0.09
Combined analysis^‡	9–56	46	2.03	0.06	9–56	46	2.03	0.06

* Second dose is at least 60 days from the first dose; third dose is at least 180 days from the first dose

^† Second dose is at least 60 days and at most 180 days from the first dose; third dose is at least 180 days and at most 2 years from the first dose and at least 60 days after the second dose

^‡ Second dose is at least 60 days from the first dose; third dose is at least 180 days from the first dose and at least 60 days after the second dose

Figure 4. Matched cohort design.

Table 3. Baseline characteristics for HPV vaccinated patients and matched HPV unvaccinated patients.

		HPV vaccinated		Matched HPV unvaccinated
Characteristics		N	%	N	%	p-value
Total		327,918		327,918
History of other autoimmune diseases^*		5,774	1.76	3,966	1.21	<0.001
History of other vaccinations^†		327,918	100.00	169,186	51.59	<0.001
Enhanced Deyo-Charlson index		31,022	9.46	27,523	8.39	<0.001
Region^‡						<0.001
	Mid-West	88,635	27.03	82,216	25.07
	North East	84,396	25.74	81,814	24.95
	South	92,915	28.33	94,838	28.92
	West	61,944	18.89	69,050	21.06

* Includes autoimmune thyroid diseases, autoimmune demyelinating diseases, Rheumatologic/autoimmune diseases, and Type 1 diabetes in the one year prior to either HPV vaccination or well child visit.

^† Includes routine vaccination including poliovirus, pneumonia, flu, varicella, meningococcal, hepatitis A and B, MMR, DPT, rotavirus, hemophilus influenza, rabies in 90 days prior and 30 days post to either HPV vaccination or well child visit.

^‡ Region could not be determined for 28 patients

Table 4. Occurrence of potential ON in the HPV vaccinated and matched HPV unvaccinated groups in the 60 days following index date^* in the matched cohort design.

	HPV vaccinated		Matched HPV unvaccinated
HPV vaccination dose	N	%	N	%
First	16	0.005	16	0.005
Second	17	0.008	13	0.006
Third	3	0.003	3	0.003
Combined	36	0.006	32	0.005

* Index date is defined as the HPV vaccination date of each dose for the vaccinated group. For the matched unvaccinated group, index date is the closest routine vaccination or well child visit date corresponding to the first HPV vaccination date, or the date corresponding to the second or third HPV vaccination date as the corresponding matched vaccinated member.

Table 5. Association between HPV vaccination and occurrence of potential ON in the matched cohort design.

			First dose		Second dose		Combined
Type of analysis	Predictors		RR^*	p-value	RR^*	p-value	RR^*	p-value
Unadjusted	HPV vaccination		0.99 (0.50–1.99)	0.99	1.30 (0.63–2.68)	0.47	1.12 (0.70–1.80)	0.64
Adjusted	HPV vaccination		0.94 (0.39–2.24)	0.88	1.43 (0.62–3.28)	0.41	1.10 (0.62–1.96)	0.75
	History of other autoimmune diseases^†		36.02 (14.41–90.04)	<.0001	9.65 (2.67–34.87)	<0.01	16.84 (7.34–38.65)	<.0001
	History of other vaccinations^‡		0.79 (0.29–2.14)	0.65	1.07 (0.41–2.77)	0.89	0.86 (0.45–1.65)	0.64
	Enhanced Deyo-Charlson index		0.20 (0.04–1.00)	0.05	1.23 (0.38–3.95)	0.73	0.70 (0.28–1.77)	0.45
	Region
		Mid-West	1.21 (0.40–3.72)	0.73	2.72 (0.76–9.79)	0.13	1.49 (0.70–3.20)	0.30
		North East	1.93 (0.68–5.46)	0.22	1.69 (0.44–6.50)	0.44	1.61 (0.76–3.40)	0.21
		South	0.86 (0.26–2.78)	0.80	2.06 (0.56–7.62)	0.28	1.11 (0.51–2.44)	0.79

* RR-Relative Risk

^† Includes autoimmune thyroid diseases, autoimmune demyelinating diseases, Rheumatologic/autoimmune diseases, and Type 1 diabetes in the one year prior to either HPV vaccination or well child visit

^‡ Includes routine vaccination including poliovirus, pneumonia, flu, varicella, meningococcal, hepatitis A and B, MMR, DPT, rotavirus, hemophilus influenza, rabies in 90 days prior and 30 days post to either HPV vaccination or well child visit