5 - Observational Study of Routine Use of 9-Valent Human Papillomavirus Vaccine: Safe in More Than 140,000 Individuals

Background: Nine-valent human papillomavirus (HPV) vaccine (9vHPV vaccine, Gardasil®9) was licensed in the US in Dec-2014. Using a self-controlled risk interval design, we conducted a post-licensure retrospective cohort study within Kaiser Permanente in Northern California (KPNC) to assess 9vHPV safety following routine administration.

Methods: We included KPNC members 9-years or older who received 9vHPV as their first dose of HPV vaccine between Oct-2015 and Sep-2017. Post-vaccination emergency and hospitalization events were compared during risk intervals (days 1-60 and 0-14) with later self-comparison intervals using conditional logistic regression, following all 9vHPV vaccine doses combined, and by dose. We investigated significant findings by assessing post-vaccination timing and medical record reviews. We evaluated and reviewed medical records for all day 0 allergic reaction and syncope events, and all deaths during the study. An independent Safety Review Committee reviewed potential safety signals.

Results: We studied 140,628 9vHPV-vaccinated individuals, including 69,027 (49%) who received 2 doses and 29,901 (21%) 3 doses, totaling 239,556 doses. Eight categories were significantly increased in at least one analysis (Table). On review, most findings were previously known, preceded vaccination, or were better explained by other medical history. Some day 0 allergic reactions and syncope were potentially related to vaccination. None of the 20 deaths were considered related to 9vHPV.
Table. Elevated diagnosis categories comparing risk and self-comparison intervals.

Diagnosis Categories	ORs (95% CI)
Diabetes mellitus	1.66 (1.01, 2.74)
Delirium	NE (1.11, NE)
Nervous system disorders+2	1.33 (1.02, 1.72)
Digestive disorders+4	1.21 (1.03, 1.41)
Male genital disease	1.60 (1.04, 2.46)
Skin disorders+1	1.88 (1.00, 3.53)
Congenital anomalies, nervous system	5.01 (1.10, 22.83)
Symptoms, ill-defined+1	1.36 (1.13, 1.64)

⁺ⁿ indicates number of elevated sub-categories, for a total of 16 categories. NE: not estimable.

Conclusion: This large study of individuals who received only 9vHPV vaccine did not identify any new safety events related to 9vHPV administration and provides reassuring evidence of the favorable safety profile of the 9vHPV vaccine.