Clinical trial and post-licensure safety profile of a prophylactic human papillomavirus (types 6, 11, 16, and 18) l1 virus-like particle vaccine.
BACKGROUND
We describe the safety of the human papillomavirus (HPV)-6/11/16/18 vaccine using updated clinical trial data (median follow-up time of 3.6 years) and summarize up to 3 years of post-licensure surveillance.


METHODS
In 5 clinical trials, 21,480 girls/women aged 9 to 26 years and boys aged 9 to 16 years received >or=1 dose of HPV-6/11/16/18 vaccine or placebo. All serious and non-serious adverse experiences (AEs) and new medical conditions were recorded for the entire study period(s). As of June 2009, >25 million doses of HPV-6/11/16/18 vaccine had been distributed in the United States with >50 million doses globally. Post-licensure safety as summarized by the Centers for Disease Control and Prevention using the United States Vaccine Adverse Event Reporting System database is also reported.


RESULTS
Eight subjects experienced a treatment-related serious AE (0.05% vaccine; 0.02% placebo). Of 18 deaths (0.1% vaccine; 0.1% placebo), all were considered unrelated to study treatment. New medical conditions which were potentially consistent with autoimmune phenomena were reported in 2.4% of both vaccine and placebo recipients. Pain, the most common injection-site AE, occurred more frequently with vaccine (81% vaccine; 75% placeboaluminum; 45% placebo-saline). No differences were seen in the incidence of the most common non-serious AEs-headache and pyrexia. The Vaccine Adverse Event Reporting System has received 14,072 reports for the HPV-6/11/16/18 vaccine since licensure, with only 7% being serious AEs, about half the average reported for licensed vaccines in general.


CONCLUSIONS
HPV-6/11/16/18 vaccination was associated with more injection-site pain than placebo but similar incidences of systemic and serious AEs and new medical conditions potentially consistent with autoimmune phenomena. Based on review of post-licensure safety information, the benefits of vaccination to prevent the majority of genital tract precancers and cancers continue to far outweigh its risks.
Block
Stan L
SL
Kentucky Pediatric/Adult Research, Inc., Bardstown, KY 40004, USA. sblock@pol.net
Brown
Darron R
DR
Chatterjee
Archana
A
Gold
Michael A
MA
Sings
Heather L
HL
Meibohm
Anne
A
Dana
Adrian
A
Haupt
Richard M
RM
Barr
Eliav
E
Tamms
Gretchen M
GM
Zhou
Haiping
H
Reisinger
Keith S
KS
D000293:Adolescent; D000328:Adult; D002648:Child; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005334:Fever; D006261:Headache; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D006801:Humans; D015994:Incidence; D008297:Male; D010146:Pain; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000009:adverse effects* / Q000276:immunology*; D010919:Placebos / Q000008:administration & dosage; D011358:Product Surveillance, Postmarketing; D014481:United States; D022721:Vaccines, Virosome / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D053918:Papillomavirus Vaccines; D010919:Placebos; D022721:Vaccines, Virosome