Sex: F
Vaccine: HPV4
Symptoms: Abortion missed, Exposure during pregnancy
Clinical narrative: Information has been received from a physician via a literature article, concerning a pregnant female who on an unknown date was vaccinated with a dose of GARDASIL. On an unknown date the patient had a missed abortion. This report was part of a post-marketing surveillance program. Upon review of the file, retrospective was added in the obstetrical history. The primary investigator felt that missed abortion was not related to the study therapy. Upon internal review missed abortion was considered to be an other important medical event. Follow-up information has been received from another published article on 02-MAR-2015. Five years after vaccination, in subjects from the month 60 according-to-protocol cohort (seronegative and DNA negative for HPV type analyzed at baseline), serum neutralizing antibody (nAb) responses induced by HPV-16/18 vaccine remained 7.8-fold (18-26-y stratum), 5.6-fold (27-35-y stratum) and 2.3-fold (36-45-y stratum) higher than those induced by HPV-6/11/16/18 vaccine for HPV-16. For HPV-18, the fold differences were 12.1, 13.0 and 7.8, respectively. At month 60, all (100%) subjects in HPV-16/18 vaccine group and the majority (95.7%-97.5%) in HPV-6/11/16/18 vaccine group were seropositive for HPV-16. For HPV-18, the majority (98.1%-100%) of subjects in HPV-16/18 vaccine group were seropositive; however, seropositivity rates in HPV-6/11/16/18 vaccine group decreased considerably (61.1%-76.9%) across the 3 age strata. In the total vaccinated cohort (received = 1 dose regardless of baseline HPV serostatus and DNA status), geometric mean titers for anti-HPV-16 and anti-HPV-18 nAb were higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. Based on the 5-y data, piece-wise and modified power-law models predicted a longer durability of nAb response for HPV-16/18 vaccine compared to HPV-6/11/16/18 vaccine. Beyond the differences apparent between the vaccines in terms of immunogenicity and modeled persistence of antibody responses, comparative studies including clinical endpoints would be needed to determine whether differences exist in duration of vaccine induced protection. The aims of the current study was 1) to evaluate the serum antibody response of the HPV-16/18 and the HPV-6/11/16/18 vaccines measured by pseudovirion-based neutralization assay (PBNA) and enzyme-linked immunosorbent assay (ELISA) through month 60 (i.e., 54 months after completion of the full vaccination series); 2) to predict the long-term persistence of vaccine-induced anti-HPV-16 and anti-HPV-18 antibody responses (PBNA, ELISA) in subjects receiving a full series of vaccination by applying statistical models to antibody levels measured during the 5 year study duration; and 3) to evaluate safety up to month 60. A total of 1,106 women were enrolled and vaccinated with at least one dose of HPV-16/18 vaccine (N = 553) or HPV-6/11/16/18 vaccine (N = 553); all of whom were included in the total vaccinated cohort (TVC). Among them, 421 women consented to participate in the extended month 60 visit (213 in the HPV-16/18 vaccine group and 208 in the HPV-6/11/16/18 vaccine group); these subjects comprised the month 60 TVC. From month 0 to month 60, the proportion of subjects reporting events in the HPV-16/18 and HPV-6/11/16/18 vaccine groups (TVC) were comparable: serious adverse events (SAEs), 8% (n=44) in HPV-16/18 vaccine group and 6.7% (n=37) in HPV-6/11/16/18 vaccine group; medically significant conditions (MSCs), 46.8% (n=259) in HPV-16/18 vaccine group and 40.9% (n=226) in HPV-6/11/16/18 vaccine group; new onset chronic diseases (NOCDs), 7.1% (n=39) in HPV-16/18 vaccine group and 7.8% (n=43) in HPV-6/11/16/18 vaccine group; and new onset autoimmune disease (NOADs), 1.3% (n=7) in HPV-16/18 vaccine group and 2.4% (n=13) in HPV-6/11/16/18 vaccine group. A total of 172 pregnancies were reported up to month 60, with similar outcomes between vaccine groups. There were 71.9% (n=69) and 73.7% (n=56) live infants, respectively, in the HPV-16/18 and HPV-6/11/16/18 vaccine groups, with no unanticipated anomalies or outcomes. Fifteen (15.6%) and 11 cases (14.5%) of spontaneous abortion with no apparent congenital anomaly were reported in the HPV-16/18 and HPV-6/11/16/18 vaccine groups, respectively. Six (6.3%) and 3 cases (3.9%) of elective termination with no apparent congenital anomaly were reported in the HPV-16/18 and HPV-6/11/16/18 vaccine groups, respectively. This is one of several reports from the same literature with MARRS# (0911USA01430, 0911USA01519, 0911USA01520, 0911USA01521, 0911USA01522, 0911USA01523, 0911USA01525, 0911USA01526). Additional information has been requested. Reporter, literature information and the narrative have been updated.