Peri-conceptional or pregnancy exposure of HPV vaccination and the risk of spontaneous abortion: a systematic review and meta-analysis

Background To assess whether the peri-conceptional or pregnancy exposure of human papillomavirus (HPV) vaccination would increase the risk of spontaneous abortion. Methods We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for clinical trials and observational studies that investigated the association between exposure of HPV vaccines (2vHPV, 4vHPV or 9vHPV) during peri-conceptional period or pregnancy and spontaneous abortion before 28 gestational weeks. We pooled data from 2vHPV, 4vHPV and 9vHPV separately. Subgroup analyses were conducted according to data sources, and raw data or adjusted data. Results Seven observational studies were eligible and all studies were low risk of bias. Meta-analyses suggested that 2vHPV vaccination did not increase the risk of spontaneous abortion regardless of exposure period during 90 days before last menstrual period (LMP) or pregnancy: risk ratio, 95% confidence intervals (RR, 95% CI), 1.15 (0.95-1.39), and 45 days before LMP or pregnancy: 1.28 (0.96-1.70). However, 2vHPV vaccination during Pre-45 days to LMP seemed to increase the risk of spontaneous abortion: 1.59 (1.04-2.45). The current evidence did not support the association between 4vHPV vaccination and spontaneous abortion regardless of exposure period during 45 days before LMP or pregnancy: 0.88 (0.73-1.06); and 45 days before LMP: 1.00 (0.80-1.24). Additionally, 9vHPV during within 30 days of conception also seemed to increase the risk: 2.04 (1.28-3.24). Conclusions The association between peri-conceptional or pregnancy exposure of HPV vaccine and spontaneous abortion is still uncertain, and additional research is warranted to assess the impact of exposure of HPV vaccination on spontaneous abortion.