Background: Immunological differences between males and females in response to viral vaccines are well known. This the first review to examine them for the Human Papilloma Virus.
Methods: We conducted a systematic review and meta-analysis of the immunogenicity of the Quadrivalent Human Papilloma Virus Vaccine qHPVV. We searched Medline, Embase, and CENTRAL for trials published until September 17, 2019. Inclusion criteria were 3-doses and reporting geometric mean titers (GMTs). We performed random-effects meta-analyses and meta-regression separated by age group and sex.
Results: Our search yielded 1809 unique studies. 334 full texts were screened and data from 18 studies were extracted. Females had higher pooled geometric mean titers than males in all age groups. Log transformed GMTs in male children (<16) years were: against HPV6: 6·62 (95% CI 6·29-6·94; I2 = 86·0%), against HPV11: 7·07 (95% CI 6·90-7·23; I2 = 63.1%), against HPV16: 8·53 (95% CI 8·28-8·78; I2 = 73·0%), and against HPV18 7·21 (95% CI 7·08-7·34; I2 = 26·4%). In females: against HPV6 7·10 (95% CI 6·79-7·41; I2 = 96·6%), HPV11: 7·32 (95% CI 7·15-7·50; I2 = 90·6%), HPV16: 8·71 (95% CI 8·52-8·91; I2 = 90·2%), and HPV18 7·35 (95% CI 7·11-7·58; I2 = 92·7%). In the meta-regression, the sexual difference was significant for HPV6 (p = 0·022) with a similar tendency for HPV11 (p = 0·066) and HPV18 (p = 0·079). Immunogenicity was significantly higher in children (<16) than in adults (p < 0·001).
Conclusion: Females have higher antibody titers against HPV after receiving the qHPVV than do males. The difference is bigger in low-risk HPV strains. Adjusting the doses and schedules for each sex should be explored further.
Keywords: Antibody response; Cervical cancer; Human Papilloma Virus; Immunogenicity; Quadrivalent HPV vaccine; Sex difference.