Impact of gender‐neutral or girls‐only vaccination against human papillomavirus—Results of a community‐randomized clinical trial (I)

Abstract

Human papillomavirus (HPV) vaccine is efficacious but the real-life effectiveness of gender-neutral and girls-only vaccination strategies is unknown. We report a community-randomized trial on the protective effectiveness [(PE) = vaccine efficacy (VE) + herd effect (HE)] of the two strategies among females in virtually HPV vaccination naïve population. We randomized 33 Finnish communities into Arm A) gender-neutral vaccination with AS04-adjuvanted HPV16/18 vaccine (11 communities), Arm B) HPV vaccination of girls and hepatitis B-virus (HBV) vaccination of boys (11 communities) or Arm C) gender-neutral HBV vaccination (11 communities). All resident 39,420 females and 40,852 males born 1992-95 were invited in 2007-09. Virtually all (99%) 12- to 15-year-old participating males (11,662) and females (20,513) received three doses resulting in uniform 20-30% male and 50% female vaccination coverage by birth cohort. Four years later (2010-14) 11,396 cervicovaginal samples obtained from 18.5 year-old women were tested for HPV DNA, and prevalence of cervical HPV infections by trial arm and birth cohort was the main outcome measure. VEs against HPV16/18 varied between 89.2% and 95.2% across birth cohorts in arms A and B. The VEs against non-vaccine types consistent with cross-protection were highest in those born 1994-95 for HPV45 (VE 82.8%; VE 86.1%) and for HPV31 (VE 77.6%, VE 84.6%). The HEs in the non HPV-vaccinated were statistically significant in those born 1994-95 for HPV18 (HE 51.0%; 95% CI 8.3-73.8, HE 47.2%; 6.5-70.2) and for HPV31/33 in arm A (HE 53.7%; 22.1-72.5). For HPV16 and 45 no significant herd effects were detected. PE estimates against HPV16/18 were similar by both strategies (PE 58.1%; 45.1-69.4; PE 55.7%; 42.9-66.6). PE estimates against HPV31/33 were higher by the gender-neutral vaccination (PE 60.5%; 43.6-73.4; PE 44.5%; 24.9-60.6). In conclusion, while gender-neutral strategy enhanced the effectiveness of HPV vaccination for cross-protected HPV types with low to moderate coverage, high coverage in males appears to be key to providing a substantial public health benefit also to unvaccinated females. Trial registration www.clinicaltrials.gov.com NCT000534638.

Assessment of herd effects among women and heterosexual men after girls‐only HPV16/18 vaccination in the Netherlands: A repeated cross‐sectional study

“…Among heterosexual men, the decline in HPV prevalence was larger for HPV18 than for HPV16, which is in line with data from Finland where also larger herd effects were observed for HPV18 . Higher herd effects for HPV18 could be explained by a lower basic reproduction number (as a consequence of a higher clearance relative to HPV16) .…”

“…Surveillance studies have shown a decrease in the HPV16/18 prevalence since the introduction of vaccination . Some studies have also shown decreases in the HPV16/18 prevalence among unvaccinated women . This decrease among unvaccinated women is attributed to herd protection in men, yet there is limited information about trends in HPV prevalence among men, especially after bivalent HPV vaccination.…”

Occurrence of human papillomavirus (HPV) type replacement by sexual risk‐taking behaviour group: Post‐hoc analysis of a community randomized clinical trial up to 9 years after vaccination (IV)

“…5,6 However, among the non-HPV vaccinated women the protective impact of herd effect was not observed for HPV16 or HPV31/33/35 among the core-group. 5,6 However, among the non-HPV vaccinated women the protective impact of herd effect was not observed for HPV16 or HPV31/33/35 among the core-group.…”

“…The HPV51 and Table 1. 5 Questionnaire data obtained at the age of 22 years from vaccinated participants only. 2 HPV 16/18 cross-vaccinated after cervical sampling at the first follow-up visit.…”

Novel approaches for the design, delivery and administration of vaccine technologies

“…Therefore, intravaginal vaccination has been explored as an option to prevent sexually transmitted infections [180]. One reason this method of vaccination has not been explored as extensively as others could be that it only has the ability to immunize females in a population in which, increasingly, it is being shown that it does not provide sufficient herd immunity, especially when considering the impact of immunocompromised females who are unable to receive the vaccinations [182,183]. One reason this method of vaccination has not been explored as extensively as others could be that it only has the ability to immunize females in a population in which, increasingly, it is being shown that it does not provide sufficient herd immunity, especially when considering the impact of immunocompromised females who are unable to receive the vaccinations [182,183].…”