Vaccination With Moderate Coverage Eradicates Oncogenic Human Papillomaviruses If a Gender-Neutral Strategy Is Applied

Abstract

Background: Human papillomavirus (HPV) vaccination of girls with very high (>90%) coverage has the potential to eradicate oncogenic HPVs, but such high coverage is hard to achieve. However, the herd effect (HE) depends both on the HPV type and the vaccination strategy.

Methods: We randomized 33 Finnish communities into gender-neutral HPV16/18 vaccination, girls-only HPV16/18 vaccination, and hepatitis B virus vaccination arms. In 2007-2010, 11 662 of 20 513 of 40 852 of 39 420 resident boys/girls from 1992 to 1995 birth cohorts consented. In 2010-2014, cervicovaginal samples from vaccinated and unvaccinated girls at age 18.5 years were typed for HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68. Vaccine efficacy for vaccinated girls, HE for unvaccinated girls, and the protective effectiveness (PE) for all girls were estimated. We extended the community-randomized trial results about vaccination strategy with mathematical modeling to assess HPV eradication.

Results: The HE and PE estimates in the 1995 birth cohort for HPV18/31/33 were significant in the gender-neutral arm and 150% and 40% stronger than in the girls-only arm. Concordantly, HPV18/31/33 eradication was already predicted in adolescents/young adults in 20 years with 75% coverage of gender-neutral vaccination. With the 75% coverage, eventual HPV16 eradication was also predicted, but only with the gender-neutral strategy.

Conclusions: Gender-neutral vaccination is superior for eradication of oncogenic HPVs.

Trial registration: ClinicalTrials.gov NCT00534638.

Keywords: elimination; eradication; gender-neutral vaccination; herd effects; human papillomavirus.

Figure 1.

Herd effects (HEs) induced by human papillomavirus (HPV) vaccination. The first order HE from vaccinated girls to unvaccinated boys (girls-only vaccination), and from both vaccinated girls and boys to unvaccinated boys and girls (gender-neutral vaccination), as well as the second order HE effects from unvaccinated but herd-protected individuals are visualized (top panel). Herd effects take place towards younger HPV-vaccinated birth cohorts by increasing the number of vaccinated birth cohorts from HPV-infected ones (bottom panel). Herd effects between differentially protected parts of population are visualized (right panel).

Figure 2.

Prevalence reduction of human papillomavirus (HPV) types 18/31/33 in unvaccinated 18-year-old females by birth cohorts (1992–1995) and vaccination strategy: (Arm A) gender-neutral (49% girls and 23% boys HPV vaccinated [P for trend .0005]); (Arm B) girls-only (47% girls vaccinated [P for trend .092]); (Arm C) control, hepatitis B virus vaccination (P for trend .447) at the age of 12–15 years in 2007–2010. The trend of reduction by birth cohorts in the gender-neutral Arm A was stronger than that of the girls-only Arm B (P = .0556) or control Arm C (P = .0015).

Figure 3.

Modeled eradication of human papillomavirus (HPV) types 16 [■], 18 [■], and oncogenic HPV types with moderate (31 of 33) [■] or fast (35) [■] clearance rates by vaccine efficacy ([VE] 95%/80%/50%), with 75% girls-only vaccination coverage, with 50% boys and 75% girls vaccination coverage, and with 75% gender-neutral vaccination coverage.

Figure 4.

Modeled eradication of human papillomavirus (HPV) types 16 [■], 18 [■], and oncogenic HPV types with moderate (31 of 33) [■] or fast (35) [■] clearance rates by vaccine efficacy ([VE] 95%/80%/50%), with 50% girls-only vaccination coverage, with 25% boys and 50% girls vaccination coverage, and with 50% gender-neutral vaccination coverage.