Evidence from Outcomes : Gender-Neutral 2vHPV Vaccination at Moderate Coverage Drives Rapid Depletion of HPV16/18 Among Vaccinated and Unvaccinated Women
(2026) In Viruses 18(1).- Abstract
Human papillomavirus (HPV) vaccination may eventually eradicate oncogenic vaccine-targeted HPVs but only with a strategy that also protects unvaccinated individuals. We compared the impact of gender-neutral and girls-only vaccination strategies on the indirect and direct protection of unvaccinated and vaccinated young women against HPV16/18 infection using HPV16/18 seropositivity and PCR positivity 3–7 years post vaccination as the outcome measure. A total of 33 Finnish communities were randomized to one of three vaccination strategies: bivalent gender-neutral HPV vaccination (Arm A), girls-only HPV vaccination (Arm B), or control hepatitis B vaccination (Arm C). All individuals born between 1992 and 1995 and residing in these... (More)
Human papillomavirus (HPV) vaccination may eventually eradicate oncogenic vaccine-targeted HPVs but only with a strategy that also protects unvaccinated individuals. We compared the impact of gender-neutral and girls-only vaccination strategies on the indirect and direct protection of unvaccinated and vaccinated young women against HPV16/18 infection using HPV16/18 seropositivity and PCR positivity 3–7 years post vaccination as the outcome measure. A total of 33 Finnish communities were randomized to one of three vaccination strategies: bivalent gender-neutral HPV vaccination (Arm A), girls-only HPV vaccination (Arm B), or control hepatitis B vaccination (Arm C). All individuals born between 1992 and 1995 and residing in these communities (n = 80,272) were invited to participate. Overall, 11,662 males and 20,513 females consented, corresponding to vaccination coverages of 25% and 45%, respectively, in 2007–2009. Between 2010 and 2014, 11,396 cervical samples were collected from 18-year-old participants and subjected to high-throughput PCR-based HPV genotyping. In addition, serum samples were obtained from 8022 unvaccinated women under 23 years of age residing in Arm A (n = 2657), Arm B (n = 2691), or Arm C (n = 2674) communities during the pre-vaccination (2005–2010) and post-vaccination (2011–2016) periods. To assess indirect vaccine effects using PCR and serological outcomes in unvaccinated women, we compared reductions in HPV16/18 prevalence from baseline within the gender-neutral and girls-only vaccination arms, using the control arm as a reference. A significant decrease in seroprevalence between the pre- and post-vaccination periods was detected in the gender-neutral communities for both HPV16 (seroprevalence ratio = 0.64) and HPV18 (0.72), whereas no comparable reductions were observed in the girls-only or control communities. In contrast, a significant reduction in HPV18 PCR-based prevalence from baseline to the post-vaccination period was observed in both the gender-neutral (0.32) and girls-only (0.61) communities. However, after accounting for ratios of seroprevalence rations for secular trends, the corresponding decrease in HPV18 seroprevalence was no longer statistically significant. Vaccine efficacy (VE) in Arm A or Arm B versus Arm C of vaccinated women measured the direct protection of vaccinated women by vaccination strategy. HPV16/18 VEs varied between 89% and 96% with some indication of herd effect against HPV18. Robust effectiveness of vaccination against PCR-confirmed cervical HPV16/18 infections, along with rapid indirect protection against HPV16/18 and HPV18 infections, was evident even with vaccination reaching only 25% and 45% coverage. Our results suggest that vaccine efficacy and herd effect induced by gender-neutral 2vHPV vaccination sets the stage for comprehensive HPV eradication, including the unvaccinated in the vaccinated communities.
(Less)
- author
- Lehtinen, Matti ; Pimenoff, Ville N. ; Eriksson, Tiina ; Lagheden, Camilla LU ; Söderlund-Strand, Anna LU ; Surcel, Heljä Marja and Dillner, Joakim LU
- organization
- publishing date
- 2026-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- community randomized, gender-neutral, HPV eradication, HPV genotyping, HPV vaccination, serology
- in
- Viruses
- volume
- 18
- issue
- 1
- article number
- 99
- publisher
- MDPI AG
- external identifiers
-
- scopus:105028488000
- pmid:41600862
- ISSN
- 1999-4915
- DOI
- 10.3390/v18010099
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2026 by the authors.
- id
- 46742b22-3637-4f49-b0d3-2972afd2795a
- date added to LUP
- 2026-02-23 16:54:44
- date last changed
- 2026-03-24 00:12:39
@article{46742b22-3637-4f49-b0d3-2972afd2795a,
abstract = {{<p>Human papillomavirus (HPV) vaccination may eventually eradicate oncogenic vaccine-targeted HPVs but only with a strategy that also protects unvaccinated individuals. We compared the impact of gender-neutral and girls-only vaccination strategies on the indirect and direct protection of unvaccinated and vaccinated young women against HPV16/18 infection using HPV16/18 seropositivity and PCR positivity 3–7 years post vaccination as the outcome measure. A total of 33 Finnish communities were randomized to one of three vaccination strategies: bivalent gender-neutral HPV vaccination (Arm A), girls-only HPV vaccination (Arm B), or control hepatitis B vaccination (Arm C). All individuals born between 1992 and 1995 and residing in these communities (n = 80,272) were invited to participate. Overall, 11,662 males and 20,513 females consented, corresponding to vaccination coverages of 25% and 45%, respectively, in 2007–2009. Between 2010 and 2014, 11,396 cervical samples were collected from 18-year-old participants and subjected to high-throughput PCR-based HPV genotyping. In addition, serum samples were obtained from 8022 unvaccinated women under 23 years of age residing in Arm A (n = 2657), Arm B (n = 2691), or Arm C (n = 2674) communities during the pre-vaccination (2005–2010) and post-vaccination (2011–2016) periods. To assess indirect vaccine effects using PCR and serological outcomes in unvaccinated women, we compared reductions in HPV16/18 prevalence from baseline within the gender-neutral and girls-only vaccination arms, using the control arm as a reference. A significant decrease in seroprevalence between the pre- and post-vaccination periods was detected in the gender-neutral communities for both HPV16 (seroprevalence ratio = 0.64) and HPV18 (0.72), whereas no comparable reductions were observed in the girls-only or control communities. In contrast, a significant reduction in HPV18 PCR-based prevalence from baseline to the post-vaccination period was observed in both the gender-neutral (0.32) and girls-only (0.61) communities. However, after accounting for ratios of seroprevalence rations for secular trends, the corresponding decrease in HPV18 seroprevalence was no longer statistically significant. Vaccine efficacy (VE) in Arm A or Arm B versus Arm C of vaccinated women measured the direct protection of vaccinated women by vaccination strategy. HPV16/18 VEs varied between 89% and 96% with some indication of herd effect against HPV18. Robust effectiveness of vaccination against PCR-confirmed cervical HPV16/18 infections, along with rapid indirect protection against HPV16/18 and HPV18 infections, was evident even with vaccination reaching only 25% and 45% coverage. Our results suggest that vaccine efficacy and herd effect induced by gender-neutral 2vHPV vaccination sets the stage for comprehensive HPV eradication, including the unvaccinated in the vaccinated communities.</p>}},
author = {{Lehtinen, Matti and Pimenoff, Ville N. and Eriksson, Tiina and Lagheden, Camilla and Söderlund-Strand, Anna and Surcel, Heljä Marja and Dillner, Joakim}},
issn = {{1999-4915}},
keywords = {{community randomized; gender-neutral; HPV eradication; HPV genotyping; HPV vaccination; serology}},
language = {{eng}},
number = {{1}},
publisher = {{MDPI AG}},
series = {{Viruses}},
title = {{Evidence from Outcomes : Gender-Neutral 2vHPV Vaccination at Moderate Coverage Drives Rapid Depletion of HPV16/18 Among Vaccinated and Unvaccinated Women}},
url = {{http://dx.doi.org/10.3390/v18010099}},
doi = {{10.3390/v18010099}},
volume = {{18}},
year = {{2026}},
}