Efficacy and immunogenicity of a single dose of human papillomavirus vaccine compared to no vaccination or standard three and two-dose vaccination regimens: A systematic review of evidence from clinical trials
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OBJECTIVES: This study aimed to systematically review the literature on the efficacy and immunogenicity of single-dose HPV vaccination compared to no vaccination or multi-dose schedules among vaccine trial participants. METHODS: Medline, EMBASE, Global Health Database and Cochrane Central Register of Controlled Trials were searched for publications and conference abstracts (dated January 1999-August 2018) using MeSH and non-MeSH terms for human papillomavirus AND vaccines AND (immunogenicity OR efficacy/effectiveness) AND dosage. Search results were screened against pre-specified eligibility criteria. Data were extracted from included articles, and a narrative synthesis conducted on efficacy against HPV16/18 infection and humoral immunogenicity. RESULTS: Seven of 6,523 unique records identified were included in the review. Six were nested observational studies of participants randomised to receive two or three doses in three large HPV vaccine trials, in which some participants did not complete their allocated schedules. One small pilot study prospectively allocated participants to receive one or no vaccine dose. Frequency of HPV16/18 infection was low (e.g. <1% for 12-month-persistent infection) in all vaccinated participants up to seven years post vaccination and did not significantly differ by number of doses (p > 0.05 in all cases). Frequency of infection was significantly lower in one-dose recipients compared to unvaccinated controls (p < 0.01 for all infection endpoints in each study). HPV16/18 seropositivity rates were high in all HPV vaccine recipients (100% in three of four studies reporting this endpoint), though antibody levels were lower with one compared to two or three doses. CONCLUSIONS: This review supports the premise that one HPV vaccine dose may be as effective in preventing HPV infection as multi-dose schedules in healthy young women. However, it also highlights the paucity of available evidence from purpose-designed, prospectively-randomised trials. Results from ongoing clinical trials assessing the efficacy and immunogenicity of single-dose HPV vaccination compared to currently-recommended schedules are awaited.
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Single-dose HPV vaccination provides comparable or non-inferior efficacy against persistent HPV infection compared with multi-dose schedules, with lower but sustained antibody levels for at least 11 years after vaccination.
“Notably, the IARC India trial with a quadrivalent vaccine, and the Costa Rica Trial with a bivalent vaccine, have shown comparable efficacy between single-dose and multi-dose schedules, with sustained antibody levels for at least 11 years after vaccination.”
From Evidence-based impact projections of single-dose human papillomavirus vaccination in India: a modelling study (2022) · cites this paper as [10]
The Discussion reports no difference in HPV16/18 infection incidence or persistence between one-, two-, and three-dose recipients through year four or seven, and says single-dose antibody levels were lower but remained relatively stable during follow-up. The Conclusions limit the reported follow-up to seven years; our copy does not support sustained antibody levels for at least 11 years. Page numbers were not available in the indexed passages. (LLM, conf=0.91)
Experimental — accuracy not yet measuredThe IARC India HPV vaccine trial currently provides the best data on single-dose protection because of its long follow-up and near-random assignment of participants to different dose schedules.
“which currently provides the best data on single-dose protection because of its long follow-up and near-random assignment of participants to different dose schedules.10, 11”
From Evidence-based impact projections of single-dose human papillomavirus vaccination in India: a modelling study (2022) · cites this paper as [10]
Section 3.2.1 reports HPV infection follow-up for the IARC India trial up to seven years. It says participants were originally randomized to two- or three-dose schedules, but the one-dose group arose after the trial was suspended, making the dose comparison observational—not a near-random assignment across all schedules. The review does not identify this trial as providing the best data. (LLM, conf=0.88)
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Key ethical considerations to guide the adjudication of a single-dose HPV vaccine schedule
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- Authors
- Whitworth, H. S., Gallagher, K. E., Howard, N., Mounier-Jack, S., Mbwanji, G., Kreimer, A. R., Basu, P., Kelly, H., Drolet, M., Brisson, M., & Watson-Jones, D.
- Affiliations
- London School of Hygiene & Tropical Medicine (GB)
- Mwanza Intervention Trials Unit (TZ)
- National Institutes of Health (US)
- Centre international de recherche sur le cancer (FR)
- Centre de recherche du CHU de Québec-Université Laval (CA)
- Université Laval (CA)
- Corresponding author
- Whitworth, Hilary S.
- ORCID
- Venue
- Vaccine
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 38
- Issue
- 6
- Pages
- 1302-1314
- ISSN
- 0264-410X (ISSN-L)
- OpenAlex
- W2995954663
- Cited by
- 118
- References
- 34
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 25 · 2023: 20 · 2022: 19 · 2021: 17 · 2020: 8
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Vaccine (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- National University of Singapore (submittedVersion)
- Funders
- PATH
- Topics
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Health Sciences › Medicine › Surgery › Genital Health and Disease
- Social Sciences › Health › Vaccine Coverage and Hesitancy
- Keywords
- HPV vaccine, single-dose vaccination, HPV16/18 infection, immunogenicity, vaccine efficacy, dosing regimen, seropositivity, antibody levels, HPV prevention, young women
- MeSH terms
- Immunogenicity, Vaccine, Female, Humans, Immunization Schedule, Vaccination, Randomized Controlled Trials as Topic, Papillomavirus Infections, Human papillomavirus 18, Human papillomavirus 16, Papillomavirus Vaccines, Immunity, Humoral, Observational Studies as Topic
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