Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Aug 3:52:101585.
doi: 10.1016/j.eclinm.2022.101585. eCollection 2022 Oct.

Immunogenicity, safety, and efficacy of the HPV vaccines among people living with HIV: A systematic review and meta-analysis

Lisa Staadegaard  1 , Minttu M Rönn  2 , Nirali Soni  1   3 , Meghan E Bellerose  2 , Paul Bloem  4 , Marc Brisson  5   6 , Mathieu Maheu-Giroux  7 , Ruanne V Barnabas  8 , Melanie Drolet  6 , Philippe Mayaud  9 , Shona Dalal  4 , Marie-Claude Boily  1   3
Affiliations

Immunogenicity, safety, and efficacy of the HPV vaccines among people living with HIV: A systematic review and meta-analysis

Lisa Staadegaard et al. EClinicalMedicine. .

Abstract

Background: Vaccines have been demonstrated to protect against high-risk human papillomavirus infection (HPV), including HPV-16/18, and cervical lesions among HIV negative women. However, their efficacy remains uncertain for people living with HIV (PLHIV).We systematically reviewed available evidence on HPV vaccine on immunological, virological, or other biological outcomes in PLHIV.

Methods: We searched five electronic databases (PubMed, Medline and Embase, clinicaltrials.gov and the WHO clinical trial database) for longitudinal prospective studies reporting immunogenicity, virological, cytological, histological, clinical or safety endpoints following prophylactic HPV vaccination among PLHIV. We included studies published by February 11th, 2021. We summarized results, assessed study quality, and conducted meta-analysis and subgroup analyses, where possible.

Findings: We identified 43 publications stemming from 18 independent studies (Ns =18), evaluating the quadrivalent (Ns =15), bivalent (Ns =4) and nonavalent (Ns =1) vaccines. A high proportion seroconverted for the HPV vaccine types. Pooled proportion seropositive by 28 weeks following 3 doses with the bivalent, quadrivalent, and nonavalent vaccines were 0.99 (95% confidence interval: 0.95-1.00, Ns =1), 0.99 (0.98-1.00, Ns =9), and 1.00 (0.99-1.00, Ns =1) for HPV-16 and 0.99 (0.96-1.00, Ns =1), 0.94 (0.91-0.96, Ns =9), and 1.00 (0.99-1.00, Ns =1) for HPV-18, respectively. Seropositivity remained high among people who received 3 doses despite some declines in antibody titers and lower seropositivity over time, especially for HPV-18, for the quadrivalent than the bivalent vaccine, and for HIV positive than negative individuals. Seropositivity for HPV-18 at 29-99 weeks among PLHIV was 0.72 (0.66-0.79, Ns =8) and 0.96 (0.92-0.99, Ns =2) after 3 doses of the quadrivalent and bivalent vaccine, respectively and 0.94 (0.90-0.98, Ns =3) among HIV-negative historical controls. Evidence suggests that the seropositivity after vaccination declines over time but it can lasts at least 2-4 years. The vaccines were deemed safe among PLHIV with few serious adverse events. Evidence of HPV vaccine efficacy against acquisition of HPV infection and/or associated disease from the eight trials available was inconclusive due to the low quality.

Interpretation: PLHIV have a robust and safe immune response to HPV vaccination. Antibody titers and seropositivity rates decline over time but remain high. The lack of a formal correlate of protection and efficacy results preclude definitive conclusions on the clinical benefits. Nevertheless, given the burden of HPV disease in PLHIV, although the protection may be shorter or less robust against HPV-18, the robust immune response suggests that PLHIV may benefit from receiving HPV vaccination after acquiring HIV. Better quality studies are needed to demonstrate the clinical efficacy among PLHIV.

Funding: World Health Organization. MRC Centre for Global Infectious Disease Analysis, Canadian Institutes of Health Research, UK Medical Research Council (MRC).

Keywords: Cervical cancer; HIV; Human papilloma virus; Meta-analysis; Vaccination.

PubMed Disclaimer

Conflict of interest statement

LS has received funding from Sanofi Pasteur/AstraZeneca outside of the submitted work. MMR reports funding from Charles A King Trust Postdoctoral Fellowship and Harvard Data Science Institute, and travel support to attend meetings for cervical cancer elimination from the WHO and Canadian Institute of Health Research, all outside of the submitted work. RVB received abstract and manuscript writing support from Regeneron Pharmaceuticals, outside the submitted work. MMG reports an investigator-sponsored research grant from Gilead Sciences Inc., and contractual arrangements from the Institut national de santé publique du Québec (INSPQ), the Institut d'excellence en santé et services sociaux (INESSS), the World Health Organization, and the Joint United Nations Programme on HIV/AIDS (UNAIDS), all outside of the submitted work. MB reports funding from Bill & Melinda Gates Foundation (grant number OPP48979), outside the submitted work.

Figures

Figure 1
Figure 1
Search results and study selection. Abbreviations: Np = Number of publications, Ns= Number of Studies.
Figure 2
Figure 2
Seropositivity to A) HPV-16, B) HPV-18, C) HPV-6 and D) HPV-11 following vaccination with the bivalent (bHPV), quadrivalent (qHPV), or nonavalent (9vHPV) vaccines among PLHIV who were seronegative for the specific HPV type at baseline (Number of independent trials, Ns =13). Estimates are stratified by number of doses and timing of measurement since the first dose in the vaccination schedule. One asterisk(*) indicates which study estimates were included in pooled estimates (one per study - the longest follow up time). Two asterisks (**) indicates there was only single estimate for a given vaccine type, which was not pooled. Vaccine types are colour-coded: black = qHPV, teal = bHPV, and orange = 9vHPV. Abbreviations: Both (B), female (F) or male (M); N= Trial sample size; BR=Brazil, CAN=Canada, Den=Denmark, IND=India, KEN=Kenya, PR= Puerto Rico, SA=South Africa, USA=United States of America; Age ranges are in years; cLIA= chemiluminescence immunoassay, Neutr. assay = neutralization assay, IgG-LIA = line immunoassay, PBNA = pseudovirion-based neutralisation assay.
Figure 2
Figure 2
Seropositivity to A) HPV-16, B) HPV-18, C) HPV-6 and D) HPV-11 following vaccination with the bivalent (bHPV), quadrivalent (qHPV), or nonavalent (9vHPV) vaccines among PLHIV who were seronegative for the specific HPV type at baseline (Number of independent trials, Ns =13). Estimates are stratified by number of doses and timing of measurement since the first dose in the vaccination schedule. One asterisk(*) indicates which study estimates were included in pooled estimates (one per study - the longest follow up time). Two asterisks (**) indicates there was only single estimate for a given vaccine type, which was not pooled. Vaccine types are colour-coded: black = qHPV, teal = bHPV, and orange = 9vHPV. Abbreviations: Both (B), female (F) or male (M); N= Trial sample size; BR=Brazil, CAN=Canada, Den=Denmark, IND=India, KEN=Kenya, PR= Puerto Rico, SA=South Africa, USA=United States of America; Age ranges are in years; cLIA= chemiluminescence immunoassay, Neutr. assay = neutralization assay, IgG-LIA = line immunoassay, PBNA = pseudovirion-based neutralisation assay.
Figure 2
Figure 2
Seropositivity to A) HPV-16, B) HPV-18, C) HPV-6 and D) HPV-11 following vaccination with the bivalent (bHPV), quadrivalent (qHPV), or nonavalent (9vHPV) vaccines among PLHIV who were seronegative for the specific HPV type at baseline (Number of independent trials, Ns =13). Estimates are stratified by number of doses and timing of measurement since the first dose in the vaccination schedule. One asterisk(*) indicates which study estimates were included in pooled estimates (one per study - the longest follow up time). Two asterisks (**) indicates there was only single estimate for a given vaccine type, which was not pooled. Vaccine types are colour-coded: black = qHPV, teal = bHPV, and orange = 9vHPV. Abbreviations: Both (B), female (F) or male (M); N= Trial sample size; BR=Brazil, CAN=Canada, Den=Denmark, IND=India, KEN=Kenya, PR= Puerto Rico, SA=South Africa, USA=United States of America; Age ranges are in years; cLIA= chemiluminescence immunoassay, Neutr. assay = neutralization assay, IgG-LIA = line immunoassay, PBNA = pseudovirion-based neutralisation assay.
Figure 2
Figure 2
Seropositivity to A) HPV-16, B) HPV-18, C) HPV-6 and D) HPV-11 following vaccination with the bivalent (bHPV), quadrivalent (qHPV), or nonavalent (9vHPV) vaccines among PLHIV who were seronegative for the specific HPV type at baseline (Number of independent trials, Ns =13). Estimates are stratified by number of doses and timing of measurement since the first dose in the vaccination schedule. One asterisk(*) indicates which study estimates were included in pooled estimates (one per study - the longest follow up time). Two asterisks (**) indicates there was only single estimate for a given vaccine type, which was not pooled. Vaccine types are colour-coded: black = qHPV, teal = bHPV, and orange = 9vHPV. Abbreviations: Both (B), female (F) or male (M); N= Trial sample size; BR=Brazil, CAN=Canada, Den=Denmark, IND=India, KEN=Kenya, PR= Puerto Rico, SA=South Africa, USA=United States of America; Age ranges are in years; cLIA= chemiluminescence immunoassay, Neutr. assay = neutralization assay, IgG-LIA = line immunoassay, PBNA = pseudovirion-based neutralisation assay.
Figure 3
Figure 3
Average geometric mean antibody titre (GMT) for A) HPV-16, B) HPV-18, C) HPV-6, D) HPV-11 over time after administration of the quadrivalent vaccine in different PLHIV study populations (children: <18, adults: ≥18, and mix: both children & adults), stratified by baseline HPV status and type of test (Ns = 11 trials). On each panel, each line (or unique data point when only one time point was reported) is the mean from a different study. Ns on each panel indicate the number of studies included. Arrows indicate timing of vaccine doses. Dotted line indicates cut-off value for seropositivity for the cLIA assay. Mean (range) GMT levels (excluding neutralization assay results) at 28 weeks across studies are higher for HPV-16 (mean: 2239, range 504-5173 mMu/ml).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kojic EM, Rana AI, Cu-Uvin S. Human papillomavirus vaccination in HIV-infected women: Need for increased coverage. Expert Rev Vaccines. 2016;15(1):105–117. - PMC - PubMed
    1. Van de Velde N, Boily M-C, Drolet M, et al. Population-level impact of the bivalent, quadrivalent, and nonavalent human papillomavirus vaccines: a model–based analysis. JNCI J Natl Cancer Inst. 2012;104(22):1712–1723. - PubMed
    1. Cervical cancer. [cited 2022 Jan 19]. Available from: https://www.who.int/news-room/fact-sheets/detail/cervical-cancer
    1. RIVM. Projected direct benefit of vaccination against HPV. [cited 2022 Feb 19]. Available from: https://www.rivm.nl/documenten/hpv-vaccination-in-netherlands
    1. PATH. Expanding access to HPV vaccines. [cited 2022 Feb 19]. Available from: https://www.path.org/media-center/expanding-access-hpv-vaccines-path-eva...

LinkOut - more resources