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Abstract
Background It is unclear whether recurrent cervical human papillomavirus type 16 (HPV16) infections can be prevented by naturally induced HPV16 antibodies in unvaccinated healthy women.
Methods We systematically searched the literature for studies that prospectively evaluated the association between HPV16 naturally induced IgG, IgM, and neutralising antibodies and newly detected cervical HPV16 infection in unvaccinated women. Data were quantitatively summarised by random effect meta-analysis.
Results Naturally induced HPV16 IgG and neutralising antibodies were negatively associated with newly detected HPV16 infection (relative risk (RR) (95% confidence interval (CI))=0.71 (0.63 to 0.80) and 0.54 (0.36 to 0.73), respectively). HPV16 antibodies tend to offer protection against subsequent HPV16 DNA detection in young women (RR (95% CI)=0.65 (0.55 to 0.74)), but not in women aged over 25 years (RR (95% CI)=0.88 (0.73 to 1.04)). HPV16 IgG antibodies were also negatively associated with persistent HPV16 infection (adjusted RR=0.67 (0.56 to 0.78)). There was high heterogeneity between studies (I2 statistic=63.9%; p=0.007), and most had low risk of bias. We did not find studies evaluating IgM antibodies.
Conclusion Seroreactivity to HPV16 infection seems to provide moderate protection against newly detected cervical HPV16 infection outcomes in unvaccinated women. However, protection seems to be affected by age. These findings should be considered when evaluating public health interventions against HPV.
PROSPERO registration number CRD42022339579.
- META-ANALYSIS
- Human Papillomavirus
- SEROLOGY
- SYSTEMATIC REVIEW
- INFECTION CONTROL
Data availability statement
All relevant data are included in the article or uploaded as online supplemental material. The data that support the findings of this study and Stata codes are available on request from the corresponding author.
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Data availability statement
All relevant data are included in the article or uploaded as online supplemental material. The data that support the findings of this study and Stata codes are available on request from the corresponding author.
Footnotes
Handling editor David Regan
Contributors AT, HT, and ELF conceptualised the study. AT and AP developed the search strategy. AP performed the literature search. AT and PSAS independently did the screening and data extraction, supported by HT. AT, JN, and HT planned the statistical analysis. AT performed all analyses. AT, PSAS, JN, ELF, and HT interpreted the results. AT wrote the manuscript. All authors revised and approved the final version of the manuscript. AT is the guarantor.
Funding CHU Sainte-Justine Foundation and Université de Montréal: scholarships awarded to AT.
Competing interests AT reports scholarships received from the CHU Sainte-Justine Foundation and Université de Montréal during the conduct of this study. PSAS received fellowship provided by Conselho Nacional de Desenvolvimento Científico e Tecnologico (CNPq)/Brazil (protocol number 311540/2022-8). JN discloses occasional lecture fees from Merck. ELF discloses occasional advisory work for Merck, GSK, Roche, BD. Honoraria from Elsevier, Oxford University Press, and Elifesciences. HT reports receiving occasional lecture fees from Merck and unrestricted grants from ViiV Healthcare. The other authors report no potential conflicts of interest.
Provenance and peer review Not commissioned; externally peer-reviewed.
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