Systematic review and meta-analysis of the association between naturally induced IgG, IgM and neutralising antibodies to HPV16 and newly detected cervical HPV16 infection outcomes.

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 (I 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.