Natural Acquired Immunity Against Subsequent Genital Human Papillomavirus Infection: A Systematic Review and Meta-analysis

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Background. Studies have been mixed on whether naturally acquired human papillomavirus (HPV) antibodies may protect against subsequent HPV infection. We performed a systematic review and meta-analysis to assess whether naturally acquired HPV antibodies protect against subsequent genital HPV infection (ie, natural immunity).

Methods. We searched the MEDLINE and EMBASE databases for studies examining natural HPV immunity against subsequent genital type-specific HPV infection in female and male subjects. We used random-effects models to derive pooled relative risk (RR) estimates for each HPV type.

Results. We identified 14 eligible studies that included >24 000 individuals from 18 countries that examined HPV natural immunity. We observed significant protection against subsequent infection in female subjects with HPV-16 (pooled RR, 0.65; 95% confidence interval, .50–.80) and HPV-18 (0.70; .43–.98) but not in male subjects (HPV-16: 1.22; .67–1.77 [P = .05 (test for heterogeneity)]; HPV-18: 1.50; .46–2.55; [P = .15]). We also observed type-specific protection against subsequent infection for a combined measure of HPV-6/11/31/33/35/45/52/58 in female subjects (pooled RR, 0.75; 95% confidence interval, .57–.92). Natural immunity was also evident in female subjects when analyses were restricted to studies that used neutralizing assays, used HPV persistence as an outcome, or reported adjusted analyses (each P < .05).

Conclusions. HPV antibodies acquired through natural infection provide modest protection against subsequent cervical HPV infection in female subjects.

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