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

J Infect Dis. 2016 May 1;213(9):1444-54. doi: 10.1093/infdis/jiv753. Epub 2015 Dec 21.


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.

Keywords: antibodies; cervix; human papillomavirus; natural immunity; serology.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Intramural
  • Review
  • Systematic Review

MeSH terms

  • Adaptive Immunity*
  • Adolescent
  • Adult
  • Antibodies, Viral / blood
  • Female
  • Human papillomavirus 16 / immunology*
  • Human papillomavirus 18 / immunology*
  • Humans
  • Male
  • Middle Aged
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / immunology*
  • Young Adult


  • Antibodies, Viral