Studies have been mixed on whether naturally acquired 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 (i.e. natural immunity).Studies have been mixed on whether naturally acquired 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 (i.e. natural immunity).
We searched the Medline and Embase databases for studies examining natural HPV immunity against subsequent genital type-specific HPV infection in females and males. We utilized random-effects models to derive pooled relative risk estimates for each HPV type.
We identified 14 eligible studies that included over 24,000 individuals from 18 countries that examined HPV natural immunity. We observed significant protection against subsequent infection with HPV16 (pooled RR=0.65, 95%CI=0.50-0.80) and HPV18 (pooled RR=0.70, 95%CI=0.43-0.98) in females but not in males (HPV16: pooled RR=1.22, 95%CI=0.67-1.77, p-heterogeneity=0.05; HPV18: pooled RR=1.50, 95%CI=0.46-2.55; p-heterogeneity=0.15). We also observed type-specific protection against subsequent infection for a combined measure of HPV6/11/31/33/35/45/52/58 in females (pooled RR=0.75, 95%CI=0.57-0.92). Natural immunity was also evident in females when restricting to studies that employed neutralizing assays, to those that used HPV persistence as an outcome, and to those that reported adjusted analyses (each p-value<0.05).
HPV antibodies acquired through natural infection provide modest protection against subsequent cervical HPV infection in females.