Correlation between cervical HPV DNA detection and HPV16 seroreactivity measured with L1-only and L1+L2 viral capsid antigens

J Med Microbiol. 2020 Jul;69(7):960-970. doi: 10.1099/jmm.0.001213.


Introduction. Persistent human papillomavirus (HPV) type 16 infection is the main causal agent of cervical cancer. Most HPV infections clear spontaneously within 1-2 years. Although not all infected women develop detectable HPV antibodies, about 60-70 % seroconvert and retain their antibodies at low levels.Aim. We investigated if cervical HPV16 DNA positivity was associated with HPV16 seroreactivity measured with two different antigen formulations. We assessed if associations were influenced by co-infection with other HPV types and HPV16 viral load.Methodology. We used baseline data for women participating in the Ludwig-McGill cohort, a longitudinal investigation of the natural history of HPV infection and cervical neoplasia. The study enrolled 2462 Brazilian women from 1993 to 1997 (pre-vaccination). ELISA assays were based on L1-only or L1+L2 virus-like particles (VLPs). Seroreactivity was expressed as normalized absorbance ratios. HPV genotyping and viral load were evaluated by PCR protocols. Pearson's r was used to measure correlations between interval-scaled variables. Serological accuracy in HPV16 DNA detection was assessed using receiver operating characteristic (ROC) curves. We analysed the association between HPV DNA positivity and HPV16 seroreactivity by linear regression.Results. Correlations between L1+L2 and L1-only VLPs for detection of HPV16 were poor (r=0.43 and 0.44 for dilutions 1 : 10 and 1 : 50, respectively). The protocol with the best accuracy was L1+L2 VLPs at serum dilution 1 : 10 (ROC area=0.73, 95 % CI: 0.65-0.85). HPV16 DNA positivity was correlated with HPV16 seroreactivity and was not influenced by co-infection or viral load. To a lesser degree, HPV16 seroreactivity was correlated with infection by other Alpha-9 papillomavirus species.Conclusion. HPV16 DNA positivity and HPV16 seroreactivity are strongly correlated. L1+L2 VLPs perform better than L1-only VLPs for detecting IgG antibodies to HPV16 in women infected with HPV16 or other Alpha-9 HPV species. This study advances our understanding of humoral immune responses against HPV16 by providing insights about the influence of VLP antigen composition to measure humoral immune response against naturally acquired HPV infection.

Keywords: ELISA; HPV16 seroreactivity; Human papillomavirus; IgG antibodies; natural infection; virus-like particles.

MeSH terms

  • Adult
  • Antibodies, Viral / blood
  • Brazil
  • Capsid / immunology
  • Capsid Proteins / genetics
  • Cervix Uteri / virology
  • Cohort Studies
  • Female
  • Human papillomavirus 16 / genetics*
  • Human papillomavirus 16 / immunology*
  • Human papillomavirus 16 / pathogenicity
  • Humans
  • Leukocyte L1 Antigen Complex / immunology
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / immunology
  • Papillomaviridae / genetics
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / immunology
  • Uterine Cervical Neoplasms / etiology
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / virology
  • Viral Load / methods
  • Virion / immunology


  • Antibodies, Viral
  • Capsid Proteins
  • Leukocyte L1 Antigen Complex
  • Oncogene Proteins, Viral