Risk of HPV-16/18 Infections and Associated Cervical Abnormalities in Women Seropositive for Naturally Acquired Antibodies: Pooled Analysis Based on Control Arms of Two Large Clinical Trials

J Infect Dis. 2018 Jun 5;218(1):84-94. doi: 10.1093/infdis/jiy112.


Background: Studies on the role of antibodies produced after infection with human papillomavirus 18 (HPV-18) and subsequent protection from HPV-18 infection have been conflicting, mainly due to inadequate sample size.

Methods: We pooled data from the control arms of the Costa Rica Vaccine Trial and the PATRICIA trial. Using Poisson regression we compared the risk of newly detected 1-time HPV-18 infection, HPV-18 1-year persistent infection (12MPI), and HPV-18-associated atypical squamous cells of undetermined significance or greater (ASC-US+) lesions between HPV-18 seropositive and seronegative women.

Results: High HPV-18 antibodies at enrollment was associated with reduced subsequent HPV-18 detection (P trend = 0.001; relative rate [RR] = 0.69; 95% confidence interval [CI], 0.47-1.01 for the third quartile; RR = 0.63; 95% CI, 0.43-0.94 for the fourth quartile, compared to seronegative). The risk of 12MPI showed a decreasing trend with increasing antibodies (P trend = 0.06; RR = 0.72; 95% CI, 0.29-1.77; RR = 0.42; 95% CI, 0.13-1.32 for the third and fourth quartiles, respectively). Lastly, we observed a significant decreased risk of HPV-18 ASC-US+ with increasing antibody (P trend = 0.01; RR = 0.46; 95% CI, 0.21-0.97 for the fourth quartile). We also observed a significant decreased risk of HPV-16 infection, 12MPI, and ASC-US+ with increasing HPV-16 antibody level.

Conclusions: High HPV-18 naturally acquired antibodies were associated with partial protection from future HPV-18 infections and associated lesions.

Clinical trials registration: NCT00128661 and NCT001226810.

Trial registration: ClinicalTrials.gov NCT00128661 NCT01226810.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood*
  • Carcinoma, Squamous Cell / epidemiology*
  • Carcinoma, Squamous Cell / virology
  • Costa Rica / epidemiology
  • Female
  • Human papillomavirus 16 / immunology*
  • Human papillomavirus 18 / immunology*
  • Humans
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / epidemiology*
  • Papillomavirus Infections / virology
  • Risk Assessment
  • Uterine Cervical Neoplasms / epidemiology*
  • Uterine Cervical Neoplasms / virology
  • Young Adult


  • Antibodies, Viral

Associated data

  • ClinicalTrials.gov/NCT00128661
  • ClinicalTrials.gov/NCT01226810