title: Evaluation of the polyclonal ELISA HPV serology assay as a biomarker for human papillomavirus exposure.
abstract: BACKGROUND
  Seropositivity to human papillomavirus (HPV)16 and 18 antibodies is used as a measure of cumulative HPV exposure and as a stratifier of HPV exposure for vaccine efficacy analyses. Overall performance of these assays, as a measure of HPV exposure, has not been evaluated.
  
  
  METHODS
  Using data from the enrollment phase of the HPV16/18 vaccine trial in Costa Rica, we evaluated the performance of the polyclonal enzyme-linked immunosorbent assay (ELISA) HPV16 and 18 serological assays as a measure of HPV exposure. Biologic (e.g., HPV infection at the cervix) and behavioral characteristics (e.g., lifetime number of sexual partners) with known associations with current and past HPV infection were used to define cases and controls (HPV exposed vs. not exposed). Prevaccination serum was measured for antibodies against HPV16 and 18 by ELISA; cervical samples were tested for HPV DNA using PCR SPF10/LiPA25. ELISA results were analyzed using receiver-operator characteristic curves; performance was evaluated at the manufacturer set cut point (HPV16 = 8, HPV18 = 7) and at cut points chosen to optimize sensitivity and specificity (HPV16 = 34, HPV18 = 60).
  
  
  RESULTS
  Defining cases as type-specific HPV DNA positive with high-grade abnormal cytology (i.e., combined molecular and microscopic markers of infection), HPV16-ELISA gave sensitivity that was lower at the optimal cut point than the manufacturer cut point (62.2 compared with 75.7, respectively; P = 0.44). However, specificity was higher (85.3 compared with 70.4, respectively; P < 0.0001). Similarly, HPV18-ELISA gave sensitivity that was lower at the optimal cut point than the manufacturer cut point (34.5 compared with 51.7, respectively; P = 0.40), with higher specificities (94.9 compared with 72.6, respectively; P < 0.0001).
  
  
  CONCLUSIONS
  Modifying cut points did not improve the low sensitivity. The low sensitivity of this assay does not support its use for risk stratification or clinical settings.
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20852, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Coseo
authors.forename: Carolina
authors.initials: C
authors.lastname: Porras
authors.forename: Lori E
authors.initials: LE
authors.lastname: Dodd
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.forename: Ana Cecilia
authors.initials: AC
authors.lastname: Rodriguez
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.forename: Paula
authors.initials: P
authors.lastname: Gonzalez
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.forename: Silvia
authors.initials: S
authors.lastname: Jimenez
authors.forename: Diane
authors.initials: D
authors.lastname: Solomon
authors.forename: Catherine
authors.initials: C
authors.lastname: Bougelet
authors.forename: Leen-Jan
authors.initials: LJ
authors.lastname: van Doorn
authors.forename: Wim
authors.initials: W
authors.lastname: Quint
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Safaeian
mesh_terms: D000914:Antibodies, Viral / Q000097:blood*; D015415:Biomarkers; D016001:Confidence Intervals; D003364:Costa Rica; D004279:DNA, Viral / Q000302:isolation & purification; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods / Q000592:standards*; D005260:Female; D052162:Human papillomavirus 16 / Q000145:classification / Q000235:genetics / Q000276:immunology; D052161:Human papillomavirus 18 / Q000145:classification / Q000235:genetics / Q000276:immunology; D006801:Humans; D015999:Multivariate Analysis; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics / Q000276:immunology*; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D053918:Papillomavirus Vaccines; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D004279:DNA, Viral; D053918:Papillomavirus Vaccines