title: Viral load in the natural history of human papillomavirus type 16 infection: a nested case-control study.
abstract: BACKGROUND
  Viral load may influence the course of human papillomavirus type 16 (HPV-16) infection.
  
  
  METHODS
  This case-control study was nested within the 2-year Atypical Squamous Cells of Undetermined Significance and Low-Grade Squamous Intraepithelial Lesion Triage Study, in which women were followed semiannually for HPV and cervical intraepithelial neoplasia (CIN). Case patients (n = 62) were women diagnosed with CIN3 following HPV-16-positive detection at a follow-up visit. HPV-16-positive controls (n = 152) without CIN2 or CIN3 were matched to cases based on the follow-up visit in which viral load was measured. Real-time polymerase chain reaction was used for HPV-16 DNA quantification.
  
  
  RESULTS
  The risk of CIN3 increased with increasing HPV-16 DNA load at the follow-up visit (odds ratio, 1.63; 95% confidence interval, 1.33-1.99 per 1 log(10) unit increase); the association was not affected by whether HPV-16 was present at enrollment. When HPV-16 was present at both enrollment and follow-up, viral load remained high among cases (P = .77) but decreased substantially among controls (P = .004). Among women with HPV-16 found initially during follow-up, viral load in the first HPV-16-positive sample was associated with short-term persistence; load was higher in those with infection, compared with those without infection, 1 visit after the initial positivity (P = .001).
  
  
  CONCLUSIONS
  Viral load of newly detected infections and changes in viral load predict persistence and progression of HPV-16 infections.
authors.affiliation: Department of Pathology, School of Medicine, University of Washington, Seattle, Washington, USA. longfu@u.washington.edu
authors.forename: Long Fu
authors.initials: LF
authors.lastname: Xi
authors.forename: James P
authors.initials: JP
authors.lastname: Hughes
authors.forename: Philip E
authors.initials: PE
authors.lastname: Castle
authors.forename: Zoe R
authors.initials: ZR
authors.lastname: Edelstein
authors.forename: Chunhui
authors.initials: C
authors.lastname: Wang
authors.forename: Denise A
authors.initials: DA
authors.lastname: Galloway
authors.forename: Laura A
authors.initials: LA
authors.lastname: Koutsky
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Kiviat
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D052162:Human papillomavirus 16; D006801:Humans; D008137:Longitudinal Studies; D016017:Odds Ratio; D030361:Papillomavirus Infections / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000821:virology*; D019562:Viral Load; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000821:virology*
chemical_list: D004279:DNA, Viral