title: Human papillomavirus infection with multiple types: pattern of coinfection and risk of cervical disease.
abstract: OBJECTIVE
  We investigated coinfection patterns for 25 human papillomavirus (HPV) types and assessed the risk conferred by multiple HPV types toward cervical disease.
  
  
  METHODS
  Sexually active women (n=5,871) in the NCI-sponsored Costa Rica HPV Vaccine Trial's prevaccination enrollment visit were analyzed. Genotyping for 25 HPVs was performed using SPF(10)/LiPA(25). We calculated odds ratios (ORs) to assess coinfection patterns for each genotype with 24 other genotypes. These ORs were pooled and compared with pair-specific ORs to identify genotype combinations that deviated from the pooled OR. We compared risk of CIN2+/HSIL+between multiple and single infections and assessed additive statistical interactions.
  
  
  RESULTS
  Of the 2478 HPV-positive women, 1070 (43.2%) were infected with multiple types. Multiple infections occurred significantly more frequently than predicted by chance. However, this affinity to be involved in a coinfection (pooled OR for 300 type-type combinations=2.2; 95% confidence interval [CI]=2.1-2.4) was not different across HPV type-type combinations. Compared with single infections, coinfection with multiple α9 species was associated with significantly increased risk of CIN2+(OR=2.2; 95% CI=1.1-4.6) and HSIL+(OR=1.6; 95% CI=1.1-2.4). However, disease risk was similar to the sum of estimated risk from individual types, with little evidence for synergistic interactions.
  
  
  CONCLUSIONS
  Coinfecting HPV genotypes occur at random and lead to cervical disease independently.
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Blvd, EPS 7072. Rockville, MD 20852, USA. chaturva@mail.nih.gov
authors.forename: Anil K
authors.initials: AK
authors.lastname: Chaturvedi
authors.forename: Hormuzd A
authors.initials: HA
authors.lastname: Katki
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.forename: Ana Cecilia
authors.initials: AC
authors.lastname: Rodríguez
authors.forename: Wim
authors.initials: W
authors.lastname: Quint
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Leen-Jan
authors.initials: LJ
authors.lastname: Van Doorn
authors.forename: Carolina
authors.initials: C
authors.lastname: Porras
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: Rolando
authors.initials: R
authors.lastname: Herrero
mesh_terms: D000293:Adolescent; D000328:Adult; D002584:Cervix Uteri / Q000821:virology*; D003364:Costa Rica / Q000453:epidemiology; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D015994:Incidence; D027383:Papillomaviridae / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications / Q000453:epidemiology* / Q000821:virology*; D018570:Risk Assessment; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology* / Q000821:virology; D055815:Young Adult
chemical_list: D004279:DNA, Viral