title: Risk of precancer determined by HPV genotype combinations in women with minor cytologic abnormalities.
abstract: BACKGROUND
  Studies suggest that testing for individual human papillomavirus (HPV) genotypes can improve risk stratification in women with minor cytologic abnormalities. We evaluated genotyping for HPV16, HPV16/18, and HPV16/18/45 in carcinogenic HPV-positive women with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cytology.
  
  
  METHODS
  For women enrolled in the ASCUS-LSIL Triage Study (ALTS), we calculated the age-stratified (<30 and 30+ years) positivity and cumulative risk over two years of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) when testing positive or negative for three genotype combinations: HPV16, HPV16/18, and HPV16/18/45.
  
  
  RESULTS
  Among women with ASCUS cytology, HPV16 positivity was 17.1% and increased to 22.0% (P < 0.001) for HPV16/18 and 25.6% (P < 0.001) for HPV16/18/45. Among women with LSIL cytology, HPV16 positivity was 21.1% and increased to 30.0% (P < 0.001) for HPV16/18 and 34.0% (P = 0.017) for HPV16/18/45. Regardless of cytology and age group, the greatest risk difference between test positives and test negatives was observed for HPV16 with decreasing risk stratification for HPV16/18 and HPV16/18/45. However, testing negative for any of the three combinations while being positive for another carcinogenic type still implied a two-year risk of CIN3+ of 7.8% or more.
  
  
  CONCLUSIONS
  Although genotyping for HPV16, 18, and 45 provided additional risk stratification in carcinogenic HPV-positive women with minor cytologic abnormalities, the risk among genotype-negative women was still high enough to warrant immediate colposcopy referral.
  
  
  CONCLUSIONS
  HPV genotyping in HPV-positive women with minor cytologic abnormalities will likely not alter clinical management. Adding HPV45 to genotyping assays is not warranted.
authors.affiliation: Divisions of Cancer Epidemiology and Genetics and Cancer Prevention National Cancer Institute, Department of Health and Human Services, NIH, Bethesda, MD 20852, USA. gagej@mail.nih.gov
authors.forename: Julia C
authors.initials: JC
authors.lastname: Gage
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Diane
authors.initials: D
authors.lastname: Solomon
authors.forename: Cosette M
authors.initials: CM
authors.lastname: Wheeler
authors.forename: Patti E
authors.initials: PE
authors.lastname: Gravitt
authors.forename: Philip E
authors.initials: PE
authors.lastname: Castle
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003127:Colposcopy; D003581:Cytodiagnosis; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics* / Q000821:virology; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000175:diagnosis / Q000209:etiology*; D011379:Prognosis; D012307:Risk Factors; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000209:etiology*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000209:etiology*; D014626:Vaginal Smears; D055815:Young Adult
chemical_list: D004279:DNA, Viral