title: Association of HPV16 E6 variants with diagnostic severity in cervical cytology samples of 354 women in a US population.
abstract: It has been suggested that DNA sequence variants of HPV16 contribute to differences in the behavior of individual cervical lesions. To address this question, we have analyzed the association of HPV16 variants with diagnostic severity in 354 HPV16-positive Oklahoman women. HPV16 variant status was determined by PCR amplification and DNA sequencing of the E6 open reading frame. European sequences were identified in 86% of samples and 14% were non-European. Of the 51 non-European cases, 61% were Asian-American, 23% African and 16% were Native American variants. European prototype and related variants were present in comparable numbers (43% each) but the relative proportion of each differed with diagnostic category. In general, the proportion of European variants and non-European variants increased with diagnostic severity while the European prototype decreased. When adjusted for age and race (white, black or Hispanic), the increased risk for carcinoma/severe dysplasia for non-European variants was statistically significant with an odds ratio of 3.8 (1.3-10.7). However, the analogous comparison for the European variants, although also showing increased association with carcinoma/severe dysplasia, did not reach statistical significance (OR = 1.6 (95% CI 0.7-3.6). Overall, HPV16 European sequences (both prototype and related variants), were predominant in Oklahoman women including those with cancers. This suggests that while there appear to be differences among the HPV16-variant categories in risk for progression to invasive cancer, all variant categories are associated with the development of invasive cancer.
authors: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors: Rosemary E
authors: RE
authors: Zuna
authors: William E
authors: WE
authors: Moore
authors: Rebecca P
authors: RP
authors: Shanesmith
authors: S Terence
authors: ST
authors: Dunn
authors: Sophia S
authors: SS
authors: Wang
authors: Mark
authors: M
authors: Schiffman
authors: Gregory L
authors: GL
authors: Blakey
authors: Travis
authors: T
authors: Teel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003581:Cytodiagnosis; D004273:DNA, Neoplasm / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D052161:Human papillomavirus 18 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D030361:Papillomavirus Infections / Q000821:virology*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics*; D014481:United States; D002583:Uterine Cervical Neoplasms / Q000821:virology*; D014626:Vaginal Smears; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000821:virology*
chemical_list: D004273:DNA, Neoplasm; D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins