title: Molecular variants of human papillomavirus types 16 and 18 preferentially associated with cervical neoplasia.
abstract: In order to determine geographically related intratypic variation in human papillomavirus (HPV) type 16 and 18 isolates that could be associated with lesion development, data were analysed from an ongoing cohort study of the natural course of infection of HPVs and cervical neoplasia. Testing for HPVs was carried out by PCR and molecular variants of these HPVs were characterized by sequence analysis of the long control region and by dot blot hybridization of the E6 and L1 genes. Tests for HPV were done in multiple first-year specimens from 1690 women enrolled in a cancer screening program from 1993 to 1997. Subjects were followed-up by cytology and cervicography for detection of cervical lesions. Seven variants of HPV-16 and four of HPV-18 were detected in one or more specimens from 65 subjects. The same variant was found in specimens taken on different visits from each case of persistent infection. Overall, non-European variants tended to persist more frequently [odds ratio (OR)=4.5; 95% confidence interval (CI), 1.6-12.4] than European (E) variants (OR=2.5; 95% CI, 1.3-4.9), relative to the risk of persistence for non-oncogenic HPVs. In addition, non-E variants were more strongly associated with risk of both prevalent (age- and race-adjusted OR=172.2; 95% CI, 47.1-630.1) and incident [relative risk (RR)=22.5; 95% CI, 6.0-83.9] high-grade lesions than E variants (prevalent lesions OR=46.3; 95% CI, 15.5-138.0 and incident lesons RR=6.1; 95% CI, 1.3-27.4), relative to the risk for HPV-negative women. Although consistent, the latter differences were not statistically significant. If confirmed in other populations, measurement of intratypic variation of HPV-16 and -18 has the potential to serve as an ancillary tool in cervical cancer screening.
authors.affiliation: Department of Virology, Ludwig Institute for Cancer Research, R. Prof. Antonio Prudente 109, 4 Andar, 01509-010 São Paulo, SP, Brazil1.
authors.forename: Luisa L
authors.initials: LL
authors.lastname: Villa
authors.affiliation: Department of Biochemistry, Chemistry Institute5 and Department of Microbiology6, University of São Paulo, Cidade Universitária, São Paulo, CP20.780, Brazil.|Department of Virology, Ludwig Institute for Cancer Research, R. Prof. Antonio Prudente 109, 4 Andar, 01509-010 São Paulo, SP, Brazil1.
authors.forename: Laura
authors.initials: L
authors.lastname: Sichero
authors.affiliation: Department of Biochemistry, Chemistry Institute5 and Department of Microbiology6, University of São Paulo, Cidade Universitária, São Paulo, CP20.780, Brazil.|Department of Virology, Ludwig Institute for Cancer Research, R. Prof. Antonio Prudente 109, 4 Andar, 01509-010 São Paulo, SP, Brazil1.
authors.forename: Paula
authors.initials: P
authors.lastname: Rahal
authors.affiliation: Department of Biochemistry, Chemistry Institute5 and Department of Microbiology6, University of São Paulo, Cidade Universitária, São Paulo, CP20.780, Brazil.|Department of Virology, Ludwig Institute for Cancer Research, R. Prof. Antonio Prudente 109, 4 Andar, 01509-010 São Paulo, SP, Brazil1.
authors.forename: Otavia
authors.initials: O
authors.lastname: Caballero
authors.affiliation: Department of Pathology, Jewish General Hospital, 3755 Cote-Ste-Catherine Road, Montreal, CanadaH3T 1E22.
authors.forename: Alex
authors.initials: A
authors.lastname: Ferenczy
authors.affiliation: Public Health Sciences Department, University of Toronto, 12 Queen's Park Crescent West, Toronto, Ontario, CanadaM5S 1A83.
authors.forename: Tom
authors.initials: T
authors.lastname: Rohan
authors.affiliation: Departments of Epidemiology and Oncology, McGill University, 546 Pine Avenue West, Montreal, CanadaH2W 1S64.
authors.forename: Eduardo L
authors.initials: EL
authors.lastname: Franco
mesh_terms: D000367:Age Factors; D001483:Base Sequence; D001938:Brazil; D015331:Cohort Studies; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005814:Genes, Viral / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008403:Mass Screening; D009154:Mutation / Q000235:genetics; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D030361:Papillomavirus Infections / Q000150:complications* / Q000473:pathology / Q000821:virology; D016133:Polymerase Chain Reaction; D044469:Racial Groups; D017422:Sequence Analysis, DNA; D014412:Tumor Virus Infections / Q000150:complications* / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000150:complications* / Q000473:pathology / Q000821:virology*; D019562:Viral Load
chemical_list: D004279:DNA, Viral