title: Molecular variants of human papilloma virus 16 E2, E4, E5, E6 and E7 genes associated with cervical neoplasia in Romanian patients.
abstract: The aim of this study was to identify and associate the sequence variations of human Papillomavirus 16 (HPV16) genes from women who live in two different areas of Romania and associate them with malignant progression. One hundred twenty-four HPV16-positive cervical isolates were collected, and the E2, E4, E5, E6 and E7 viral genes were sequenced. Two new missense mutations in the E6 gene (C279G and A305C) were found (together or alone, in association with other mutations) in 44 of 124 cases. The most frequently simultaneously mutated genes were E4/E2 hinge, E5 and E6 (p = 0.0004) in squamous cell carcinoma (SCC) samples. Also, for SCC patients, the best-correlated mutation patterns were obtained for E4/E2 hinge-E5 (r = 0.7984; p < 0.0001). No sample was found to have all of the investigated viral genes concurrently mutated. Phylogenetic analysis was performed to characterize the viral variants. Similar results were found for SCC and cervical intraepithelial neoplasia III (CINIII) cases. After all of the target gene sequences were assembled, all patients were found to be infected with viruses of the HPV16- European-German (EG) lineage, and two clusters were identified, the first (55/96 variants) from Moldavia and the second (41/96 variants) from Bucharest. The distinct cluster derived from EG in Moldavia could partially explain the increased frequency of SCC in this area. This study has generated a comprehensive set of sequence variation data on HPV16 circulating in Romania to join the existing data and highlight the important role of HPV16 variants during cervical carcinogenesis.
authors.affiliation: Molecular Virology Department, Stefan S. Nicolau Institute of Virology, 285 Mihai Bravu Avenue, Sector 3, 030304, PO 77, PO Box 201, Bucharest, Romania, adrianaplesa@yahoo.com.
authors.forename: Adriana
authors.initials: A
authors.lastname: Plesa
authors.forename: Gabriela
authors.initials: G
authors.lastname: Anton
authors.forename: Iulia V
authors.initials: IV
authors.lastname: Iancu
authors.forename: Carmen C
authors.initials: CC
authors.lastname: Diaconu
authors.forename: Irina
authors.initials: I
authors.lastname: Huica
authors.forename: Anca D
authors.initials: AD
authors.lastname: Stanescu
authors.forename: Demetra
authors.initials: D
authors.lastname: Socolov
authors.forename: Elena
authors.initials: E
authors.lastname: Nistor
authors.forename: Elena
authors.initials: E
authors.lastname: Popa
authors.forename: Mihai
authors.initials: M
authors.lastname: Stoian
authors.forename: Anca
authors.initials: A
authors.lastname: Botezatu
mesh_terms: D016000:Cluster Analysis; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D052162:Human papillomavirus 16 / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification*; D006801:Humans; D017720:Molecular Epidemiology; D030361:Papillomavirus Infections / Q000150:complications / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D010802:Phylogeny; D012383:Romania / Q000453:epidemiology; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D004279:DNA, Viral; D014764:Viral Proteins