title: Geographical distribution and oncogenic risk association of human papillomavirus type 58 E6 and E7 sequence variations.
abstract: Human papillomavirus (HPV) 58 accounts for a notable proportion of cervical cancers in East Asia and parts of Latin America, but it is uncommon elsewhere. The reason for such ethnogeographical predilection is unknown. In our study, nucleotide sequences of E6 and E7 genes of 401 HPV58 isolates collected from 15 countries/cities across four continents were examined. Phylogenetic relationship, geographical distribution and risk association of nucleotide sequence variations were analyzed. We found that the E6 genes of HPV58 variants were more conserved than E7. Thus, E6 is a more appropriate target for type-specific detection, whereas E7 is more appropriate for strain differentiation. The frequency of sequence variation varied geographically. Africa had significantly more isolates with E6-367A (D86E) but significantly less isolates with E6-203G, -245G, -367C (prototype-like) than other regions (p ≤ 0.003). E7-632T, -760A (T20I, G63S) was more frequently found in Asia, and E7-793G (T74A) was more frequent in Africa (p < 0.001). Variants with T20I and G63S substitutions at E7 conferred a significantly higher risk for cervical intraepithelial neoplasia grade III and invasive cervical cancer compared to other HPV58 variants (odds ratio = 4.44, p = 0.007). In conclusion, T20I and/or G63S substitution(s) at E7 of HPV58 is/are associated with a higher risk for cervical neoplasia. These substitutions are more commonly found in Asia and the Americas, which may account for the higher disease attribution of HPV58 in these areas.
authors.affiliation: Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. paulkschan@cuhk.edu.hk
authors.forename: Paul K S
authors.initials: PK
authors.lastname: Chan
authors.forename: Chuqing
authors.initials: C
authors.lastname: Zhang
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Park
authors.forename: Karen K
authors.initials: KK
authors.lastname: Smith-McCune
authors.forename: Joel M
authors.initials: JM
authors.lastname: Palefsky
authors.forename: Lucia
authors.initials: L
authors.lastname: Giovannelli
authors.forename: Francois
authors.initials: F
authors.lastname: Coutlée
authors.forename: Samantha
authors.initials: S
authors.lastname: Hibbitts
authors.forename: Ryo
authors.initials: R
authors.lastname: Konno
authors.forename: Wannapa
authors.initials: W
authors.lastname: Settheetham-Ishida
authors.forename: Tang-Yuan
authors.initials: TY
authors.lastname: Chu
authors.forename: Annabelle
authors.initials: A
authors.lastname: Ferrera
authors.forename: María
authors.initials: M
authors.lastname: Alejandra Picconi
authors.forename: Federico
authors.initials: F
authors.lastname: De Marco
authors.forename: Yin-Ling
authors.initials: YL
authors.lastname: Woo
authors.forename: Tainá
authors.initials: T
authors.lastname: Raiol
authors.forename: Patricia
authors.initials: P
authors.lastname: Piña-Sánchez
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Bae
authors.forename: Martin C S
authors.initials: MC
authors.lastname: Wong
authors.forename: Mike Z
authors.initials: MZ
authors.lastname: Chirenje
authors.forename: Tsitsi
authors.initials: T
authors.lastname: Magure
authors.forename: Anna-Barbara
authors.initials: AB
authors.lastname: Moscicki
authors.forename: Alison N
authors.initials: AN
authors.lastname: Fiander
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Capra
authors.forename: Eun
authors.initials: E
authors.lastname: Young Ki
authors.forename: Yi
authors.initials: Y
authors.lastname: Tan
authors.forename: Zigui
authors.initials: Z
authors.lastname: Chen
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burk
authors.forename: Martin C W
authors.initials: MC
authors.lastname: Chan
authors.forename: Tak-Hong
authors.initials: TH
authors.lastname: Cheung
authors.forename: David
authors.initials: D
authors.lastname: Pim
authors.forename: Lawrence
authors.initials: L
authors.lastname: Banks
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D036022:Capsid Proteins / Q000235:genetics*; D002584:Cervix Uteri / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation / Q000235:genetics*; D005843:Geography; D006801:Humans; D007390:International Agencies; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics; D050725:Papillomavirus E7 Proteins / Q000235:genetics*; D030361:Papillomavirus Infections / Q000235:genetics* / Q000821:virology; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011379:Prognosis; D018570:Risk Assessment; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D036022:Capsid Proteins; D004273:DNA, Neoplasm; C548991:E6 protein, human papillomavirus type 58; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins