Human papillomavirus type 16 E6, E7, and L1 variants in cervical cancer in Indonesia, Suriname, and The Netherlands.
OBJECTIVE
Human papillomavirus type 16 (HPV 16) has several intratypic variants, and some are associated with enhanced oncogenic potential. For risk determination as well as for future vaccine development, knowledge about variants is important. Regarding the geographical distribution of HPV variants and the lack of data from Indonesia and Suriname, we studied the prevalence of HPV 16 variants in cervical cancer in these high incidence countries. Data were compared with The Netherlands, a low-risk country.


METHODS
DNA samples from 74 formalin-fixed paraffin-embedded HPV 16-positive cervical carcinomas from Indonesia (Java, N = 22), Suriname (N = 25), and The Netherlands (N = 27) were amplified using primers specific for the E6, E7, and part of the L1 regions. Products were sequenced and analyzed.


RESULTS
A specific Javanese variant, with mutations 666A in E7 and 6826T in L1, was found in 73% of the Indonesian samples, 56% having an additional mutation in the E6 open reading frame (ORF; 276G), giving the predicted amino acid change N58S. This Javanese variant was also found in three Surinamese samples, which reflects what could be expected from migration of Javanese people to Surinam. Other non-European variants were identified in Indonesian, Surinamese, and Dutch samples in 14%, 28%, and 19%, respectively.


CONCLUSIONS
The majority of the HPV 16-positive cervical cancers in Indonesia are caused by a specific intratypic variant that was rarely found before in other countries.
Department of Gynecology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands. M.A.de_boer@LUMC.nl
Marjon A
MA
de Boer
Lex A W
LA
Peters
Mohammed Farid
MF
Aziz
Budiningsih
B
Siregar
Santoso
S
Cornain
M Albert
MA
Vrede
Ekaterina S
ES
Jordanova
Sandra
S
Kolkman-Uljee
Gert Jan
GJ
Fleuren
D001483:Base Sequence; D036022:Capsid Proteins; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006801:Humans; D007214:Indonesia / Q000453:epidemiology; D009426:Netherlands / Q000453:epidemiology; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000145:classification* / Q000235:genetics; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000150:complications / Q000453:epidemiology / Q000821:virology*; D012097:Repressor Proteins; D013532:Suriname / Q000453:epidemiology; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000821:virology*
D036022:Capsid Proteins; D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; C063317:L1 protein, Human papillomavirus type 16