RESUMEN
In cervical cancer, human papillomavirus type 18 (HPV 18) and HPV 16 are predominantly related to adenocarcinomas (ADCs) and squamous cell carcinomas (SCCs), respectively. Here, we studied whether the geographically distributed HPV intratypic variants are also associated with histologically different tumors. A total of 44 HPV 18-positive and 91 HPV 16-positive cervical carcinomas from Indonesian, Surinamese and Dutch patients were histologically classified using hematoxilin and eosin, periodic acid Schiff plus and Alcian Blue staining. Samples were sequenced and intratypic variants were classified into the known phylogenetic branches. The Asian Amerindian HPV 18 variant was observed in 56% of ADCs compared to 15% of SCCs (p < 0.006). The African HPV 18 variant was exclusively found in SCCs. By sequencing the HPV 18 E6 and E7 open reading frames, we found predicted amino acid changes only in 8 samples. Two amino acid changes were consistent throughout the African branch. In HPV 16-positive tumors, we did not find a specific linkage between intratypic variants and histopathology. We conclude that HPV 18 intratypic variants are differentially associated with adenocarcinoma and squamous cell carcinoma of the cervix. The findings described here stress the biologic significance of intratypic HPV variants and might help explaining differences in the pathogenesis of cervical ADCs and SCCs.
Asunto(s)
Adenocarcinoma/epidemiología , Adenocarcinoma/virología , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/virología , Proteínas de Unión al ADN/genética , Proteínas Oncogénicas Virales/genética , Papillomaviridae/genética , Papillomaviridae/patogenicidad , Polimorfismo Genético , Proteínas Represoras/genética , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Adenocarcinoma/etiología , Secuencia de Bases , Carcinoma de Células Escamosas/etiología , ADN Viral/análisis , Femenino , Geografía , Humanos , Incidencia , Indonesia/epidemiología , Datos de Secuencia Molecular , Países Bajos/epidemiología , Proteínas E7 de Papillomavirus , Filogenia , Análisis de Secuencia de ADN , Suriname/epidemiología , Neoplasias del Cuello Uterino/etiologíaRESUMEN
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. CONCLUSION: 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.