Unique variants of human papillomavirus genotypes 52 and 58 and risk of cervical neoplasia

Abstract

Human papillomavirus (HPV) 52 and 58 are oncogenic HPV types prevalent in Asia. Our study aims to explore intratypic variants of HPV 52 and 58 in Taiwan. A total of 11,923 women were enrolled from seven townships in [1991][1992]. HPV DNA in their cervical cells was detected and typed by EasyChip V R HPV blot. Among 424 participants infected with HPV 52 and/or 58, nucleotide variations were determined in cervical cell samples of 406 participants by the polymerase chain reaction sequencing of the long control region, E6 and E7 genes. Nonprototype-like variants including lineages B and C were detected in 278 (99.3%) of 280 HPV 52 samples. The prototype and prototype-like group (lineage A) of HPV58 was found in 132 (98.5%) of 134 HPV 58 samples, with sublineage A1, A2 and A3 variant in 14.2, 27.6 and 56.7%, respectively. Among women infected with single HPV 52 type, the C variant (vs. B variant) was associated with an increased prevalence of cytologically diagnosed high-grade squamous intraepithelial lesion or worse lesions showing an age-adjusted odds ratio (95% confidence interval, CI) of 5.2 (1.0-27.6) and an increased prevalence of histologically confirmed high-grade cervical intraepithelial neoplasia or more severe lesions with an age-adjusted odds ratio (95% CI) of 7.6 (1.3-43.8). It was concluded that frequency distributions of HPV 52 and 58 variants in Taiwan were different from those in European and American populations. The association between C variant of HPV 52 and prevalence of cervical neoplasia needs further validation.Oncogenic human papillomavirus (HPV) is the major cause of cervical cancer. In addition to HPV 16 and 18, HPV 52 and 58 are also considered high-risk types for cervical intraepithelial lesions (CINs) and invasive carcinoma. 1,2 The unusually high prevalence of HPV 52 and 58 has been reported in Chinese populations living in China 3,4 and Taiwan. [5][6][7][8] In a previous report of our study, the prevalence of high-grade squamous intraepithelial lesion (HSIL) or worse lesions among participants with single-type infection of HPV 16, HPV 58 and HPV 52 at study entry was 31.9, 35.7 and 13.3%, respectively. 9 The participants infected with HPV 16, HPV 58 or HPV 52 had an increased prevalence of cervical cancer and carcinoma in situ (CIS).Intratypic HPV variants are characterized by the difference of less than 2% in nucleotide sequence from the prototypic L1 gene. 10 The genetic divergence among variants can differ by as much as 5% in the noncoding long control region (LCR). 11 But a study based on the complete genome analyses of HPV 16 showed that the E5-L2 intergenic region and the E4 and E5 genes are also hypervariable. 12 In a recent study, HPV variants can be classified based on their nucleotide sequence differences with most variants differing by <3%; type-specific variant lineages are defined based on a complete genome nucleotide sequence having >1% dissimilarity with the prototype and are named according to the phylogenetic tree topologies for each individual type. 13 Previous studie...

Differential In Vitro Immortalization Capacity of Eleven, Probable High-Risk Human Papillomavirus Types

“…The E6 K93R variant in our construct is present in 98% of the HPV52-positive cervical cancers in Japan (39,40,56) and has been significantly associated with an increased CIN2/3 risk, suggesting that it represents a carcinogenic variant (57), yet the findings that p53 expression levels were unaltered and immortalization was unsuccessful in our hands indicate that this highly common variant is not as oncogenic as other hrHPV types, at least in a Caucasian genetic background. HPV59, which is less prevalent in invasive cervical cancers (7), showed a better immortalization capacity.…”

“…HPV52 was also amplified from a full-length HPV plasmid and contained a sequence variation in E6 (K93R). This HPV52 variant has frequently been detected in cervical cancers in Asia (39,40). HPV51 and HPV59 E6/E7 were cloned from cervical scrapes, and HPV70 was cloned from a tumor sample.…”

Genetic Variability in E6 and E7 Oncogenes from Human Papillomavirus Type 58 in Mexican Women

“…It is worth noticing that this cited study included 2 samples from Mexico. They hypothesized that lineage A (probably sublineage A2) was the oldest lineage, which disseminated with early human evolution and assigned A1 to the sublineage that contained the prototype, being rarely detected except in Asia [38]. The geographical origin of the sequences shows a somehow even distribution of the Yucatan sequences along the trees obtained; all sequences were A lineage in E6 and E7, and a large proportion closely related to A1 sublineage.…”

“…In contrast to HPV16 geographic definition of the variants, and their more convincing association with disease (reviewed by Burk et al [30]), in the case of HPV58, the studies have been complicated by the heterogeneity of the sequences and their distribution worldwide [29,38,39].…”

“…Calleja-Macias et al [22] analyzed the LCR region and defined 21 variants without any geographical association. Later, a study by Chan et al [38] used concatenated sequences of E6-E7-E2-E5-L1-LCR showing a limited geographic correlation for HPV-58 lineages distribution, where lineage A was the most generally distributed, with sublineages A1, and A3 present in higher frequencies in Asia, while sublineage A2 was more predominant in Africa, the Americas, and, Europe. It is worth noticing that this cited study included 2 samples from Mexico.…”