Profile of physical status and gene variation of human papillomavirus 58 genome in cervical cancer

Abstract

Epidemiological studies have shown that human papillomavirus 58 (HPV 58) is found at a relatively high frequency in east Asia and some regions of Central and South America. To investigate the physical status of HPV 58 and analyse sequence variations of HPV 58 in cervical cancer patients, the HPV 58 genome in 37 HPV 58-positive cervical cancer specimens collected from China were investigated by a mapping analysis based on nested PCR and nucleotide sequencing. A pure integrated genome was found in 78.4 % (29/37) of specimens, which is much higher than that found in previous studies. Multiple disruptions were first found among the integrated HPV 58 genomes in 51.7 % (15/29) of specimens. Among the 7824 bp of the HPV 58 genome, 119 (1.52 %) nucleotide positions were found to be variable, and 45 of them lead to amino acid changes. Phylogenetic analyses, based on partial L1 sequences of 14 variants isolated in previous studies and this study, show that two main groups were observed in HPV 58 variants, the prototype or prototype-like group and the non-prototype-like group.

Determination of Integrated HPV58 Sequences in Cervical Lesions

“…8 The distribution of virus disruption sites in our study was consistent with that observation, with a range from nucleotide 1088 to 5057. Furthermore, considering the 2 main disrupted region discovered at E1 previously, the common disruption of the E1 gene in this study is no exception.…”

“…5 Integration of HPV16 and 18 was widely studied, and their integrated sequences were determined in cell lines and clinical samples. 6 In addition, integration of HPV58 was identified in many infected patients with real-time polymerase chain reaction (PCR) by measuring the ratio of E2 to either E6 or E7 loads, 7,8 or with nested PCR with primer sets covering the whole HPV58 genome 9 ; however, owing to the limitations of those indirect methods, no viral-cellular junction could be identified. Likewise, there was no sequence information of viral disruption site and integration sites for HPV58.…”

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

“…13 HPV 58 in our study showed variant lineages similar to those reported by previous studies. 19,20,22,23 HPV 58 C variant, a nonprototype variant in our study, could be found in eight (3.6%) of 220 HPV 58 samples in Hong Kong, 20 but not detected in 37 HPV 58 samples in Chengdu, China. 22 In Japan, the nonprototype of HPV 58 was observed in only one of 41 HPV 58 samples.…”

“…19,20,22,23 HPV 58 C variant, a nonprototype variant in our study, could be found in eight (3.6%) of 220 HPV 58 samples in Hong Kong, 20 but not detected in 37 HPV 58 samples in Chengdu, China. 22 In Japan, the nonprototype of HPV 58 was observed in only one of 41 HPV 58 samples. 23 In our study, nucleotide variations at positions 632 and 760 of HPV 58, resulting in amino acid change of T20I and G63S in E7, were linked in lineage A3.…”

“…16,17 The intratypic variants of HPV 16 and 18 have been studied extensively, and data on the E6, E7 and LCR genetic variations of HPV 52 or 58 have also been reported previously. [18][19][20][21][22][23] Variant lineages of carcinogenic HPV types were determined (RD Burk; personal communication) in a population-based prospective study and their associations with viral persistence and/or risk of CIN3/ CIS and cancer (CIN3þ) were evaluated using a nested casecontrol study design. 13 However, data concerning the associations between variants of HPV 52 or 58 and persistent infection of HPV or cervical neoplasia were still limited.…”