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The role of human papillomavirus type 16 and the fragile histidine triad gene in the outcome of cervical neoplastic lesions.

ABSTRACT: The presence of high-risk human papillomavirus, loss of heterozygosity on chromosome 3p and fragile histidine triad gene expression were assessed as potential markers of cancer and CIN progression in 83 cervical cancers and 74 cervical intraepithelial neoplasia grade 1 lesions. Human papillomavirus type 16 was an indicator of vascular involvement in cancers. Loss of heterozygosity, especially in the fragile histidine triad gene intron 5, was an indicator of high-grade tumours, greater tumour depth and lymph node involvement. Abnormal fragile histidine triad gene expression was more frequent in cervical intraepithelial neoplasia grade 1 lesions with increased risk of disease progression.

SUBMITTER: Terry G

PROVIDER: S-EPMC2409782 | biostudies-literature | 2004 Dec

REPOSITORIES: biostudies-literature

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The role of human papillomavirus type 16 and the fragile histidine triad gene in the outcome of cervical neoplastic lesions.

Terry G G Ho L L Londesborough P P Cross P P Lopes A A Monaghan J J Cuzick J J

British journal of cancer 20041201 12

The presence of high-risk human papillomavirus, loss of heterozygosity on chromosome 3p and fragile histidine triad gene expression were assessed as potential markers of cancer and CIN progression in 83 cervical cancers and 74 cervical intraepithelial neoplasia grade 1 lesions. Human papillomavirus type 16 was an indicator of vascular involvement in cancers. Loss of heterozygosity, especially in the fragile histidine triad gene intron 5, was an indicator of high-grade tumours, greater tumour dep ...[more]

PMID: 15570308

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Project description:HPV 16 is the cause of cervical carcinoma, but only a small fraction of women with HPV infection progress to this pathology. Besides persistent infection and HPV integration, several studies have suggested that HPV intratype variants may contribute to the development of cancer. The purpose of this study was to investigate the nucleotide variability and phylogenetically classify HPV 16 E6 variants circulating over a period of 16 years in women from Southern Mexico, and to analyze its association with precursor lesions and cervical carcinoma.This study was conducted in 330 cervical DNA samples with HPV 16 from women who were residents of the State of Guerrero, located in Southern Mexico. According of cytological and/or histological diagnosis, samples were divided into the following four groups: no intraepithelial lesion (n?=?97), low-grade squamous intraepithelial lesion (n?=?123), high-grade squamous intraepithelial lesion (n?=?19) and cervical carcinoma (n?=?91). HPV 16 E6 gene was amplified, sequenced and aligned with reference sequence (HPV 16R) and a phylogenetic tree was constructed to identify and classify HPV 16 variants. Chi squared was used and data analysis and statistics were done with SPSS Statistics and STATA softwares.Twenty seven HPV 16 E6 variants were detected in women from Southern Mexico, 82.12% belonged to the EUR, 17.58% to AA1 and 0.3% to Afr2a sublineages. The most common was E-G350 (40%), followed by E-prototype (13.03%), E-C188/G350 (11.82%), AA-a (10.61%), AA-c (6.07%) and E-A176/G350 (5.15%). Eight new E6 variants were found and 2 of them lead to amino acid change: E-C183/G350 (I27T) and E-C306/G350 (K68T). The HPV 16 variant that showed the greatest risk of leading to the development of CC was AA-a (OR?=?69.01, CI?=?7.57-628.96), followed by E-A176/G350 (OR?=?39.82, CI?=?4.11-386.04), AA-c (OR?=?21.16, CI 2.59-172.56), E-G350 (OR?=?13.25, CI?=?2.02-87.12) and E-C188/G350 (OR?=?10.48, CI?=?1.39-78.92).The variants more frequently found in women with cervical carcinoma are E-G350, AA-a, AA-c, E-C188/G350 and E-A176/G350. All of them are associated with the development of cervical carcinoma, however, AA-a showed the highest association. This study reinforces the proposal that HPV 16 AA-a is an oncogenic risk for cervical carcinoma progression in Mexico.

Dataset Information

The role of human papillomavirus type 16 and the fragile histidine triad gene in the outcome of cervical neoplastic lesions.

Publications

The role of human papillomavirus type 16 and the fragile histidine triad gene in the outcome of cervical neoplastic lesions.

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