Dataset Information

HPV-16 E2 gene disruption and sequence variation in CIN 3 lesions and invasive squamous cell carcinomas of the cervix: relation to numerical chromosome abnormalities.

ABSTRACT:

Aim

To test the hypothesis that, because the human papillomavirus (HPV) E2 protein represses viral early gene transcription, E2 gene sequence variation or disruption could play a part in the induction of the numerical chromosome abnormalities that have been described in squamous cervical lesions.

Methods

The integrity and sequence of the E2 gene from 11 cervical intraepithelial neoplasia (CIN) grade 3 lesions and 14 invasive squamous cell carcinomas, all of which contained HPV-16, were analysed by the polymerase chain reaction (PCR). The E2 gene was amplified in three overlapping fragments and PCR products sequenced directly. Chromosome abnormalities were identified by interphase cytogenetics using chromosome specific probes for chromosomes 1, 3, 11, 17, 18, and X.

Results

E2 gene disruption was present in significantly more invasive carcinomas (eight of 14) than CIN 3 lesions (one of 11) (p = 0.03). No association was found between E2 disruption and the presence of a numerical chromosome abnormality. The E2 gene from the non-disrupted isolates was sequenced and wild-type (n = 5) and variant (n = 11) sequences identified. Variant sequences belonged to European and African classes and contained from one to 15 amino acid substitutions. Although numerical chromosome abnormalities were significantly more frequent in invasive squamous cell carcinoma than CIN 3 (p = 0.04), there was no significant relation between the presence of sequence variation and either histological diagnosis or chromosome abnormality.

Conclusions

These data do not support the hypothesis that E2 gene disruption or variation is important in the induction of chromosome imbalance in these lesions. However, there is a relation between E2 gene disruption and the presence of invasive disease.

SUBMITTER: Graham DA

PROVIDER: S-EPMC1186970 | biostudies-literature | 2000 Aug

REPOSITORIES: biostudies-literature

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Publications

HPV-16 E2 gene disruption and sequence variation in CIN 3 lesions and invasive squamous cell carcinomas of the cervix: relation to numerical chromosome abnormalities.

Graham D A DA Herrington C S CS

Molecular pathology : MP 20000801 4

<h4>Aim</h4>To test the hypothesis that, because the human papillomavirus (HPV) E2 protein represses viral early gene transcription, E2 gene sequence variation or disruption could play a part in the induction of the numerical chromosome abnormalities that have been described in squamous cervical lesions.<h4>Methods</h4>The integrity and sequence of the E2 gene from 11 cervical intraepithelial neoplasia (CIN) grade 3 lesions and 14 invasive squamous cell carcinomas, all of which contained HPV-16, ...[more]

PMID: 11040943

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Project description:ObjectivesWe aim to assess the efficacy and safety of therapeutic human papillomavirus (HPV) vaccines to treat cervical intraepithelial neoplasia of grade 2 or 3 (CIN 2/3).DesignSystematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.Data sourcesPubMed, Embase, Web of Science, Global Index Medicus and CENTRAL Cochrane were searched up to 31 January 2022.Eligibility criteriaPhase II/III randomised controlled trials (RCTs) and single-arm studies reporting the efficacy of therapeutic vaccines to achieve regression of CIN 2/3 lesions were included. Studies evaluating only safety and side effects of the vaccine were excluded.Data extraction and synthesisTwo independent reviewers extracted data and evaluated study quality. A random-effect model was used to pool the proportions of regression and/or HPV clearance.Results12 trials met the inclusion criteria. Out of 734 women (all studies considered) receiving therapeutic HPV vaccine for CIN 2/3, 414 regressed to normal/CIN 1 with an overall proportion of regression of 0.54 (95% CI 0.39 to 0.69) for vaccinated group; 166 women (from five RCTs) receiving placebo only achieving a pooled normal/CIN 1 regression of 0.27 (95% CI 0.20 to 0.34). When including only the five two-arm studies, the regression proportion for the 410 vaccine group participants was higher than that of the 166 control group participants (relative risk (RR) 1.52; 95% CI 1.14 to 2.04). The pooled proportion of high-risk human papillomavirus (hrHPV) clearance was 0.42 (95% CI 0.32 to 0.52) in the vaccine group (six studies with a total of 357 participants) and 0.17 (95% CI 0.11 to 0.26) in the control group (three RCTs with a total of 104 participants). Based on these three RCTs, the hrHPV clearance was significantly higher in the vaccinated group (250 participants) compared with the control group (RR 2.03; 95% CI 1.30 to 3.16). Similar results were found regarding HPV 16/18 clearance. No significant unsolicited adverse events have been consistently reported.ConclusionsThe efficacy of the therapeutic vaccines in the treatment of CIN 2/3 was modest. Implementation issues such as feasibility, acceptability, adoption and cost-effectiveness need to be further studied.Prospero registration numberCRD42022307418.

Dataset Information

HPV-16 E2 gene disruption and sequence variation in CIN 3 lesions and invasive squamous cell carcinomas of the cervix: relation to numerical chromosome abnormalities.

Aim

Methods

Results

Conclusions

Publications

HPV-16 E2 gene disruption and sequence variation in CIN 3 lesions and invasive squamous cell carcinomas of the cervix: relation to numerical chromosome abnormalities.

Similar Datasets

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