Direct Detection of Cervical Carcinogenesis through mRNA

Skomedal, Hanne; Kraus, Irene; Silva, I.; Molden, Tor; Hovland, Siri; Morland, G.; Morland, E.; Karlsen, Frank

doi:10.1159/000092740

Cited by 4 publications

(3 citation statements)

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“…Although the L1 region does play a role in the replication of the virus, it is not involved in the oncogenic mechanism [ 58 ]. In case of a loss of L1 region, due to viral integration into the human genome, DNA test will incorrectly define the sample as being negative, even though there could be aggressive activity of the virus, which could lead to cellular changes by E6/E7 oncoproteins [ 59 ]. It has been estimated that up to 5% of cancers and CIN3 may not be detectable because of deletions of the HPV L1 region [ 59 , 60 ].…”

Section: Discussionmentioning

confidence: 99%

Analytic and Diagnostic Performances of Human Papillomavirus E6/E7 mRNA Test on up-to 11-Year-Old Liquid-Based Cervical Samples. A Biobank-Based Longitudinal Study

Zappacosta

Sablone

Pansa

et al. 2017

IJMS

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Human Papillomavirus (HPV) E6/E7 mRNA test demonstrated high specificity in detecting HPV infections, but studies assessing its efficacy in terms of cancer risk stratification are lacking. Follow-up studies are arduous and expensive. Biobank would be the answer to the problem, although data investigating the effects of long-term storage on RNA preservation are still needed. We addressed these issues by retrieving 202 residual liquid-based cervical specimens, collected from 149 women attending cervical cancer screening during the years 2001–2012. Samples were stored in Adriatic Biobank at room temperature and without any handing. After calculation of RNA yield and purity, E6/E7 mRNA test was retrospectively performed on each samples, to assess analytic and diagnostic performances. Using automated extraction procedures, RNA of good quantity and quality was obtained. The mean value of RNA concentration was 27.5 ng/μL. The mean A260/A280 ratio was 2.1. An invalid mRNA test result was found in 11.9% of the specimens. Neither RNA integrity, nor analytic performances of mRNA test were influenced by the year of sample collection. In total, 62.4% of the specimens tested as mRNA positive; among these, 89.2% were CIN2+. E6/E7 mRNA was detected in all Squamous Cervical Cancer (SCC) cases. Percentage of positive samples increased with the severity of histological diagnosis. mRNA testing, showing specificity and predictive values of 75.6% and 84.4%, respectively, significantly improved the corresponding values for DNA testing. Thus, the reflex mRNA test was demonstrated to be suitable to triage women with persistent cervical lesions. A “one sample for all” approach is possible, with practical benefits for Biobank-based long-term longitudinal studies, diseases prevention, prediction, diagnosis and treatment.

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Section: Discussionmentioning

confidence: 99%

Analytic and Diagnostic Performances of Human Papillomavirus E6/E7 mRNA Test on up-to 11-Year-Old Liquid-Based Cervical Samples. A Biobank-Based Longitudinal Study

Zappacosta

Sablone

Pansa

et al. 2017

IJMS

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“…This finding underlines a substantial problems linked to DNA techniques. Consensus primer MY091ll PCR target the structural L1 region of the virus; this region is deleted when HPV-DNA is integrated into the host cell genome (26)(27). HC2 technology utilizes long single-stranded RNA probe (about 8000 base pairs) which is complementary to the entire HPV-DNA sequence.…”

Section: Discussionmentioning

confidence: 99%

Is HPV-DNA Testing a Useful Tool in Predicting Low-Grade Squamous Intraepithelial Lesion Outcome? A Retrospective Longitudinal Study

Zappacosta

Caraceni²,

Ciccocioppo³

et al. 2010

Int J Immunopathol Pharmacol

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HPV-DNA testing has entered in clinical practice. Three important questions remain controversial: 1) which is the best HPV-DNA technology? 2) Which age group should be targeted? 3) Is HPV-DNA testing predictive of disease outcome? The answers to these queries represent the endpoints of this study. The population of this retrospective study consisted of 272 women, each one having: baseline cytological diagnosis of Low-grade Squamous Intraepithelial Lesion (LSIL); baseline HPV-DNA reports by Hybrid Capture 2 (HC2) and MY09/11 consensus primers PCR; follow-up duration over 3-years; cytological report of disease status at follow-up time. Firstly, we assessed the concordance and the performances of both HPV-DNA testing, then we correlated respectively HPV-DNA results and age of patients to disease outcome. DNA testing methods agreed in 83.4% of cases (K=0.66). Baseline HPV-DNA result was not significantly associated to disease outcome (p=0.06). Within HPV-DNA positive group, we found no evidence of correlation between age and LSIL prognosis (p=0.89). Confining the analysis to age-stratified HPV-DNA negative women, the differences were statistically significant (p=0.01). In conclusion, HPV-DNA testing gives no information about the real behaviour of cervical abnormalities. These findings suggest the demand for additive markers, reflecting the risk of progression, in prevention strategy and clinical approach.

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“…At present, only the above listed five oncogenic HPV types are detectable by Nuclisens technology; at the first sight this may be considered a disadvantage in comparison with the available DNA genotyping strategies. However, studies carried out to find E6/E7 mRNA in cervical smears of women with cervical cancer, demonstrated a 100% coverage by these genotypes Skomedal et al, 2006).…”

Section: # ! 61mentioning

confidence: 99%

Overview on Molecular Markers to Implement Cervical Cancer Prevention: Challenges and Perspectives

Rosini¹,

Zappacosta²

2012

Human Papillomavirus and Related Diseases - From Bench to Bedside - Research Aspects

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Direct Detection of Cervical Carcinogenesis through mRNA

Cited by 4 publications

References 0 publications

Analytic and Diagnostic Performances of Human Papillomavirus E6/E7 mRNA Test on up-to 11-Year-Old Liquid-Based Cervical Samples. A Biobank-Based Longitudinal Study

Analytic and Diagnostic Performances of Human Papillomavirus E6/E7 mRNA Test on up-to 11-Year-Old Liquid-Based Cervical Samples. A Biobank-Based Longitudinal Study

Is HPV-DNA Testing a Useful Tool in Predicting Low-Grade Squamous Intraepithelial Lesion Outcome? A Retrospective Longitudinal Study

Overview on Molecular Markers to Implement Cervical Cancer Prevention: Challenges and Perspectives

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