To examine the specificity of human papillomavirus (HPV) E6/E7 mRNA testing for intraepithelial precursor lesions and invasive carcinoma of the uterine cervix in 358 women and compare the results with those of the most widely used DNA technique.
For HPV E6/E7 mRNA testing an amplification assay was used. For DNA determination a hybridization assay was applied. Both techniques were used simultaneously in patients with normal morphology (150), cervical intraepithelial neoplasia (173) and invasive carcinoma of the cervix (35).
HPV DNA positivity rates were significantly higher than E6/E7 mRNA in women with normal morphology (21-7%), cervical intraepithelial neoplasia (CIN) 1 and 2 (75-43%), and CIN 3 (93-63%). In invasive cervical carcinoma, both methods tested equally high (94% vs. 97%). Considering that E6/E7 up-regulation represents the initial step in cervical carcinogenesis, it can be assumed that this test allows a more specific detection of lesions with a potential for progression.
HPV E6/E7 mRNA may serve as a more specific discriminator between transient cervical dysplasias and potentially progressive lesions. Accordingly, testing for high-risk HPV E6/E7 mRNA might reduce the psychologic burden associated with HPV-DNA testing.
[Show abstract][Hide abstract] ABSTRACT: NOWADAYS, THERE ARE MOLECULAR BIOLOGY TECHNIQUES PROVIDING INFORMATION RELATED TO CERVICAL CANCER AND ITS CAUSE: the human Papillomavirus (HPV), including DNA microarrays identifying HPV subtypes, mRNA techniques such as nucleic acid based amplification or flow cytometry identifying E6/E7 oncogenes, and immunocytochemistry techniques such as overexpression of p16. Each one of these techniques has its own performance, limitations and advantages, thus a combinatorial approach via computational intelligence methods could exploit the benefits of each method and produce more accurate results. In this article we propose a clinical decision support system (CDSS), composed by artificial neural networks, intelligently combining the results of classic and ancillary techniques for diagnostic accuracy improvement. We evaluated this method on 740 cases with complete series of cytological assessment, molecular tests, and colposcopy examination. The CDSS demonstrated high sensitivity (89.4%), high specificity (97.1%), high positive predictive value (89.4%), and high negative predictive value (97.1%), for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In comparison to the tests involved in this study and their combinations, the CDSS produced the most balanced results in terms of sensitivity, specificity, PPV, and NPV. The proposed system may reduce the referral rate for colposcopy and guide personalised management and therapeutic interventions.
[Show abstract][Hide abstract] ABSTRACT: Behaviourally HIV-infected adolescent females are at higher risk for abnormal cervical cytology and HPV infection compared to those who are uninfected, but data on perinatally HIV-infected adolescent females are lacking.
Cervical cytology, HPV infection and E6/E7 mRNA were assessed in sexually active 12-24-year-old adolescent females: perinatally HIV-infected (group 1, n = 40), behaviourally HIV-infected (group 2, n = 10), and HIV-uninfected (group 3, n = 10).
Median age was lower in group 1 (18 years) than in groups 2 (24 years) and 3 (20.5 years) (P < 0.001), and median time since sexual debut was shorter: 2 vs 5 vs 4 years (P < 0.001). More trial participants in group 1 than group 2 were on antiretrovirals (90% vs 70%; P <0.001). Abnormal cervical cytology (atypical squamous cells of undetermined significance and higher) was observed in 30% (group 1), 40% (group 2) and 30% (group 3) (P = 0.92), whereas high-risk HPV infection was observed in 45%, 45% and 40%, respectively (P = 1.00). Positive E6/E7 mRNA was found in 28% of group 1, but not in other groups. High-risk HPV infection predicted abnormal cytology in all groups [OR 6.77, 95% confidence interval (CI) 1.99-23.0; P = 0.001). Additionally, plasma HIV RNA ≥50 copies/mL (OR 13.3, 95% CI 1.16-153.06; P = 0.04) predicted abnormal cytology in HIV-infected adolescent females.
Despite the younger age and shorter time since sexual debut, cervical cytological abnormalities and HPV infection were as common in perinatally HIV-infected as in behaviourally infected and uninfected adolescents. HPV vaccination, pre-cancer screening and antiretroviral treatment in HIV-infected female adolescents should be implemented to minimise the risk of cervical cancer.
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