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Increased levels of HPV16 E6*I transcripts in high‐grade cervical cytology and histology (CIN II+) detected by rapid real‐time RT‐PCR amplification
Author(s) -
Kösel S.,
Burggraf S.,
Engelhardt W.,
Olgemöller B.
Publication year - 2007
Publication title -
cytopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.512
H-Index - 48
eISSN - 1365-2303
pISSN - 0956-5507
DOI - 10.1111/j.1365-2303.2007.00481.x
Subject(s) - cervical intraepithelial neoplasia , dysplasia , medicine , cytology , histology , gastroenterology , colposcopy , cervical cancer , pathology , cancer
Objective: As cervical dysplasia may regress to normal cytology or progress to cervical carcinoma, it would be valuable to have a diagnostic tool to help decide whether therapeutic conization should be performed. Methods: Cervical samples of 301 HPV16 positive women were collected in RNA later reagent to prevent RNA degradation. Relative levels of HPV16 DNA and HPV16 E6*I mRNA in the samples were determined using real‐time polymerase chain reaction. Findings were correlated with histological diagnoses and cytological follow‐up. Results: HPV16 E6*I mRNA levels were significantly higher in women with cytologically diagnosed severe cervical dysplasia (mean normalized ratio = 0.25) than in those with mild‐to‐moderate dysplasia (mean norm. ratio = 0.12), atypical squamous cells of uncertain origin (mean norm. ratio = 0.071) or normal cytology (mean norm. ratio = 0.034). Viral DNA levels were not significantly different between severe and mild‐to‐moderate dysplasia (mean norm. ratios, 55.8 and 63.5, respectively). The PPV for a histological diagnosis of severe cervical dysplasia [cervical intraepithelial neoplasia (CIN) II+] increased with the amounts of E6*I mRNA to more than 90% whereas the sensitivity decreased. The absence of HPV16 E6*I transcripts as well as HPV16 DNA considerably increased the negative predictive value and the specificity. However, low concentrations (or complete absence) of E6*I mRNA did not preclude a CIN II+ diagnosis. Conclusions: Although the sensitivity is low, high levels of HPV16 E6*I mRNA are indicative of CIN II+ in cytologically diagnosed cervical dysplasia of individual patients. Thus, quantification of HPV16 E6*I mRNA could be helpful in managing follow‐up and treatment in a subset of HPV16 positive women.