OBJECTIVES: We have previously demonstrated that Brn-3a cellular transcription factor activates transcription of the human papillomavirus (HPV) E6 and E7 oncogenes in human cervical cancer cells and that Brn-3a levels are dramatically elevated in biopsies from women with high-grade cervical neoplasia. The aim of this study was to establish the relationship between Brn-3a levels in Pap smears and the histological diagnoses. We also analysed whether Brn-3a levels can be used in combination with Pap smear to predict the presence of cervical intraepithelial lesion. METHODS: Two hundred thirty-eight women who were referred with abnormal Pap smear underwent a diagnostic colposcopy, repeat in-study Pap smear, colposcopically directed biopsy, and assessment of Brn-3a and HPV-16 E6 m-RNA levels. Data were analysed to assess the association between Brn-3a levels and the histological diagnosis. RESULTS: Brn-3a was readily measured in smears and showed a statistically significant correlation with the grade of cervical abnormality. Positive Brn-3a is associated with increased relative risk of higher-grade lesion. Moreover, measurement of Brn-3a levels in smears can be used to detect a significant proportion of cervical lesions that were missed by Pap smear. CONCLUSION: Measurement of Brn-3a levels in routinely taken Pap smears is a feasible technique that correlates with the severity of the epithelial abnormality and is a useful adjunct to cytology. Brn-3a appears to have great promise since it detects activation of oncogenic HPVs rather than simply detecting their presence, as is currently being done.
OBJECTIVES: We have previously demonstrated that Brn-3a cellular transcription factor activates transcription of the human papillomavirus (HPV) E6 and E7 oncogenes in human cervical cancer cells and that Brn-3a levels are dramatically elevated in biopsies from women with high-grade cervical neoplasia. The aim of this study was to establish the relationship between Brn-3a levels in Pap smears and the histological diagnoses. We also analysed whether Brn-3a levels can be used in combination with Pap smear to predict the presence of cervical intraepithelial lesion. METHODS: Two hundred thirty-eight women who were referred with abnormal Pap smear underwent a diagnostic colposcopy, repeat in-study Pap smear, colposcopically directed biopsy, and assessment of Brn-3a and HPV-16 E6 m-RNA levels. Data were analysed to assess the association between Brn-3a levels and the histological diagnosis. RESULTS:Brn-3a was readily measured in smears and showed a statistically significant correlation with the grade of cervical abnormality. Positive Brn-3a is associated with increased relative risk of higher-grade lesion. Moreover, measurement of Brn-3a levels in smears can be used to detect a significant proportion of cervical lesions that were missed by Pap smear. CONCLUSION: Measurement of Brn-3a levels in routinely taken Pap smears is a feasible technique that correlates with the severity of the epithelial abnormality and is a useful adjunct to cytology. Brn-3a appears to have great promise since it detects activation of oncogenic HPVs rather than simply detecting their presence, as is currently being done.
Authors: Emmanouil Papasavvas; Andrew V Kossenkov; Livio Azzoni; Nicola M Zetola; Agnieszka Mackiewicz; Brian N Ross; Matthew Fair; Surya Vadrevu; Doreen Ramogola-Masire; Ian Sanne; Cynthia Firnhaber; Luis J Montaner Journal: Carcinogenesis Date: 2019-04-29 Impact factor: 4.944