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Correlation of Human Papillomavirus Type 16 and Human Papillomavirus Type 18 E7 Messenger RNA Levels with Degree of Cervical Dysplasia

Departments of ¹ Epidemiology and ² Gynecologic Oncology, and ³ Biomedical Engineering Center, The University of Texas M.D. Anderson Cancer Center; ⁴ Division of Occupational and Environmental Health, The University of Texas School of Public Health; ⁵ Department of Diagnostic Sciences, The University of Texas Dental Branch, Houston, Texas; ⁶ Department of Cancer Imaging, British Columbia Cancer Research Centre, The British Columbia Cancer Agency, Vancouver, British Columbia, Canada; and ⁷ Department of Hematology and Oncology, Emory University Winship Cancer Institute, Atlanta, Georgia

Requests for reprints: Karen Adler-Storthz, Department of Diagnostic Sciences, University of Texas Dental Branch, 6516 M.D. Anderson Boulevard, DBB, 4.133, Houston, TX 77030. E-mail: karen.a.storthz{at}uth.tmc.edu

Infection with certain types of human papillomavirus (HPV) is a necessary event in the development of cervical carcinoma; however, not all women who become infected with HPV will progress to cancer. Much is known about the molecular influence of HPV E6 and E7 proteins on the malignant transformation. Little is known about the additional factors needed to drive the process. Quantitative real-time PCR was used to quantitate mRNA expression of the E7 gene in women exhibiting normal epithelium, low-grade squamous intraepithelial lesions (LSIL), and high-grade squamous intraepithelial lesions (HSIL). Prevalence of mRNA transcripts was lower among normal women (27%) than for women with LSIL (40%) and HSIL (37%). Mean levels ranged from 2.0 (ln scale per 20 ng cDNA) among normal women to 4.2 among those with HSIL, with a significant trend (P = 0.008). This trend was only significant for HPV 18 transcripts if separately analyzed by HPV type. The transcriptional activity of HPV 18 is higher than that of HPV 16 and increases with increasing level of dysplasia. This is in concert with the findings of other studies, and reinforces the notion that HPV 18 is a more aggressive viral type. Real-time PCR of viral transcripts could provide a more efficient method to analyze the oncogenic potential within cells from a cervical swab, thus providing a way to better screen women who may progress to higher grade lesions or invasive carcinoma from those who will spontaneously regress.

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