Tamina Kienka1, Matthew G Varga2,3, Josie Caves2, Jennifer S Smith2,3, Vijay Sivaraman1. 1. Department of Biological and Biomedical Sciences, North Carolina Central University, Durham, North Carolina. 2. Department of Epidemiology, UNC Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina. 3. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
Abstract
STATEMENT OF THE PROBLEM: Human papillomavirus (HPV) infection is known to contribute to cervical carcinogenesis, yet other cofactors that may contribute to oncogenesis are poorly understood. Herein, we examine whether the Epstein-Barr virus (EBV) and human cytomegalovirus (CMV), two oncomodulatory viruses, are associated with HPV-mediated cervical neoplastic progression. METHODS: Sixty patient cervical brush samples from a study of North Carolina women were obtained. HPV RNA positivity was determined by Aptima testing (Hologic Corporation, Marlborough, MA). The level of viral transcripts for EBV and CMV was quantified (reverse transcription polymerase chain reaction analysis), and the coinfection status with HPV was then compared with the patient's cervical cytology grade. RESULTS: Over one-third (38.3%) of the study population was CMV positive, whereas 43.3% was EBV positive. When sample data were stratified by the cytology grade, 36.5% (19/52) of normal patients, 75% (3/4) of low-grade squamous intraepithelial lesions (LSIL), and 100% (4/4) of patients with high-grade SIL (HSIL) were EBV positive. Conversely, 35.2% (18/52) of normal patients, 25% (1/4) of patients with LSIL, and 50% (2/4) of patients with HSIL were CMV positive. When examining only HPV positive-associated HSIL, 100% (4/4) were positive for both HPV and EBV detection. This suggests that co-viral detection with HPV and EBV is associated with more advanced HSIL cervical lesions, while CMV displayed no clear association with a higher grade of cervical cytology. CONCLUSIONS: Co-viral detection with EBV may increase the oncogenicity and/or serve as a viral marker of progression to HPV-associated high-grade cervical dysplasia.
STATEMENT OF THE PROBLEM: Humanpapillomavirus (HPV) infection is known to contribute to cervical carcinogenesis, yet other cofactors that may contribute to oncogenesis are poorly understood. Herein, we examine whether the Epstein-Barr virus (EBV) and human cytomegalovirus (CMV), two oncomodulatory viruses, are associated with HPV-mediated cervical neoplastic progression. METHODS: Sixty patient cervical brush samples from a study of North Carolina women were obtained. HPV RNA positivity was determined by Aptima testing (Hologic Corporation, Marlborough, MA). The level of viral transcripts for EBV and CMV was quantified (reverse transcription polymerase chain reaction analysis), and the coinfection status with HPV was then compared with the patient's cervical cytology grade. RESULTS: Over one-third (38.3%) of the study population was CMV positive, whereas 43.3% was EBV positive. When sample data were stratified by the cytology grade, 36.5% (19/52) of normal patients, 75% (3/4) of low-grade squamous intraepithelial lesions (LSIL), and 100% (4/4) of patients with high-grade SIL (HSIL) were EBV positive. Conversely, 35.2% (18/52) of normal patients, 25% (1/4) of patients with LSIL, and 50% (2/4) of patients with HSIL were CMV positive. When examining only HPV positive-associated HSIL, 100% (4/4) were positive for both HPV and EBV detection. This suggests that co-viral detection with HPV and EBV is associated with more advanced HSIL cervical lesions, while CMV displayed no clear association with a higher grade of cervical cytology. CONCLUSIONS: Co-viral detection with EBV may increase the oncogenicity and/or serve as a viral marker of progression to HPV-associated high-grade cervical dysplasia.