The relationship between cytokines and HPV-16, HPV-16 E6, E7, and high-risk HPV viral load in the uterine cervix.
OBJECTIVE
To investigate intralesional cytokine levels in precancerous lesions of the uterine cervix and their relationship with human papillomavirus (HPV) type 16, HPV type 16 E6/E7, and high-risk HPV viral load.


METHODS
We performed a prospective study of 67 patients between May 2005 and December 2005. Hybrid Capture II testing was used to identify patients as high-risk HPV DNA-positive or -negative. HPV DNA Chip test was performed for HPV genotyping in all cases found to be HPV DNA-positive. Real-time PCR was used to quantify HPV-16 E6, E7, interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma) transcripts.


RESULTS
Among high-risk HPV-infected women, intralesional TNF-alpha, IL-6, IL-10, and IFN-gamma levels had no significant differences according to histologic grade. In multivariate logistic regression analysis, TNF-alpha, IL-6, IL-10, and IFN-gamma were not associated with HPV-16. Increased IFN-gamma was significantly associated with HPV-16 E6- and E7-positive (OR 28.197, 95% CI: 2.658-299.110; OR 19.617, 95% CI: 2.135-180.253, respectively), whereas TNF-alpha, IL-6, and IL-10 were not associated with HPV-16 E6 and E7. In multiple regression analysis, elevated IFN-gamma was significantly associated with increased HPV viral load (P=0.039), whereas TNF-alpha, IL-6, and IL-10 were not significantly associated with HPV viral load.


CONCLUSIONS
Among HPV-infected women, IFN-gamma is significantly associated with HPV-16 E6, E7, and high-risk HPV viral load in the uterine cervix. Thus, increased intralesional IFN-gamma may be considered to be a prognostic marker for oncogenic potential of high-risk HPV.
Song
Seung-Hun
SH
Department of Obstetrics and Gynecology, School of Medicine, Korea University, Seoul, Republic of Korea.
Lee
Jae-Kwan
JK
Seok
Oye-Sun
OS
Saw
Ho-Suk
HS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000276:immunology*; D005260:Female; D005838:Genotype; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis* / Q000235:genetics; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000821:virology*; D019562:Viral Load
D016207:Cytokines; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16