title: The relationship between cytokines and HPV-16, HPV-16 E6, E7, and high-risk HPV viral load in the uterine cervix.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Seung-Hun
authors.initials: SH
authors.lastname: Song
authors.forename: Jae-Kwan
authors.initials: JK
authors.lastname: Lee
authors.forename: Oye-Sun
authors.initials: OS
authors.lastname: Seok
authors.forename: Ho-Suk
authors.initials: HS
authors.lastname: Saw
mesh_terms: 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
chemical_list: 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