title: Infection of human papillomavirus and overexpression of dihydrodiol dehydrogenase in uterine cervical cancer.
abstract: OBJECTIVE
  To determine the association of human papillomavirus (HPV) infection with the expression of dihydrodiol dehydrogenase (DDH) in uterine cervical cancer (UCC).
  
  
  METHODS
  In situ hybridization (ISH) and immunohistochemistry were applied to examine pathological specimens of 145 patients with UCC.
  
  
  RESULTS
  By ISH, HPV16/18 DNA was detected in 108 (74.5%) UCC cases. DDH expression determined by immunohistochemistry was detected in 81 (75%) lesions among 108 HPV-positive cases. In contrast, of 37 HPV-negative cases, DDH was only detected in 16 (43.2%) of the lesions. A significant correlation was found between DDH expression and the presence of HPV (P < 0.001), FIGO stage (P = 0.004), lymph node involvement (P < 0.001), as well as patients' survival (P = 0.002). In vitro, DDH expression was also found closely associated with HPV infection, and DDH content was proportional to cell sensitivity for cisplatin and doxorubicin.
  
  
  CONCLUSIONS
  HPV infection provokes local inflammation, which can then induce DDH expression and drug resistance in UCC. The detailed biological relationship among HPV infection, expression of DDH and drug resistance, however, remains to be clarified.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Ueda
authors.forename: Yao-Ching
authors.initials: YC
authors.lastname: Hung
authors.forename: Jin-Tang
authors.initials: JT
authors.lastname: Chen
authors.forename: Shiow-Her
authors.initials: SH
authors.lastname: Chiou
authors.forename: Hsuan-Hua
authors.initials: HH
authors.lastname: Huang
authors.forename: Tze-Yi
authors.initials: TY
authors.lastname: Lin
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Terai
authors.forename: Kuan-Chih
authors.initials: KC
authors.lastname: Chow
mesh_terms: D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004279:DNA, Viral / Q000032:analysis; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000821:virology; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics*; D052161:Human papillomavirus 18 / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000821:virology; D010088:Oxidoreductases / Q000096:biosynthesis*; D030361:Papillomavirus Infections / Q000150:complications* / Q000201:enzymology* / Q000821:virology; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000821:virology*
chemical_list: D004279:DNA, Viral; D004317:Doxorubicin; D010088:Oxidoreductases; C048338:trans-1,2-dihydrobenzene-1,2-diol dehydrogenase; D002945:Cisplatin