title: Integrated human papillomavirus types 52 and 58 are infrequently found in cervical cancer, and high viral loads predict risk of cervical cancer.
abstract: OBJECTIVE
  The aim of this prospective study was to analyze whether integration or high viral loads of human papillomavirus (HPV) is essential for malignant transformation of HPV types 52 and 58 as well as types 16 and 18.
  
  
  METHODS
  Cervical swabs from 178 consecutive patients, including 81 with invasive cervical cancers and 97 with cervical intraepithelial neoplasias (CIN) II-III, were collected and examined to determine the physical status and viral load of HPV types 16, 18, 52 and 58 DNA using genechip and real-time PCR (polymerase chain reaction) analysis.
  
  
  RESULTS
  In cervical cancer patients, the integrated form of HPV 52 and 58 DNA was found in 25.0% and 12.5% of swabs, respectively; while HPV16 and 18 DNA was found in 82.6% and 100% of swabs, respectively (P < 0.01, for pair-wise comparison of types 16, 18 versus types 52, 58). The viral loads reflected by the amount of E6 for HPV 16, 18, or 52 were significantly increased in invasive cervical cancer compared to CINII-III (P = 0.022 for type 16, P = 0.003 for type18, and P = 0.001 for type 52, respectively). Area under the receiver operating characteristic (ROC) curve for cervical cancer versus CIN II-III was 73.8%, 92.9%, and 88.5% for HPV 16, 18, and 52, respectively, indicating that real-time PCR had good diagnostic value in differentiating cervical cancer from CIN II-III.
  
  
  CONCLUSIONS
  Infrequent integration of HPV 52 and 58 DNA in cervical cancer suggests that it is not prerequisite for progression to cervical cancer. High viral loads (E6) of HPV 16, 18, and 52 DNA may be predictive of the transition of CIN II-III to cervical cancer. Our results indicate that both viral DNA physical status and viral loads of HPV are important factors in the carcinogenesis of different HPV types.
authors.affiliation: Gynecologic Cancer Center, Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan, ROC.
authors.forename: Chih-Ming
authors.initials: CM
authors.lastname: Ho
authors.forename: Tsai-Yen
authors.initials: TY
authors.lastname: Chien
authors.forename: Shih-Hung
authors.initials: SH
authors.lastname: Huang
authors.forename: Bor-Heng
authors.initials: BH
authors.lastname: Lee
authors.forename: Shwu-Fen
authors.initials: SF
authors.lastname: Chang
mesh_terms: D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics / Q000502:physiology*; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D011446:Prospective Studies; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology*; D019562:Viral Load; D016662:Virus Integration; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000473:pathology / Q000821:virology*
chemical_list: D004279:DNA, Viral; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins