title: Poor prognosis associated with human papillomavirus α7 genotypes in cervical carcinoma cannot be explained by intrinsic radiosensitivity.
abstract: OBJECTIVE
  To investigate the relationship between human papillomavirus (HPV) genotype and outcome after radiation therapy and intrinsic radiosensitivity.
  
  
  METHODS
  HPV genotyping was performed on cervix biopsies by polymerase chain reaction using SPF-10 broad-spectrum primers, followed by deoxyribonucleic acid enzyme immunoassay and genotyping by reverse hybridization line probe assay (LiPA25) (version 1) (n=202). PapilloCheck and quantitative reverse transcription-polymerase chain reaction were used to genotype cervix cancer cell lines (n=16). Local progression-free survival after radiation therapy alone was assessed using log-rank and Cox proportionate hazard analyses. Intrinsic radiosensitivity was measured as surviving fraction at 2 Gy (SF2) using clonogenic assays.
  
  
  RESULTS
  Of the 202 tumors, 107 (53.0%) were positive for HPV16, 29 (14.4%) for HPV18, 9 (4.5%) for HPV45, 23 (11.4%) for other HPV genotypes, and 22 (10.9%) were negative; 11 (5.5%) contained multiple genotypes, and 1 tumor was HPV X (0.5%). In 148 patients with outcome data, those with HPVα9-positive tumors had better local progression-free survival compared with α7 patients in univariate (P<.004) and multivariate (hazard ratio 1.54, 95% confidence interval 1.11-1.76, P=.021) analyses. There was no difference in the median SF2 of α9 and α7 cervical tumors (n=63). In the cell lines, 9 were α7 and 4 α9 positive and 3 negative. There was no difference in SF2 between α9 and α7 cell lines (n=14).
  
  
  CONCLUSIONS
  The reduced radioresponsiveness of α7 cervical tumors is not related to intrinsic radiosensitivity.
authors: Translational Radiobiology Group, Institute of Cancer Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom.
authors: John S
authors: JS
authors: Hall
authors: Rohan
authors: R
authors: Iype
authors: Lucile S C
authors: LS
authors: Armenoult
authors: Janet
authors: J
authors: Taylor
authors: Crispin J
authors: CJ
authors: Miller
authors: Susan
authors: S
authors: Davidson
authors: Silvia
authors: S
authors: de Sanjose
authors: Xavier
authors: X
authors: Bosch
authors: Peter L
authors: PL
authors: Stern
authors: Catharine M L
authors: CM
authors: West
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052685:Alphapapillomavirus / Q000235:genetics* / Q000528:radiation effects; D001706:Biopsy; D045744:Cell Line, Tumor; D002584:Cervix Uteri / Q000473:pathology / Q000821:virology; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000821:virology*; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D011836:Radiation Tolerance; D012189:Retrospective Studies; D013045:Species Specificity; D013997:Time Factors; D014021:Tissue Preservation; D002583:Uterine Cervical Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000821:virology*; D055815:Young Adult
chemical_list: D017931:DNA Primers