title: Prognostic impact of human papilloma virus (HPV) genotyping and HPV-16 subtyping in vaginal carcinoma.
abstract: OBJECTIVE
  The objectives of this study are to investigate the human papilloma virus (HPV) distribution in vaginal cancer and to evaluate HPV-genotype as well as HPV16-variant impact on prognosis.
  
  
  METHODS
  Sixty-nine patients diagnosed with primary vaginal carcinoma (1975-2002) were included in the study. Detection of twelve high-risk HPV (hr HPV) and two low-risk HPV (lr HPV) was performed with realtime-PCR. Samples positive for HPV-16 were analyzed for variants in the E6-gene with PCR and pyrosequencing.
  
  
  RESULTS
  53.6% (37/69) of the tumors were found to be HPV-positive, mostly for HPV-16 (N=26). Other HPV-types were HPV-18 (N=2), HPV-31 (N=2), HPV-33 (N=2), HPV-45 (N=1), HPV-52 (N=2), HPV-56 (N=1) and HPV-58 (N=1). Only European subtypes of HPV-16 were represented and the two most common HPV-16-variants were E-p (N=13) and E-G350 (N=11). Patients with HPV-positive tumors (N=37) had a significantly (log-rank test=3.341; p=0.0008) superior 5-year overall survival rate as well as cancer-specific survival rate and progression-free survival rate (p=0.0002; p=0.0004), compared with patients with HPV-negative tumors (N=32). Interestingly, patients with HPV-16-positive tumors had a superior overall survival compared with patients with tumors containing other HPV-genotypes. In a Cox proportional multivariate analysis age, tumor size, and HPV-status were independent and significant prognostic factors with regard to overall survival rate.
  
  
  CONCLUSIONS
  HPV-status is of prognostic importance in vaginal carcinoma and varies with viral genotype. In this era of HPV-vaccination, genotypes other than those included in the vaccination program could still lead to vaginal carcinoma with unfavorable prognosis.
authors: Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden. gabriella.lillsunde-larsson@orebroll.se
authors: Gabriella Lillsunde
authors: GL
authors: Larsson
authors: Gisela
authors: G
authors: Helenius
authors: Sören
authors: S
authors: Andersson
authors: Bengt
authors: B
authors: Sorbe
authors: Mats G
authors: MG
authors: Karlsson
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000532:radiotherapy / Q000821:virology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052685:Alphapapillomavirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D001918:Brachytherapy; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000532:radiotherapy / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis / Q000302:isolation & purification; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D005838:Genotype; D060005:Genotyping Techniques; D061809:Human Papillomavirus DNA Tests; D052162:Human papillomavirus 16 / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009856:Oncogene Proteins, Viral / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics; D016019:Survival Analysis; D013548:Sweden; D014625:Vaginal Neoplasms / Q000401:mortality / Q000532:radiotherapy / Q000821:virology*
chemical_list: D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D005819:Genetic Markers; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins