title: Does human papillomavirus infection imply a different prognosis in vulvar squamous cell carcinoma?
abstract: BACKGROUND
  Two independent pathways in the development of vulvar squamous cell carcinoma (VSCC) have been described, one related to and the other independent of high-risk human papillomavirus (HR-HPV). The aim of our study was to evaluate whether the HPV status has a prognostic significance or can predict response to radiotherapy.
  
  
  METHODS
  All VSCC diagnosed from 1995 to 2009 were retrospectively evaluated (n=98). HPV infection was detected by amplification of HPV DNA by PCR using SPF-10 primers and typed by the INNO-LIPA HPV research assay. p16(INK4a) expression was determined by immunohistochemistry. Disease-free and overall survival (DFS and OS) were estimated by Kaplan-Meier analysis with the log-rank test and a multivariate Cox proportional hazard's model.
  
  
  RESULTS
  HR-HPV DNA was detected in 19.4% of patients. HPV16 was the most prevalent genotype (73.7% of cases). p16(INK4a) stained 100% HPV-positive and 1.3% HPV-negative tumors (p<.001). No differences were found between HPV-positive and -negative tumors in terms of either DFS (39.8% vs. 49.8% at 5 years; p=.831), or OS (67.2% vs. 71.4% at 5 years; p=.791). No differences in survival were observed between HPV-positive and -negative patients requiring radiotherapy (hazard ratio [HR] 1.04, 95% confidence interval [CI] .45 to 2.41). FIGO stages III-IV (p=.002), lymph node metastasis (p=.030), size ≥ 20 mm (p=.023), invasion depth (p=.020) and ulceration (p=.032) were associated with increased mortality but in multivariated only lymph node metastasis retained the association (HR 13.28, 95% CI 1.19 to 148.61).
  
  
  CONCLUSIONS
  HPV-positive and -negative VSCCs have a similar prognosis. Radiotherapy does not increase survival in HPV-positive women.
authors.affiliation: Institut Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Faculty of Medicine-University of Barcelona, Barcelona, Spain.
authors.forename: Immaculada
authors.initials: I
authors.lastname: Alonso
authors.forename: Victoria
authors.initials: V
authors.lastname: Fusté
authors.forename: Marta
authors.initials: M
authors.lastname: del Pino
authors.forename: Paola
authors.initials: P
authors.lastname: Castillo
authors.forename: Aureli
authors.initials: A
authors.lastname: Torné
authors.forename: Pere
authors.initials: P
authors.lastname: Fusté
authors.forename: Jose
authors.initials: J
authors.lastname: Rios
authors.forename: Jaume
authors.initials: J
authors.lastname: Pahisa
authors.forename: Juan
authors.initials: J
authors.lastname: Balasch
authors.forename: Jaume
authors.initials: J
authors.lastname: Ordi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D011836:Radiation Tolerance; D012189:Retrospective Studies; D014846:Vulvar Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy / Q000821:virology*
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D009363:Neoplasm Proteins