title: HPV-negative carcinoma of the uterine cervix: a distinct type of cervical cancer with poor prognosis.
abstract: OBJECTIVE
  Using highly sensitive polymerase chain reaction (PCR) techniques, we reanalysed all cervical carcinomas (CCs) found to be human papillomavirus (HPV)-negative by Hybrid Capture 2 (HC2) to determine the prevalence of true HPV-negativity. We also evaluated the characteristics of the patients with tumours with confirmed HPV-negativity.
  
  
  METHODS
  Observational study.
  
  
  METHODS
  Barcelona, Spain.
  
  
  METHODS
  A cohort of 136 women with CC (32 adenocarcinomas, 104 squamous cell carcinomas) who had pre-treatment HC2 testing.
  
  
  METHODS
  All negative cases were reanalysed and genotyped for HPV using three PCR assays (SPF10, GP5+/6+ and E7-specific assay).
  
  
  METHODS
  Percentage of confirmed HPV-negative and HPV-positive tumours. Clinicopathological features and disease-free survival (DFS) and overall survival (OS) of both groups.
  
  
  RESULTS
  Fourteen of 136 women (10.2%) were negative for HPV by HC2. After reanalysis by PCR-based techniques only 8/136 (5.8%) tumours were confirmed as HPV-negative, whereas in six cases different HPVs were identified [HPV-11, -16 (two tumours), -18, -45, and -68]. Confirmed HPV-negativity was more frequent in adenocarcinomas than in squamous cell carcinomas (5/32, 15.6% versus 3/104, 2.9%, respectively; P = 0.017). Patients with CCs with confirmed HPV-negativity had significantly worse DFS than women with HPV-positive tumours [51.9 months (95% CI 12.2-91.7 months) versus 109.9 months (95% CI 98.2-121.5 months); P = 0.010]. In the multivariate analysis HPV-negativity and International Federation of Gynecology and Obstetrics (FIGO) staging were associated with increased risk of progression and mortality.
  
  
  CONCLUSIONS
  An HC2-negative result is an uncommon finding in women with CC, but in almost half of these cases HPVs are identified by more sensitive techniques. CCs with confirmed HPV-negativity are more frequently adenocarcinomas, and seem to be associated with worse DFS.
authors.affiliation: Department of Pathology, Centre de Recerca en Salut Internacional de Barcelona (CRESIB), Hospital Clínic, University of Barcelona, Faculty of Medicine, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Rodríguez-Carunchio
authors.forename: I
authors.initials: I
authors.lastname: Soveral
authors.forename: R D M
authors.initials: RD
authors.lastname: Steenbergen
authors.forename: A
authors.initials: A
authors.lastname: Torné
authors.forename: S
authors.initials: S
authors.lastname: Martinez
authors.forename: P
authors.initials: P
authors.lastname: Fusté
authors.forename: J
authors.initials: J
authors.lastname: Pahisa
authors.forename: L
authors.initials: L
authors.lastname: Marimon
authors.forename: J
authors.initials: J
authors.lastname: Ordi
authors.forename: M
authors.initials: M
authors.lastname: del Pino
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000821:virology; D002288:Adenocarcinoma, Mucinous / Q000473:pathology* / Q000821:virology; D000328:Adult; D000368:Aged; D018196:Carcinoma, Adenosquamous / Q000473:pathology* / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000821:virology; D015331:Cohort Studies; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000821:virology
chemical_list: D004279:DNA, Viral
keywords: Cervical cancer; human papillomavirus; p16; p53; prognosis; uterine cervix