title: Recurrent high-grade cervical lesion after primary conization is associated with persistent human papillomavirus infection in Norway.
abstract: OBJECTIVE
  This retrospective registry-based study aimed to assess the human papillomavirus (HPV)-type distribution in primary and recurrent high-grade cervical intraepithelial neoplasia (CIN2+), and to discriminate pre-existing from newly-acquired infections.
  
  
  METHODS
  Cervical specimens from 58 women (median age (Q1-Q3): 37.6 (31.7-44.9)) who underwent primary (1998-2003) and repeat conizations were confirmed as CIN2+ during expert pathology review. HPV testing was performed using PCR MP-TS123 Luminex for 16 HPV types. Molecular HPV16 E6 and HPV18 LCR DNA sequencing was performed on specimens with persistent HPV16/18.
  
  
  RESULTS
  All 58 paired cones were HPV positive; 49 had CIN3+ in the primary cone. Forty-seven (95.9%) women with primary CIN3+ and recurrent CIN2+ had persistent high-risk (hr) HPV infection, of which 74.5% were HPV16/18. Two women had probable newly-acquired HPV16/52/56 and HPV39 infections. One woman with persistent HPV52 also had a probable new HPV16 E6 variant in the recurrent CIN2+. Median time delay (Q1-Q3) between conizations was 2.0 years (1.1-4.0), being shorter for women older than 40 years: 2.6 years (1.1-3.7) than for women younger than 40 years: 6.0 years (2.0-8.7). Primary conization histology revealed CIN3, cervical adenocarcinoma in situ and microinvasive carcinomas in 43 (87.8%), 5 (10.2%) and 1 (2.0%) women, respectively. Primary HPV16- and HPV18-infected CIN3+ had a shorter delay between conizations: 1.8years (1.2-4.4) and 2.2 years (0.4-NE), respectively, compared to HPV33-: 3.8 years (3.3-7.8) or other HPV type-infected: 8.2 years (6.0-NE) CIN3+.
  
  
  CONCLUSIONS
  Routine post-conization hr-HPV DNA testing together with cervical cytology may provide a better prediction for potential recurrent disease. Further, primary prevention through adolescent vaccination may prevent CIN2+ and its recurrence.
authors.affiliation: Department of Pathology, Haukeland University Hospital, Norway; The Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway. Electronic address: olav.vintermyr@helse-bergen.no.
authors.forename: O K
authors.initials: OK
authors.lastname: Vintermyr
authors.affiliation: Institute of Clinical Medicine, University of Bergen, Bergen, Norway; Women's Clinic, Haukeland University Hospital, Bergen, Norway.
authors.forename: O
authors.initials: O
authors.lastname: Iversen
authors.affiliation: Abbvie AS, Norway.
authors.forename: S
authors.initials: S
authors.lastname: Thoresen
authors.affiliation: DDL Diagnostic Laboratory, Rijswijk, The Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: Quint
authors.affiliation: DDL Diagnostic Laboratory, Rijswijk, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Molijn
authors.affiliation: 4Clinics, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: de Souza
authors.affiliation: GlaxoSmithKline Vaccines, Wavre, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Rosillon
authors.affiliation: GlaxoSmithKline Vaccines, Wavre, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Holl
mesh_terms: D000328:Adult; D000368:Aged; D052685:Alphapapillomavirus / Q000235:genetics*; D019092:Conization; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics; D052161:Human papillomavirus 18 / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000821:virology*; D009664:Norway; D030361:Papillomavirus Infections / Q000821:virology*; D012042:Registries; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000601:surgery / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000821:virology*
chemical_list: D004279:DNA, Viral
keywords: Cervical intraepithelial neoplasia; Conization; High-risk HPV; Human papillomavirus; Recurrence