title: Triage of HR-HPV positive women with minor cytological abnormalities: a comparison of mRNA testing, HPV DNA testing, and repeat cytology using a 4-year follow-up of a population-based study.
abstract: OBJECTIVE
  Expression of the viral E6/E7 oncogenes of high-risk human papillomaviruses (HR-HPV) is necessary for malignant conversion and maintenance in cervical tissue. In order to determine whether HR-HPV E6/E7 mRNA testing more effectively predicts precancerous lesions and invasive cervical cancer than HR-HPV DNA testing, we aimed to compare triage using HR-HPV E6/E7 mRNA testing by APTIMA HPV Assay (APTIMA) to HPV16 DNA testing, HPV16/18 DNA testing, and repeat cytology.
  
  
  METHODS
  Liquid-based (PreservCyt) cell samples were obtained from HR-HPV-positive women diagnosed with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) within the framework of the population-based cervical cancer screening program in Stockholm, Sweden. Samples were tested for HR-HPV E6/E7 mRNA by APTIMA (Gene-Probe Inc., San Diego, CA, USA). Women were followed up for 4 years after the index cytology via medical and laboratory records, and the Stockholm Oncology Center.
  
  
  RESULTS
  Nine of 25 (36%) women in the ASCUS group, and 64 of 180 (36%) women in the LSIL group developed cervical intraepithelial neoplasia (CIN) grade 2 or worse during 4 years of follow-up. 162 (74%) women were APTIMA-positive, and APTIMA had the highest sensitivity to predict CIN2 or worse and CIN3 or worse in the ASCUS (77.8% and 100%) and LSIL (78.1 and 75.8%) groups, although specificity was insufficient (<50%). HPV16 DNA testing and repeat cytology were more specific than APTIMA.
  
  
  CONCLUSIONS
  The results of this population-based study with comprehensive follow-up support the use of APTIMA as a triage test for women with ASCUS. More focused investigation is required for women with LSIL.
authors.affiliation: Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Persson
authors.affiliation: Department of Medical Epidemiology and Biostatistics Karolinska Institutet, Stockholm, Sweden.
authors.forename: K Miriam
authors.initials: KM
authors.lastname: Elfström
authors.affiliation: Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Sophia
authors.initials: S
authors.lastname: Brismar Wendel
authors.affiliation: Department of Medical Epidemiology and Biostatistics Karolinska Institutet, Stockholm, Sweden ; Cancer Registry of Norway, Oslo, Norway ; Department of Community Medicine, Universitetet i Tromso, Tromso, Norway ; Samfundet Folkhälsan, Genetic Epidemiology Group, Folkhälsan Research Center, University of Helsinki, Helsinki, Finland.
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
authors.affiliation: Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Sonia
authors.initials: S
authors.lastname: Andersson
mesh_terms: D000328:Adult; D002584:Cervix Uteri / Q000473:pathology; D003584:Cytological Techniques; D004847:Epithelial Cells / Q000473:pathology / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D061809:Human Papillomavirus DNA Tests; D006801:Humans; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014218:Triage / Q000379:methods*; D055815:Young Adult
chemical_list: D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger