title: Comparing Papanicolau smear, visual inspection with acetic acid and human papillomavirus cervical cancer screening methods among HIV-positive women by immune status and antiretroviral therapy.
abstract: BACKGROUND
  A rigorous comparison of cervical cancer screening methods utilizing data on immune status, antiretroviral therapy (ART) and colposcopy-directed biopsy has not been performed among HIV-positive women.
  
  
  METHODS
  Between June and November 2009, 500 HIV-positive women were enrolled at an HIV treatment clinic in Nairobi, Kenya, and underwent Papanicolau (Pap) smear, visual inspection with acetic acid (VIA), human papillomavirus (HPV) and colposcopy-directed biopsy (gold standard). Positive Pap smear (ASCUS+, LSIL+, HSIL+), VIA, HPV and their combinations were compared with CIN2/3+. Sensitivity, specificity and AUC (sensitivity and 1-specificity) were compared using pairwise tests and multivariate logistic regression models that included age, CD4⁺ cell count and ART duration.
  
  
  RESULTS
  Of 500 enrolled, 498 samples were collected. On histology, there were 172 (35%) normal, 186 (37%) CIN1, 66 (13%) CIN2, 47 (9%) CIN3 and 27 (5%) indeterminate. Pap (ASCUS+) was the most sensitive screening method (92.7%), combination of both Pap (HSIL+) and VIA positive was the most specific (99.1%) and Pap (HSIL+) had the highest AUC (0.85). In multivariate analyses, CD4⁺ cell count of 350 cells/μl or less was associated with decreased HPV specificity (P = 0.002); ART duration of less than 2 years was associated with decreased HPV (P = 0.01) and VIA (P = 0.03) specificity; and age less than 40 years was associated with increased VIA sensitivity (P < 0.001) and decreased HPV specificity (P = 0.005).
  
  
  CONCLUSIONS
  Pap smear is a robust test among HIV-positive women regardless of immune status or ART duration. Results should be cautiously interpreted when using HPV among those younger, immunosuppressed or on ART less than 2 years, and when using VIA among those aged 40 years or more.
authors.affiliation: aDepartment of Global Health bDepartment of Medicine cDepartment of Epidemiology dDepartment of Biostatistics, University of Washington, Seattle, Washington, USA eInfections and Cancer Epidemiology Group, International Agency for Research on Cancer, Lyon, France fVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA gAga Khan University Hospital hKenyatta National Hospital iCoptic Hospital, Nairobi, Kenya. *Deceased.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Chung
authors.forename: Kevin P
authors.initials: KP
authors.lastname: McKenzie
authors.forename: Hugo
authors.initials: H
authors.lastname: De Vuyst
authors.forename: Barbra A
authors.initials: BA
authors.lastname: Richardson
authors.forename: Farzana
authors.initials: F
authors.lastname: Rana
authors.forename: Ritesh
authors.initials: R
authors.lastname: Pamnani
authors.forename: Julia W
authors.initials: JW
authors.lastname: Njoroge
authors.forename: Evans
authors.initials: E
authors.lastname: Nyongesa-Malava
authors.forename: Samah R
authors.initials: SR
authors.lastname: Sakr
authors.forename: Grace C
authors.initials: GC
authors.lastname: John-Stewart
authors.forename: Nelly R
authors.initials: NR
authors.lastname: Mugo
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D018791:CD4 Lymphocyte Count; D003127:Colposcopy / Q000379:methods; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology*; D006651:Histocytochemistry / Q000379:methods; D006801:Humans; D007630:Kenya; D008875:Middle Aged; D065006:Papanicolaou Test / Q000379:methods; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology; D014773:Virology / Q000379:methods; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents