title: Human papillomavirus oncogene mRNA testing for the detection of anal dysplasia in HIV-positive men who have sex with men.
abstract: BACKGROUND
  Anal human papillomavirus (HPV) infection and anal dysplasia are frequent in HIV-positive men who have sex with men (HIV+MSM), and progression of low-grade (LSIL) to high-grade squamous intraepithelial lesions (HSIL) or anal cancer (AC) occurs faster than in HIV-negative individuals. High-risk (HR)-HPV-E6/E7 oncogene mRNA testing has a higher specificity and a higher positive predictive value (PPV) than HR-HPV-DNA testing for detecting high-grade cervical lesions.
  
  
  OBJECTIVE
  To evaluate the diagnostic accuracy of the NucliSENS-EasyQ HPV1.1 E6/E7-mRNA-assay for the detection of anal dysplasia in HIV+MSM.
  
  
  METHODS
  289 intraanal swabs from HIV+MSM participating in a screening program that included anal cytology, high-resolution anoscopy and histology were analyzed. HR-HPV-DNA detection was performed by PCR and hybridization using a bead-based multiplex genotyping assay. E6/E7-mRNA detection of HR-HPV-types 16, 18, 31, 33 and 45 was performed using the NucliSENS-EasyQ assay.
  
  
  RESULTS
  269 swabs had valid results in both test formats (111 normal, 10 ASCUS, 105 LSIL, 42 HSIL, 1 AC). For the detection of LSIL+(LSIL+HSIL+cancer) sensitivity, specificity, negative predictive value (NPV) and PPV were 80.4%, 26.4%, 52.5%, and 57.2% for HR-HPV-DNA testing, respectively, compared to 75.7%, 57.9%, 66.0% and 68.7% for E6/E7-mRNA testing. The respective values for the detection of HSIL/cancer were 95.3%, 26.1%, 96.7%, 19.7% for HR-HPV-DNA and 95.3%, 46.0%, 98.1%, 25.2% for E6/E7-mRNA detection.
  
  
  CONCLUSIONS
  Compared to HR-HPV-DNA detection, E6/E7-mRNA testing has an increased specificity (approximately two-fold), similar sensitivity and higher NPV and PPV for the detection of low- and high-grade anal dysplasia in HIV+MSM.
authors.affiliation: Institute of Virology, National Reference Center for Papilloma- and Polyomaviruses, University of Cologne, Fuerst-Pueckler-Strasse 56, 50935 Koeln, Germany.
authors.forename: Steffi
authors.initials: S
authors.lastname: Silling
authors.forename: Alexander
authors.initials: A
authors.lastname: Kreuter
authors.forename: Martin
authors.initials: M
authors.lastname: Hellmich
authors.forename: Jochen
authors.initials: J
authors.lastname: Swoboda
authors.forename: Herbert
authors.initials: H
authors.lastname: Pfister
authors.forename: Ulrike
authors.initials: U
authors.lastname: Wieland
mesh_terms: D001003:Anal Canal / Q000473:pathology / Q000821:virology; D001005:Anus Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology; D004279:DNA, Viral / Q000032:analysis; D015658:HIV Infections / Q000150:complications* / Q000453:epidemiology; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D050725:Papillomavirus E7 Proteins / Q000235:genetics; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000453:epidemiology / Q000821:virology; D011230:Precancerous Conditions / Q000175:diagnosis / Q000453:epidemiology / Q000473:pathology; D011237:Predictive Value of Tests; D015995:Prevalence; D012333:RNA, Messenger / Q000235:genetics; D011933:Reagent Kits, Diagnostic; D012680:Sensitivity and Specificity
chemical_list: D004279:DNA, Viral; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D011933:Reagent Kits, Diagnostic