title: Use of human papillomavirus DNA, E6/E7 mRNA, and p16 immunocytochemistry to detect and predict anal high-grade squamous intraepithelial lesions in HIV-positive and HIV-negative men who have sex with men.
abstract: BACKGROUND
  Men who have sex with men (MSM) are at high risk of having anal cancer. Anal high-grade squamous intraepithelial lesion (HSIL) is the precursor of anal cancer. We explored the use of different biomarkers associated with human papillomavirus (HPV) infection and HPV-mediated cell transformation to detect and predict HSIL among HIV-positive and HIV-negative MSM.
  
  
  RESULTS
  A total of 123 HIV-positive and 123 HIV-negative MSM were enrolled and followed for 12 months. High-resolution anoscopy (HRA) with biopsies were performed at every visit along with anal sample collection for cytology, high-risk HPV DNA genotyping, HPV E6/E7 mRNA, and p16 immunocytochemistry. Performance characteristics and area under the receiver operator characteristics curve were calculated for these biomarkers at baseline, and Cox regression compared the usefulness of these biomarkers in predicting incident HSIL. High-risk HPV DNA, E6/E7 mRNA, and p16 immunocytochemistry each identified 43-46% of MSM whose baseline test positivity would trigger HRA referral. E6/E7 mRNA had the highest sensitivity (64.7%) and correctly classified the highest number of prevalent HSIL cases. With the exception of p16 immunochemistry, most tests showed significant increases in sensitivity but decreases specificity versus anal cytology, while the overall number of correctly classified cases was not significantly different. Baseline or persistent type 16 and/or 18 HPV DNA was the only test significantly predicting incident histologic HSIL within 12 months in models adjusted for HIV status and low-grade squamous intraepithelial lesions at baseline.
  
  
  CONCLUSIONS
  Countries with a high HIV prevalence among MSM and limited HRA resources may consider using biomarkers to identify individuals at high risk of HSIL. E6/E7 mRNA had the highest sensitivity for prevalent HSIL detection regardless of HIV status, whereas type 16 and/or 18 HPV DNA performed best in predicting development of incident HSIL within 12 months.
authors.affiliation: The Thai Red Cross AIDS Research Centre, Bangkok, Thailand ; SEARCH, Bangkok, Thailand.
authors.forename: Nittaya
authors.initials: N
authors.lastname: Phanuphak
authors.forename: Nipat
authors.initials: N
authors.lastname: Teeratakulpisarn
authors.forename: Somboon
authors.initials: S
authors.lastname: Keelawat
authors.forename: Tippawan
authors.initials: T
authors.lastname: Pankam
authors.forename: Jiranuwat
authors.initials: J
authors.lastname: Barisri
authors.forename: Surang
authors.initials: S
authors.lastname: Triratanachat
authors.forename: Amornrat
authors.initials: A
authors.lastname: Deesua
authors.forename: Piyanee
authors.initials: P
authors.lastname: Rodbamrung
authors.forename: Jiratchaya
authors.initials: J
authors.lastname: Wongsabut
authors.forename: Patou
authors.initials: P
authors.lastname: Tantbirojn
authors.forename: Saranya
authors.initials: S
authors.lastname: Numto
authors.forename: Preecha
authors.initials: P
authors.lastname: Ruangvejvorachai
authors.forename: Praphan
authors.initials: P
authors.lastname: Phanuphak
authors.forename: Joel M
authors.initials: JM
authors.lastname: Palefsky
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kerr
mesh_terms: D000328:Adult; D001003:Anal Canal / Q000473:pathology / Q000821:virology*; D015415:Biomarkers / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D004847:Epithelial Cells / Q000473:pathology* / Q000821:virology; D060005:Genotyping Techniques; D018023:HIV Seronegativity; D006679:HIV Seropositivity / Q000150:complications*; D018451:Homosexuality, Male; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis* / Q000276:immunology; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D050725:Papillomavirus E7 Proteins / Q000235:genetics*; D015995:Prevalence; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012306:Risk
chemical_list: D015415:Biomarkers; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D009363:Neoplasm Proteins; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger