title: Which test is a better strategy to determine the outcome of atypical glandular cell-categorized Pap smears? Immunocytochemical p16INK4A expression or human papillomavirus test--a retrospective cohort study.
abstract: OBJECTIVE
  This study was to correlate high-risk human papillomavirus (HR-HPV) viral load to p16(INK4A) (p16) expression in atypical glandular cell (AGC)-categorized Pap smears with follow-up biopsies for elucidating their relationships.
  
  
  METHODS
  We enrolled 36 AGC-categorized Pap smears with subsequent follow-up biopsies. HR-HPV viral load was determined by Hybrid Capture II assay in each AGC-diagnosed Pap smear. Both smears and biopsies were immunostained with a primary anti-p16 antibody, clone E6H4. Correlations between HR-HPV viral load in each AGC-diagnosed Pap smear and p16 expression of smears with follow-up biopsies were performed.
  
  
  RESULTS
  Comparative analysis of two tests disclosed both consistencies and discrepancies. There were significant differences (P=0.02) between negative or weak p16 expression of Pap smears with the presence of reactive lesion or LSILs/CIN1s in follow-up biopsies and negative HR-HPV viral load. However, no significant difference (P=0.317) was found between p16 expression of Pap smears with the presence of HSIL/CIN2, 3 and AIS or adenocarcinoma in follow-up biopsies and high HR-HPV viral load. In addition, there were significant differences (P=0.012) in specificity, but no significant differences were found in sensitivity (P=0.604), positive and negative predictive value (P=0.066 and 0.264) between p16 immunoexpression and HR-HPV viral load.
  
  
  CONCLUSIONS
  Pathogenic activity of HR-HPV was indicated by p16 expression on smears and tissue sections, which appears to be a better strategy than HR-HPV viral load test for the detection of clinically insignificant lesions from AGC-categorized Pap smears.
authors.affiliation: School of Dentistry, National Yang-Ming University, and Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Su-Feng
authors.initials: SF
authors.lastname: Chen
authors.forename: Shih-Fang
authors.initials: SF
authors.lastname: Yang
authors.forename: Tang-Yuan
authors.initials: TY
authors.lastname: Chu
authors.forename: Hung-Cheng
authors.initials: HC
authors.lastname: Lai
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Lin
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Bai
authors.forename: Shin
authors.initials: S
authors.lastname: Nieh
mesh_terms: D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D065006:Papanicolaou Test; D027383:Papillomaviridae / Q000254:growth & development / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D012189:Retrospective Studies; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology; D014626:Vaginal Smears; D019562:Viral Load
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16