title: Association of human papillomavirus L1 capsid protein with koilocytosis, expression of p16, and Ki-67, and its potential as a prognostic marker for cervical intraepithelial neoplasia.
abstract: OBJECTIVE
  To study the relationship between human papillomavirus (HPV) L1 capsid protein (L1) and koilocytosis on ThinPrep cytology tests (TCTs) and the association of HPV L1 with p16 and Ki-67 expression in their corresponding biopsies.
  
  
  METHODS
  TCTs of 75 patients with high-risk HPV infection were studied for cytologic features of koilocytosis and for HPV L1 expression using combined detection of in situ hybridization and immunocytochemistry. All TCTs had follow-up biopsies on which p16 and Ki-67 were confirmed by immunostaining.
  
  
  RESULTS
  Of 75 TCTs, 45 expressed HPV L1, while 23 displayed koilocytosis. All TCTs with koilocytosis expressed HPV L1. HPV L1 was lost in 23.3% of cervical intraepithelial neplasia (CIN) I, 16.7% of CIN II, and 60% of CIN III or higher (carcinoma in situ including suspected minor infiltration), categorized by biopsy, and the difference among CIN grades was statistically significant (chi2, p = 0.015). Expression scores of p16 and Ki-67 were higher in L1 negative cases than in positive cases (1.63 vs. 1.54 for p16; 1.53 vs. 1.32 for Ki-67); however, the difference was not significant (Mann-Whitney test: p = 0.57 for p16, p = 0.27 for Ki-67).
  
  
  CONCLUSIONS
  HPV L1 expression was significantly associated with koilocytosis on TCT, and loss of L1 was associated with increase in CIN grade but not with p16 or Ki-67 expression. Our study suggests that HPV L1 is a more sensitive method than koilocytosis for detecting active HPV infection. Detection of HPV L1 on TCTs of high-risk HPV-infected patients can be helpful in risk assessment and prognostic prediction of CIN.
authors.affiliation: Department of Pathology, Beijing Hospital, Beijing, China. lanchen67@hotmail.com
authors.forename: Lan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pathology, Beijing Hospital, Beijing, China.
authors.forename: Ming-Jun
authors.initials: MJ
authors.lastname: Sun
authors.affiliation: Department of Gynecology, Beijing Hospital, Beijing, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Shi
authors.affiliation: Department of Pathology, Beijing Hospital, Beijing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Pathology, Beijing Hospital, Beijing, China.
authors.forename: Dong-Ge
authors.initials: DG
authors.lastname: Liu
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor; D001706:Biopsy; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D003581:Cytodiagnosis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D052162:Human papillomavirus 16 / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis* / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000378:metabolism; D011379:Prognosis; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D036022:Capsid Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins