title: Usefulness of liquid-based cytology specimens for the immunocytochemical study of p16 expression and human papillomavirus testing: a comparative study using simultaneously sampled histology materials.
abstract: BACKGROUND
  In cervical lesions, the overexpression of p16 is reported to be closely associated with high-risk human papillomavirus (HPV) infection. The objective of the current study was to confirm the usefulness of liquid-based cervical specimens for p16 staining as well as tissue sections.
  
  
  METHODS
  A total of 98 patients with cervical lesions were entered into the current study. After the cytologic examination using liquid-based cervical smears, the same slides were immunostained for p16 and were compared with slides of simultaneously obtained, immunohistologically stained tissue sections. Moreover, the status of the HPV infection was examined by polymerase chain reaction using residual cytologic samples.
  
  
  RESULTS
  Using liquid-based Pap smears, 98 cases were diagnosed as atypical squamous cells of undetermined significance (38 cases), low-grade squamous intraepithelial lesion (12 cases), high-grade squamous intraepithelial lesion (HSIL) (33 cases), and invasive carcinoma (15 cases). The concordance rate between the cytologic and histologic diagnoses was found to be higher in high-grade lesions compared with low-grade lesions. Immunohistochemistry revealed that all HSIL and invasive carcinoma cases contained p16-positive cells in the liquid-based Pap smears and diffuse p16 staining was observed in all high-grade lesions with greater than CIN Grade 3 cervical intraepithelial neoplasia except for two adenocarcinoma cases. Of the 98 cases, 60 were found to be positive for high-risk HPV and 55 of these 60 HPV-positive cases were found to be p16 positive on cytologic examination. There were 16 cases that demonstrated marked discrepancies between the cytologic and histologic diagnoses.
  
  
  CONCLUSIONS
  The results of the current study confirmed that the immunohistochemical detection of p16 was more sensitive and specific than HPV status in cervical lesions using a liquid-based method as well as tissue samples, suggesting that p16 should be used as a satisfactory biomarker for the primary screening of cervical cytology.
authors.affiliation: Department of Tumor Pathology, Gunma University Graduate School of Medicine, Gunma, Japan. toyosida@health.gunma-u.ac.jp
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Toshio
authors.initials: T
authors.lastname: Fukuda
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sano
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kanuma
authors.forename: Nobuo
authors.initials: N
authors.lastname: Owada
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000328:Adult; D002277:Carcinoma / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D065006:Papanicolaou Test; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000473:pathology*; D014626:Vaginal Smears / Q000379:methods*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral