title: p16(INK4A) is a surrogate biomarker for a subset of human papilloma virus-associated dysplasias of the uterine cervix as determined on the Pap smear.
abstract: Recently, p16(INK4A) has been identified as a biomarker for human papilloma virus (HPV)-induced dysplastic lesions of the cervix and it has been suggested that it may be a useful diagnostic aid for these lesions. This study therefore was performed to determine the utility of p16 expression in a series of Papanicolaou (Pap) smears collected in liquid medium and to determine its benefit, if any, over HPV testing. One hundred seven cases, including 23 negative cases, 34 with low-grade squamous intraepithelial lesion (LSIL), 16 with high-grade squamous intraepithelial lesion (HSIL), 29 with atypical squamous cells of uncertain significance (ASC-US), and 5 cases with ASC suspicious for HSIL (ASC-H), were evaluated for both p16 expression and HPV DNA. We observed p16 expression in only 36% of all cases with abnormal cytology (30/84) and in 40% of all cases associated with high-risk HPV. The highest rate of positivity (80%) and the highest levels of expression (more than three to five positive cells/10x field) were seen in HSIL. Similar results were observed with ASC-H cases. This suggests that in equivocal cases, p16 may be used for confirmation of the diagnosis. On the other hand, p16 positivity was noted in only 21% of LSIL and ASC-US cases. This raises the interesting possibility, given that only a minority of LSIL cases progress on to higher-grade lesions, that p16 might be useful for triaging these patients for closer follow-up and/or further evaluation. Additional studies are required for confirmation.
authors.affiliation: Department of Pathology, Cedars Sinai Medical Center, Los Angeles, California 90048, USA. BoseS@cshs.org
authors.forename: Shikha
authors.initials: S
authors.lastname: Bose
authors.forename: Helen
authors.initials: H
authors.lastname: Evans
authors.forename: Liz
authors.initials: L
authors.lastname: Lantzy
authors.forename: Karen
authors.initials: K
authors.lastname: Scharre
authors.forename: Evette
authors.initials: E
authors.lastname: Youssef
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000175:diagnosis* / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D065006:Papanicolaou Test; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis*; D011230:Precancerous Conditions / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000737:chemistry / Q000175:diagnosis* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000821:virology; D014626:Vaginal Smears
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral