title: p16 INK4a immunostaining identifies occult CIN lesions in HPV-positive women.
abstract: To evaluate whether p16 staining could help to recognize underestimated cervical intraepithelial neoplasia (CIN) in women positive for high-risk human papillomavirus (HR-HPV) with negative biopsy. Out of 1,259 women undergoing a histologic study and a simultaneous HR-HPV detection using the Hybrid Capture 2 test, we selected all patients testing positive for HR-HPV and having a negative biopsy (n=139), as well as all women testing negative for HR-HPV with a biopsy of either CIN 1 (26 cases) or CIN 2 to 3 (11 cases). Of the remaining 1,083 women, we randomly selected for the purpose of controls, 50 cases negative for HR-HPV with negative biopsy and 100 cases positive for HR-HPV and with biopsy of CIN (50 CIN 1, 50 CIN 2-3). In all cases, immunohistochemical staining for p16 and a second evaluation of the initial biopsy was carried out. Thirty-four out of 139 biopsies (24.5%) testing positive for HR-HPV but having a negative biopsy were positive for p16. Thirty of these cases (21.6%) were classified as harboring a CIN (11 CIN 1, 19 CIN 2/3) after reevaluation. Both the number of cases reclassified as CIN of any grade, or as CIN 2/3, were significantly higher for cases with HR-HPV load above 100 relative light unit (P<0.005). Particular attention should be paid to biopsies from patients having positive Hybrid Capture 2. The risk of harboring undetected CIN of any type or CIN 2/3 is significantly higher for patients with high HR-HPV load. Immunostaining with p16 should be considered as a highly desirable addition to the histologic evaluation of cervical biopsy specimens in HR-HPV-positive women.
authors.affiliation: Department of Pathology, School of Medicine, Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain. jordi@clinic.ub.es
authors.forename: Jaume
authors.initials: J
authors.lastname: Ordi
authors.forename: Sònia
authors.initials: S
authors.lastname: Garcia
authors.forename: Marta
authors.initials: M
authors.lastname: del Pino
authors.forename: Stefania
authors.initials: S
authors.lastname: Landolfi
authors.forename: Immaculada
authors.initials: I
authors.lastname: Alonso
authors.forename: Llorenç
authors.initials: L
authors.lastname: Quintó
authors.forename: Aureli
authors.initials: A
authors.lastname: Torné
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16