title: p16 staining has limited value in predicting the outcome of histological low-grade squamous intraepithelial lesions of the cervix.
abstract: In order to evaluate the usefulness of p16 staining in predicting the outcome of histological low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) we prospectively recruited all the patients referred to colposcopy from 2003 to 2011 due to abnormal screening test results and diagnosed with LSIL/CIN1 at biopsy (n=507). All biopsies were stained for p16 and re-evaluated after three years by the same gynecological pathologist using the LAST criteria. Follow-up was conducted every 6 months and included a Pap test (liquid-based cytology), high-risk human papillomavirus testing (Hybrid Capture 2 test), and colposcopy. The mean follow-up was 28 months. An outcome diagnosis of HSIL was defined as a histological diagnosis of high-grade SIL/CIN (HSIL/CIN2-3). The diagnosis of LSIL/CIN1 was confirmed in 416 out of 507 biopsies (82%), whereas 58 (11%) were reclassified as negative and 33 (6%) as HSIL/CIN2-3. During follow-up, 86/507 women initially diagnosed with LSIL/CIN1 (17%) showed an outcome diagnosis of HSIL/CIN2-3, with the rate of HSIL final diagnosis of 3% (2/58) in the women with biopsies reclassified as negative, 17% (70/416) in the group with confirmed LSIL and 42% (14/33) in the women with biopsies reclassified as HSIL (P<0.001). p16 was positive in 245/507 patients (48%) and in 210/416 patients (50%) with confirmed LSIL/CIN1 at re-evaluation. Although positive p16 immunostaining was associated with risk of HSIL/CIN2-3 outcome in the multivariate analysis (Hazard ratio (HR) 1.9; 95% confidence interval (CI): 1.2-3.1; P=0.009) in the overall group of patients with LSIL/CIN1, this association was not verified in the subset of patients with confirmed LSIL/CIN1 after re-evaluation (HR: 1.6; 95% CI: 0.9-2.6; P=0.095). In conclusion, in LSIL/CIN1 lesions p16 should be limited to equivocal cases in which HSIL/CIN2 is included in the differential diagnosis since it has low value in clinical practice as a marker of progression of LSIL/CIN1.
authors.affiliation: Department of Pathology, ISGlobal, Barcelona Centre For International. Health Research (CRESIB), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Amaia
authors.initials: A
authors.lastname: Sagasta
authors.affiliation: Department of Pathology, ISGlobal, Barcelona Centre For International. Health Research (CRESIB), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Paola
authors.initials: P
authors.lastname: Castillo
authors.affiliation: Department of Pathology, ISGlobal, Barcelona Centre For International. Health Research (CRESIB), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Adela
authors.initials: A
authors.lastname: Saco
authors.affiliation: Department of Obstetrics and Gynecology, IDIBAPS-Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Aureli
authors.initials: A
authors.lastname: Torné
authors.affiliation: Department of Pathology, ISGlobal, Barcelona Centre For International. Health Research (CRESIB), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Roser
authors.initials: R
authors.lastname: Esteve
authors.affiliation: Department of Pathology, ISGlobal, Barcelona Centre For International. Health Research (CRESIB), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Marimon
authors.affiliation: Department of Pathology, ISGlobal, Barcelona Centre For International. Health Research (CRESIB), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Ordi
authors.affiliation: Department of Obstetrics and Gynecology, IDIBAPS-Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Del Pino
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D065006:Papanicolaou Test; D011379:Prognosis; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000378:metabolism / Q000473:pathology*; D014626:Vaginal Smears; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins