Role of p16(INK4a) cytology testing as an adjunct to enhance the diagnostic specificity and accuracy in human papillomavirus-positive women within an organized cervical cancer screening program.
OBJECTIVE
We evaluated the performance of cytologic p16(INK4a) (p16) immunostaining within a cervical cancer screening program for the categories of atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LS after triage with high-risk human papillomavirus (HR-HPV) testing and atypical squamous cells, cannot exclude high-grade intraepithelial squamous lesion (ASC-H) and high-grade squamous intraepithelial lesion (HSIL). We also verified whether the routine introduction of p16 staining might enhance the specificity and positive predictive value (PPV) for cervical intraepithelial neoplasia grade 2 or higher (CIN2+) lesions predicted by a cytological screening test.


METHODS
Performance of the p16 cytology test was estimated in 578 cytological samples, of which 213 were HR-HPV+ ASC-US, 186 were HR-HPV+ LSIL, 74 were ASC-H, 56 were HSIL-CIN2 and 49 were HSIL-CIN3. All samples had histological follow-up.


RESULTS
In the ASC-US category, p16 sensitivity was 91% for CIN2+ and 100% for CIN3, while specificity was 64 and 58%, respectively, negative predictive value (NPV) was 96 and 100%, respectively, and PPV was 39%. In the LSIL category, sensitivity was 77 and 75%, respectively, for CIN2+ and CIN3, while specificity was 64 and 57%, NPV was 93 and 98% and PPV was 30%. Sensitivity for ASC-H and HSIL-CIN3 was 100% for CIN2+ and CIN3, while for HSIL-CIN2 it was 91 and 95%, respectively; NPV for ASC-H was 100%, and for HSIL-CIN2 it was 43 and 86%, respectively. Follow-up examinations of 8 cases diagnosed as p16+ ASC-H and HSIL-CIN3, but histologically negative or CIN1 on the first biopsy, showed 4 CIN2 and 4 CIN3 lesions.


CONCLUSIONS
Sensitivity, specificity, PPV and NPV confirm the importance of the utilization of p16 in the categories ASC-US and LSIL after triage with an HR-HPV test. In the ASC-H and HSIL-CIN3 lesions, p16 was shown to be an excellent marker for picking up CIN2+ lesions, especially in cases with cytohistological discordance.
Azienda Sanitaria Regionale dell'Umbria USL2, U.O.C. Diagnostica di Laboratorio, U.O. Citologia, Perugia, Italia.
Daniela
D
Gustinucci
Basilio
B
Passamonti
Elena
E
Cesarini
Daniela
D
Butera
Emiliano Antonio
EA
Palmieri
Simonetta
S
Bulletti
Angela
A
Carlani
Maria
M
Staiano
Maria Rosaria
MR
D'Amico
Valentina
V
D'Angelo
Eugenio
E
Di Dato
Nadia
N
Martinelli
Morena
M
Malaspina
Nicoletta
N
Spita
Beatrice
B
Tintori
Franco
F
Fulciniti
D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D002584:Cervix Uteri / Q000737:chemistry / Q000473:pathology / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis* / Q000502:physiology; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D027383:Papillomaviridae / Q000502:physiology; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology
D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16