Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Jul 31;10(7):e0134445.
doi: 10.1371/journal.pone.0134445. eCollection 2015.

The Accuracy of p16/Ki-67 and HPV Test in the Detection of CIN2/3 in Women Diagnosed with ASC-US or LSIL

Júlio C Possati-Resende  1 , José H T G Fregnani  2 , Ligia M Kerr  3 , Edmundo C Mauad  1 , Adhemar Longatto-Filho  4 , Cristovam Scapulatempo-Neto  5
Affiliations

The Accuracy of p16/Ki-67 and HPV Test in the Detection of CIN2/3 in Women Diagnosed with ASC-US or LSIL

Júlio C Possati-Resende et al. PLoS One. .

Abstract

The objective of this study was to compare the accuracies of double staining for p16/Ki-67 and the molecular test for high-risk HPV (hr-HPV) to identify high-grade cervical intraepithelial neoplasia (CIN2/CIN3) in women with cervical cytology of atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL). Data were collected from 201 women who underwent cervical cytology screening in the Barretos Cancer Hospital and their results were categorized as ASC-US (n=96) or LSIL (n=105). All patients underwent colposcopy with or without cervical biopsy for diagnosis of CIN2/CIN3. The hr-HPV test (Cobas 4800 test) and immunocytochemistry were performed to detect biomarkers p16/Ki-67 (CINtec PLUS test). Two samples (1 ASC-US/1 LSIL) were excluded from the analysis due to inconclusive results of the histologic examination. There were 8 cases of CIN2/CIN3 among 95 women with ASC-US (8.4%), and 23 cases of CIN2/CIN3 among 104 women with LSIL (22.1%). In the group of women with ASC-US, the sensitivity and specificity in diagnosing CIN2/CIN3 were 87.5% and 79.5% for the HPV test and 62.5% and 93.1% for p16/Ki-67. Among women with LSIL, the sensitivity and specificity in the diagnosis of CIN2/CIN3 were 87% and 34.7% for the HPV test and 69.6% and 75.3% for immunocytochemistry. Superior performance was observed for p16/Ki-67 double staining, especially among women under 30 for whom the test had an area under the ROC curve of 0.762 (p<0.001). Both p16/Ki-67 double staining and the hr-HPV DNA test had similar performance in predicting high-grade cervical intraepithelial neoplasia among women with ASC-US. The best performance was observed in women aged >30 years. In younger women (≤30 years) with LSIL, p16/Ki-67 had greater accuracy in identifying precursor lesions. Among women >30 years diagnosed with LSIL, the two methods showed similar performance.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flowchart of the colposcopic examination and research p16/Ki-67 and hr-HPV.
ASC-US: atypical squamous cells of undetermined significance; LSIL: low-grade squamous intraepithelial lesion; EC: endocervical curettage.
Fig 2
Fig 2. Examples of positive tests for Ki-67 (red) and p16 (brown).
(A) and (D), 200x magnification; (B) and (C), 400x magnification.
Fig 3
Fig 3. Correlation between cervical cytology and colposcopy and histological findings.
CIN1, 2, 3: cervical intraepithelial neoplasia grade 1, 2 and 3; ASC-US: atypical squamous cells of undetermined significance; LSIL: low-grade squamous intraepithelial lesion. (*) Two cases with inconclusive biopsies (1 ASC-US and 1 LSIL) were excluded.
Fig 4
Fig 4. hr-HPV test according to the colpo-histological diagnosis.
HPV-16: positive cytological samples for subtype HPV-16. HPV-18: positive cytological samples for subtype HPV-18. Twelve Other HPV subtypes: positive cytology samples for one or more subtypes of HPV belonging to group 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. CIN 1, 2, 3: cervical intraepithelial neoplasia grade 1, 2 and 3.
See this image and copyright information in PMC

References

    1. Sankaranarayanan R, Black RJ, Parkin DM. Cancer survival in developing countries IARC Scientific Publications N°. 15. Lyon: IARC Press; 1988. - PubMed
    1. Nanda K, McCrory DC, Myers ER, Bastian LA, Hasselblad V, Hickey JD, et al. Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: a systematic review. Ann Intern Med. 2000;132(10):810–9. - PubMed
    1. Mitchell MF, Schottenfeld D, Tortolero-Luna G, Cantor SB, Richards-Kortum R. Colposcopy for the diagnosis of squamous intraepithelial lesions: a meta-analysis. Obstet Gynecol. 1998;91(4):626–31. - PubMed
    1. Allen K, Holladay EB. Risk Management for the Cytology Laboratory. Raleigh, NC: American Society for Cytotechnology; 2002.
    1. Sawaya GF, Grimes DA. New technologies in cervical cytology screening: a word of caution. Obstet Gynecol. 1999;94(2):307–10. - PubMed

MeSH terms