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J Natl Cancer Inst. 2015 Sep 15;107(12):djv257. doi: 10.1093/jnci/djv257. Print 2015 Dec.

p16/Ki-67 Dual Stain Cytology for Detection of Cervical Precancer in HPV-Positive Women.

Author information

1
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD (NW, MS, SNW, CB); Kaiser Permanente TPMG Regional Laboratory, Berkeley, CA (BF, ES, DT, NP, TL); Global Coalition Against Cervical Cancer, Arlington, VA (PEC); Albert Einstein College of Medicine, Bronx, NY (PEC); Division of Gynecologic Oncology, Kaiser Permanente Medical Care Program, Oakland, CA (WK). wentzenn@mail.nih.gov.
2
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD (NW, MS, SNW, CB); Kaiser Permanente TPMG Regional Laboratory, Berkeley, CA (BF, ES, DT, NP, TL); Global Coalition Against Cervical Cancer, Arlington, VA (PEC); Albert Einstein College of Medicine, Bronx, NY (PEC); Division of Gynecologic Oncology, Kaiser Permanente Medical Care Program, Oakland, CA (WK).

Abstract

BACKGROUND:

Human papillomavirus (HPV)-based cervical cancer screening requires triage markers to decide who should be referred to colposcopy. p16/Ki-67 dual stain cytology has been proposed as a biomarker for cervical precancers. We evaluated the dual stain in a large population of HPV-positive women.

METHODS:

One thousand five hundred and nine HPV-positive women screened with HPV/cytology cotesting at Kaiser Permanente California were enrolled into a prospective observational study in 2012. Dual stain cytology was performed on residual Surepath material, and slides were evaluated for dual stain-positive cells. Disease endpoints were ascertained from the clinical database at KPNC. We evaluated the clinical performance of the assay among all HPV-positive women and among HPV-positive, cytology-negative women. We used internal benchmarks for clinical management to evaluate the clinical relevance of the dual stain assay. We evaluated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the dual stain compared with Pap cytology. All statistical tests were two-sided.

RESULTS:

The dual stain had lower positivity (45.9%) compared with cytology at an ASC-US threshold (53.4%). For detection of CIN2+, the dual stain had similar sensitivity (83.4% vs 76.6%, P = .1), and statistically higher specificity (58.9% vs 49.6%, P < .001), PPV (21.0% vs 16.6%, P < .001), and NPV (96.4% vs 94.2%, P = .01) compared with cytology. Similar patterns were observed for CIN3+. Women with a positive test had high enough risk for referral to colposcopy, while the risk for women with negative tests was below a one-year return threshold based on current US management guidelines.

CONCLUSION:

Dual stain cytology showed good risk stratification for all HPV-positive women and for HPV-positive women with normal cytology. Additional follow-up is needed to determine how long dual stain negative women remain at low risk of precancer.

PMID:
26376685
PMCID:
PMC4675094
DOI:
10.1093/jnci/djv257
[Indexed for MEDLINE]
Free PMC Article

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