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. 2024 Apr 1;28(2):124-130.
doi: 10.1097/LGT.0000000000000802. Epub 2024 Mar 2.

Recommendations for Use of p16/Ki67 Dual Stain for Management of Individuals Testing Positive for Human Papillomavirus

Megan A Clarke  1 , Nicolas Wentzensen  1 , Rebecca B Perkins  2 , Francisco Garcia  3 , Deborah Arrindell  4 , David Chelmow  5 , Li C Cheung  1 , Teresa M Darragh  6 , Didem Egemen  1 , Richard Guido  7 , Warner Huh  8 , Alexander Locke  9 , Thomas S Lorey  10 , Ritu Nayar  11 , Carolann Risley, Debbie Saslow  12 , Robert A Smith  13 , Elizabeth R Unger  14 , L Stewart Massad  15 ; Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee
Affiliations

Recommendations for Use of p16/Ki67 Dual Stain for Management of Individuals Testing Positive for Human Papillomavirus

Megan A Clarke et al. J Low Genit Tract Dis. .

Erratum in

Abstract

Objectives: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for dual stain (DS) testing with CINtec PLUS Cytology for use of DS to triage high-risk human papillomavirus (HPV)-positive results.

Methods: Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated according to DS results among individuals testing HPV-positive using data from the Kaiser Permanente Northern California cohort and the STudying Risk to Improve DisparitiES study in Mississippi. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Resource usage metrics were calculated to support decision-making. Risk estimates in relation to clinical action thresholds were reviewed and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through a vote by the Consensus Stakeholder Group.

Results: For triage of positive HPV results from screening with primary HPV testing (with or without genotyping) or with cytology cotesting, colposcopy is recommended for individuals testing DS-positive. One-year follow-up with HPV-based testing is recommended for individuals testing DS-negative, except for HPV16- and HPV18-positive results, or high-grade cytology in cotesting, where immediate colposcopy referral is recommended. Risk estimates were similar between the Kaiser Permanente Northern California and STudying Risk to Improve DisparitiES populations. In general, resource usage metrics suggest that compared with cytology, DS requires fewer colposcopies and detects cervical intraepithelial neoplasia grade 3 or worse earlier.

Conclusions: Dual stain testing with CINtec PLUS Cytology is acceptable for triage of HPV-positive test results. Risk estimates are portable across different populations.

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Conflict of interest statement

N.B. has served as a consultant for Dysis. M.E. has served as a consultant for Papivax, Merck, BD, and PDS. R.G. has served as a consultant for Inovio. D.H. has served as a consultant for Roche. W.H. has served as a consultant for Roche, SeeGene, and AstraZeneca. R.N. has participated in an educational meeting supported by Roche. D.C. has received stipends from ABOG and Medscape and is currently receiving project funding from ACOG. The other authors have declared they have no conflicts of interest.

References

    1. Perkins RB Guido RS Castle PE, et al. 2019 ASCCP Risk-Based Management Consensus Guidelines for abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis 2020;24:102–31. - PMC - PubMed
    1. Egemen D Perkins RB Clarke MA, et al. Risk-Based Cervical Consensus Guidelines: methods to determine management if less than 5 years of data are available. J Low Genit Tract Dis 2022;26:195–201. - PMC - PubMed
    1. Food and Drugs Administration . CINtec PLUS Cytology. 2019. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf19/P190024C.pdf. Accessed September 1, 2022.
    1. Clarke MA Cheung LC Castle PE, et al. Five-year risk of cervical precancer following p16/Ki-67 dual-stain triage of HPV-positive women. JAMA Oncol 2019;5:181–6. - PMC - PubMed
    1. Wentzensen N Clarke MA Bremer R, et al. Clinical evaluation of human papillomavirus screening with p16/Ki-67 dual stain triage in a large organized cervical cancer screening program. JAMA Intern Med 2019;179:881–8. - PMC - PubMed