Triaging HPV-positive women with p16/Ki-67 dual-stained cytology: Results from a sub-study nested into the ATHENA trial

Wright, Thomas; Behrens, Catherine M.; Ranger‐Moore, James; Rehm, Susanne; Sharma, Abha; Stoler, Mark H.; Ridder, Ruediger

doi:10.1016/j.ygyno.2016.10.031

Cited by 111 publications

(150 citation statements)

References 25 publications

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“…As a single detection of HPV DNA is not indicative of persistent infections, it is necessary to search for specific markers of the cell regulation problems that might lead to carcinogenesis, such as oncoproteins [1]. The tumor suppressor protein p16 and the proliferation marker Ki-67, when detected within the same cell, are indicative of a deregulation in the cell cycle that can eventually turn into a neoplasia [13,20,21]. Since p16 ends up regulating cell proliferation and the protein Ki-67 is a marker of this, both can be helpful markers of this deregulation.…”

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confidence: 99%

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Dual p16 and Ki-67 Expression in Liquid-Based Cervical Cytological Samples Compared to Pap Cytology Findings, Biopsies, and HPV Testing in Cervical Cancer Screening: A Diagnostic Accuracy Study

et al. 2018

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Objective: Our objective was to verify the sensitivity and specificity of dual immunocytochemistry staining for p16 and Ki-67 in liquid-based samples (the “dual” assay) for cervical lesion screening, compared to biopsy findings and human papillomavirus (HPV) DNA molecular detection. Study Design: Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values for the “dual immunocytochemistry assay” were calculated and compared to histopathological results and to high-risk HPV DNA detection in adult women or teenagers submitted to cervical cancer screening. Results: A total of 151 women were included. The majority (96.2%) of those with negative dual assay results had lower biopsy grades (p < 0.001). Women with cytology results suggestive of cervical cancer had positive dual immunocytochemistry assay results more frequently (p < 0.001), and these positive results were also significantly associated with biopsy findings (p < 0.001) and with high-risk genotype HPV infection (p = 0.007). Specificity and PPV for the dual assay were 0.972 (0.855–0.999) and 0.800 (0.284–0.995), respectively, and 1.000 (0.590–1.000) and 1.000 (0.631–1.000) for HPV detection. Conclusions: The dual immunocytochemistry assay had high specificity and PPV. It reveals a persistent HPV infection, avoiding the need for new tissue collections for biopsies or hybrid capture.

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confidence: 99%

“…Cervical cytology immunocytochemistry with "dual staining" (p16 plus Ki-67) could, therefore, be used as a triage for HPV-positive women with mildly abnormal smear results [13,20,[23][24][25][26][27][28][29][30][31][32][33]. This dual biomarker approach is morphology independent [27,34] and, therefore, has good reproducibility [34].…”

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confidence: 99%

Dual p16 and Ki-67 Expression in Liquid-Based Cervical Cytological Samples Compared to Pap Cytology Findings, Biopsies, and HPV Testing in Cervical Cancer Screening: A Diagnostic Accuracy Study

et al. 2018

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“…INK4a has been used for dual-staining with p16/Ki-67 cytology (p16/Ki-67); this would complement the low sensitivity of cytology and the low specificity of the HPV test for secondary prevention of CC [70][71][72].…”

Section: Ink4amentioning

confidence: 99%

Secondary Prevention of Uterine Cervical Cancer

Sato¹,

Itamochi²

2018

Cervical Cancer - Screening, Treatment and Prevention - Universal Protocols for Ultimate Control

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Secondary prevention by cervical cytology has clearly improved the mortality rate of uterine cervical cancer (CC) by enabling early detection and treatment of high-grade squamous intraepithelial lesion (HSIL) or cervical intraepithelial neoplasia (CIN), which is a precancerous lesion. In the past two decades, HPV-DNA testing, including HPV typing, has clearly brought about positive effects on secondary prevention of CC. However, in practice, CC remains a fatal disease and is the second leading cause of cancer deaths in women aged 20-39 years. Although elucidation of the mechanisms of HPV carcinogenesis and development of a prophylactic vaccine have made CC a preventable disease, eradication of CC is expected to take several decades. Therefore, primary screening to decrease the mortality rate of CC will remain important for a while. In addition, the clinical application of simple biomarkers to stratify HPV-positive women is important for maintenance of medical economy and avoidance of overtreatment in women in the reproductive age. Therefore, the development of an inexpensive therapy or vaccine that can be used worldwide is necessary to overcome cancer deaths due to CC.

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“…A retrospective sub-study based on the ATHENA trial patients analyzed the performance of dual-staining cytology and found it to be significantly more sensitive than cytology alone (74.9% vs. 51.9%; P < 0.0001) while having comparable specificity (74.1% vs.75%; P 5 0.3198). 40 A study from the Netherlands found it to have even higher specificity than cytology with genotyping. 41 The cost-effectiveness of dual-stain cytology triage was demonstrated in a model-based study from Belgium.…”

Section: Cytology Triagementioning

confidence: 99%

“…Another option that has been studied for triage of primary screened HPV‐positive women is the use of dual‐immunocytochemical staining for p16INK4a and ki‐67. A retrospective sub‐study based on the ATHENA trial patients analyzed the performance of dual‐staining cytology and found it to be significantly more sensitive than cytology alone (74.9% vs. 51.9%; P < 0.0001) while having comparable specificity (74.1% vs.75%; P = 0.3198) . A study from the Netherlands found it to have even higher specificity than cytology with genotyping .…”

Section: Introductionmentioning

confidence: 99%

Cervical cancer screening in the era of HPV vaccination: A review of shifting paradigms in cytopathology

Barroeta

Adhikari-Guragain

Grotkowski

2017

Diagnostic Cytopathology

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Significant changes in cervical cancer screening practice, guidelines, and prevention of cervical cancer have taken place in recent years including the raising of initial cervical cancer screening age, changes in frequency of cytology screening, and the adoption of high risk HPV and cytology co-testing for some patients; the introduction of the bivalent, quadrivalent, and 9-valent HPV vaccines; and the recent approval of high risk HPV testing as primary screening with the use of cytology as triage in positive cases. This review discusses the significance of primary HPV screening, the impact of HPV vaccination in the prevalence of cervical cancer and its precursors, the interplay between high risk HPV testing and vaccination, and the implications for clinical and cytological management. Future strategies for cervical screening in the post-vaccination era are also discussed.

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Triaging HPV-positive women with p16/Ki-67 dual-stained cytology: Results from a sub-study nested into the ATHENA trial

Cited by 111 publications

References 25 publications

Dual p16 and Ki-67 Expression in Liquid-Based Cervical Cytological Samples Compared to Pap Cytology Findings, Biopsies, and HPV Testing in Cervical Cancer Screening: A Diagnostic Accuracy Study

Dual p16 and Ki-67 Expression in Liquid-Based Cervical Cytological Samples Compared to Pap Cytology Findings, Biopsies, and HPV Testing in Cervical Cancer Screening: A Diagnostic Accuracy Study

Secondary Prevention of Uterine Cervical Cancer

Cervical cancer screening in the era of HPV vaccination: A review of shifting paradigms in cytopathology

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