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

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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Novel concepts in cervical cancer screening: a comparison of VIA, HPV DNA test and p16INK4a/Ki-67 dual stain cytology in Western Kenya

Infectious Agents and Cancer ◽

10.1186/s13027-020-00323-6 ◽

2020 ◽

Vol 15 (1) ◽

Cited By ~ 3

Author(s):

Elkanah Omenge Orang’o ◽

Edwin Were ◽

Oliver Rode ◽

Kapten Muthoka ◽

Michael Byczkowski ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Screening Program ◽

Hpv Infection ◽

High Morbidity ◽

Ki 67 ◽

Dna Test ◽

Hpv Dna ◽

Triage Test

Abstract Background Screening of unvaccinated women remains essential to mitigate the high morbidity/mortality of cervical cancer. Here, we compared visual inspection with acetic acid (VIA), recommended by WHO as the most cost-effective screening approach in LMICs, with HPV-based screening, and usage of p16INK4a/Ki-67 dual stain cytology. Methods We prospectively enrolled women participating in a VIA-based cervical cancer screening program in two peri-urban health centers of Kenya. Consenting women had a VIA examination preceded by collection of a liquid-based cytology sample from the cervix stored in PreservCyt medium (Hologic®). Analysis of all samples included a hrHPV DNA test and evaluation of a p16INK4a /Ki-67 (CINtecPLUS®) dual stained slide that was prepared using the ThinPrep® 2000 Processor and evaluated by a pathologist trained in the methodology. Results In 701 of a total of 800 women aged 18–64 years, all three investigations were performed and data could be analyzed. The HPV, VIA and dual stain cytology positivity were 33%, 7%, and 2% respectively. The HPV positivity rate of VIA positive cases was 32%. The five most common HPV types were HPV16, 52, 68, 58 and 35. The OR among HIV infected women of an HPV infection, VIA positivity and positive dual stain cytology were 2.6 (95%CI 1.5–4.3), 1.9 (95%CI 0.89–4.4) and 3.4 (95%CI 1.07–10.9) respectively. The sensitivity of VIA to detect a p16INK4a/Ki-67 positive transforming infection was 13% (95%CI 2–38). Conclusions Primary HPV testing appears feasible and should be considered as a primary screening test also in LMICs. The poor sensitivity of VIA renders it unsuitable as a triage test for HPV positive women. The utility of p16INK4a/Ki-67 dual stain cytology as a triage test for HPV positive women in LMICs should be further studied.

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Novel concepts in cervical cancer screening. A comparison of VIA, HPV DNA test and p16INK4a/Ki-67 dual stain cytology in Western Kenya.

10.21203/rs.3.rs-39673/v2 ◽

2020 ◽

Author(s):

Elkanah Omenge Orang’o ◽

Edwin Were ◽

Oliver Rode ◽

Kapten Muthoka ◽

Michael Byczkowski ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Screening Program ◽

Hpv Infection ◽

High Morbidity ◽

Ki 67 ◽

Dna Test ◽

Hpv Dna ◽

Triage Test

Abstract Background: Screening of unvaccinated women remains essential to mitigate the high morbidity/mortality of cervical cancer. Here, we compared visual inspection with acetic acid (VIA), recommended by WHO as the most cost-effective screening approach in LMICs, with HPV-based screening, and usage of p16INK4a/Ki-67 dual stain cytology.Methods: We prospectively enrolled women participating in a VIA-based cervical cancer screening program in two peri-urban health centers of Kenya. Consenting women had a VIA examination preceded by collection of a liquid-based cytology sample from the cervix stored in PreservCyt medium (Hologic®). Analysis of all samples included a hrHPV DNA test and evaluation of a p16INK4a /Ki-67 (CINtecPLUS®) dual stained slide that was prepared using the ThinPrep® 2000 Processor and evaluated by a pathologist trained in the methodology.Results: In 701 of a total of 800 women aged 18-64 years, all three investigations were performed and data could be analyzed. The HPV, VIA and dual stain cytology positivity were 33%, 7%, and 2% respectively. The HPV positivity rate of VIA positive cases was 32%. The five most common HPV types were HPV16, 52, 68, 58 and 35. The OR among HIV infected women of an HPV infection, VIA positivity and positive dual stain cytology were 2.6 (95%CI 1.5-4.3), 1.9 (95%CI 0.89-4.4) and 3.4 (95%CI 1.07-10.9) respectively. The sensitivity of VIA to detect a p16INK4a/Ki-67 positive transforming infection was 13% (95%CI 2-38). Conclusions: Primary HPV testing appears feasible and should be considered as a primary screening test also in LMICs. The poor sensitivity of VIA renders it unsuitable as a triage test for HPV positive women. The utility of p16INK4a/Ki-67 dual stain cytology as a triage test for HPV positive women in LMICs should be further studied.

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Novel Concepts in Cervical Cancer Screening. A Comparison of VIA, HPV DNA Test and p16ink4a/Ki-67 Dual-Stain Cytology in Western Kenya.

10.21203/rs.3.rs-39673/v1 ◽

2020 ◽

Author(s):

Elkanah Omenge Orang’o ◽

Edwin Were ◽

Oliver Rode ◽

Kapten Muthoka ◽

Michael Byczkowski ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Screening Program ◽

Hpv Infection ◽

High Morbidity ◽

Ki 67 ◽

Dna Test ◽

Hpv Dna ◽

Triage Test

Abstract Background: Screening of unvaccinated women remains essential to mitigate the high morbidity/mortality of cervical cancer. Here, we compared visual inspection with acetic acid (VIA), recommended by WHO as the most cost-effective screening approach in LMICs, with HPV-based screening, and usage of p16INK4a/Ki-67 dual stain cytology.Methods: We prospectively enrolled women participating in a VIA-based cervical cancer screening program in two peri-urban health centers of Kenya. Consenting women had a VIA examination preceded by collection of a liquid-based cytology sample from the cervix stored in PreservCyt medium (Hologic®). Analysis of all samples included a hrHPV DNA test and evaluation of a p16 INK4a /Ki-67 (CINtecPLUS®) dual-stained slide that was prepared using the ThinPrep® 2000 Processor and evaluated by a pathologist trained in the methodology.Results: In 701 of a total of 800 women aged 18-64 years, all three investigations were performed and data could be analyzed. The HPV, VIA and dual-stain cytology positivity were 33%, 7%, and 2% respectively. The HPV positivity rate of VIA positive cases was 32%. The five most common HPV types were HPV16, 52, 68, 58 and 35. The OR among HIV infected women of an HPV infection, VIA positivity and positive dual stain cytology were 2.6 (95%CI 1.5-4.3), 1.9 (95%CI 0.89-4.4) and 3.4 (95%CI 1.07-10.9) respectively. The sensitivity of VIA to detect a p16INK4a/Ki-67 positive transforming infection was 13% (95%CI 2-38). Conclusions: Primary HPV testing appears feasible and should be considered as a primary screening test also in LMICs. The poor sensitivity of VIA renders it unsuitable as a triage test for HPV positive women. The utility of p16ink4a/Ki-67 dual-stain cytology as a triage test for HPV positive women in LMICs should be further studied.

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Role of Ancillary Techniques in Gynecologic Cytopathology Specimens

Acta Cytologica ◽

10.1159/000496569 ◽

2019 ◽

Vol 64 (1-2) ◽

pp. 63-70

Author(s):

Andrea D. Olivas ◽

Julieta E. Barroeta ◽

Ricardo R. Lastra

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Cancer Screening ◽

High Risk ◽

Cervical Cancer Screening ◽

Hpv Testing ◽

Invasive Procedures ◽

Ki 67 ◽

Dual Staining

The association between high-risk genotypes of human papillomavirus (hr-HPV) and cervical cancer is well established. As hr-HPV testing is rapidly becoming a part of routine cervical cancer screening, either in conjunction with cytology or as primary testing, the management of hr-HPV-positive women has to be tailored in a way that increases the detection of cervical abnormalities while decreasing unnecessary colposcopic biopsies or other invasive procedures. In this review, we discuss the overall utility and strategies of hr-HPV testing, as well as the advantages and limitations of potential triage strategies for hr-HPV-positive women, including HPV genotyping, p16/Ki-67 dual staining, and methylation assays.

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Genotypes distribution of human papillomavirus in cervical samples of Ecuadorian women

Revista Brasileira de Epidemiologia ◽

10.1590/1980-5497201600010014 ◽

2016 ◽

Vol 19 (1) ◽

pp. 160-166 ◽

Cited By ~ 8

Author(s):

Gustavo David García Muentes ◽

Lindsay Karen García Rodríguez ◽

Ramiro Israel Burgos Galarraga ◽

Franklin Almeida Carpio ◽

Juan Carlos Ruiz Cabezas

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Gynecological Cancer ◽

Hpv Infection ◽

Multiple Infections ◽

Hpv 16 ◽

Hpv Dna ◽

Hpv 18

ABSTRACT: Introduction: Human papillomavirus (HPV) is considered a necessary causative agent for developing oropharyngeal, anal and cervical cancer. Among women in Ecuadorian population, cervical cancer ranks as the second most common gynecological cancer. Not many studies about HPV burden have been published in Ecuador, and genotypes distribution has not been established yet. The little data available suggest the presence of other genotypes different than 16 and 18. Objectives: In the present study, we attempt to estimate the prevalence of HPV 16, HPV 18 and other 35 genotypes among Ecuadorian women undergoing cervical cancer screening. The overall prevalence of HPV infection was also estimated. Methods: Routine cervical samples were analyzed using Linear Array(r) HPV Genotyping test (Roche). Results: A total of 1,581 cervical samples obtained from Ecuadorian women undergoing cervical cancer screening were included in this study. HPV DNA was detected in 689 cervical samples (43.58%). Of these samples, 604 (38.20%) were positive for a single HPV genotype, while another 85 (5.37%) samples were positive for multiple HPV types. Genotype 16 (5.50%) resulted in the most frequently detected type in both single and multiple infections. HPV 33 (4.55%) and HPV 11 (3.80%) occupied the second and the third place in frequency among all detected genotypes. Conclusions: Viral genotypes different from HPV 16 and HPV 18 are frequently detected among Ecuadorian women. The overall prevalence of HPV resulted higher than the one reported in other South American countries with a greater burden in the second and third decades of life.

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P824 Accuracy of cervical cancer screening using a self-collected vial for HPV DNA testing among adult women in sub-saharan africa

10.1136/sextrans-2019-sti.869 ◽

2019 ◽

Author(s):

Zita Aleyo Nodjikouambaye ◽

Damtheou Sadjoli ◽

Ralph Sydney Mboumba Bouassa ◽

Hélène Péré ◽

David Veyer ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Sub Saharan Africa ◽

Adult Women ◽

Dna Testing ◽

Hpv Dna ◽

Hpv Dna Testing ◽

Sub Saharan

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Oncogenic HPV-DNA testing alone as cervical cancer screening in high-risk population of Southern Mexico

Journal of Clinical Oncology ◽

10.1200/jco.2008.26.15_suppl.16519 ◽

2008 ◽

Vol 26 (15_suppl) ◽

pp. 16519-16519

Author(s):

F. Gutierrez-Delgado ◽

J. E. Enriquez-Freire ◽

H. Leon-Velasco ◽

J. A. Manzur-Perez ◽

A. Baron-Rojas ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

High Risk ◽

Cervical Cancer Screening ◽

High Risk Population ◽

Dna Testing ◽

Southern Mexico ◽

Hpv Dna ◽

Hpv Dna Testing ◽

Oncogenic Hpv

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Concordance in HPV Detection Between Self-Collected and Health Provider–Collected Cervicovaginal Samples Using careHPV in Tanzanian Women

JCO Global Oncology ◽

10.1200/go.20.00598 ◽

2021 ◽

pp. 985-991

Author(s):

Johnson J. Katanga ◽

Vibeke Rasch ◽

Rachel Manongi ◽

Andrea B. Pembe ◽

Julius D. Mwaiselage ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

High Risk ◽

Cervical Cancer Screening ◽

Screening Method ◽

Health Provider ◽

Limited Information ◽

Sample Collection ◽

Hpv Dna ◽

High Risk Hpv

PURPOSE Cervical cancer screening is one of the strategies to prevent the disease among women at risk. Human papillomavirus (HPV) DNA testing is increasingly used as the cervical cancer screening method because of its high sensitivity. Self-collection of cervical specimens has the potential to improve participation. However, there is only limited information on comparison between self-collected and provider-collected samples with regard to detection of high-risk HPV using the careHPV method. The study aimed to compare HPV detection by careHPV in self-collected and provider-collected cervical samples and to assess the acceptability of self-collection techniques. MATERIAL AND METHODS Women attending cervical cancer screening clinics at Ocean Road Cancer Institute, Kilimanjaro Christian Medical Centre or Mawenzi Hospital in Tanzania were included in the study. They underwent a face-to-face interview, HIV testing, and collected a self-sample using Evalyn Brush. Subsequently, they had a cervical sample taken by a health provider. Both samples were tested for high-risk HPV DNA using careHPV. RESULTS Overall, 464 women participated in the study. The high-risk HPV prevalence was 19.0% (95% CI, 15.6 to 22.9) in the health provider samples, but lower (13.8%; 95% CI, 10.9 to 17.3) in the self-collected samples. There was a good overall agreement 90.5% (95% CI, 87.5 to 93.0) and concordance (κ = 0.66; 95% CI, 0.56 to 0.75) between the two sets of samples. Sensitivity and specificity were 61.4% (95% CI, 50.4 to 71.6) and 97.3% (95% CI, 95.2 to 98.7), respectively, varying with age. Most women preferred self-collection (79.8%). CONCLUSION Overall, self-sampling seems to be a reliable alternative to health-provider collection and is acceptable to the majority of women. However, instructions on proper procedures for sample collection to the women are important.

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