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

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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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

Acta Cytologica ◽

10.1159/000487504 ◽

2018 ◽

Vol 62 (2) ◽

pp. 104-114 ◽

Cited By ~ 2

Author(s):

Karla Calaça Kabbach Prigenzi ◽

Thaís Heinke ◽

Rafael Calil Salim ◽

Gustavo Rubino de Azevedo Focchi

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

High Risk ◽

Cervical Cancer Screening ◽

Hpv Infection ◽

Design Sensitivity ◽

Adult Women ◽

Ki 67 ◽

Predictive Values ◽

Hpv Dna

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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Trichomonas vaginalis as a risk factor for human papillomavirus: a study with women undergoing cervical cancer screening in a northeast region of Brazil

BMC Women s Health ◽

10.1186/s12905-021-01320-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ilka Kassandra Pereira Belfort ◽

Ana Paula Almeida Cunha ◽

Francisco Pedro Belfort Mendes ◽

Leonardo Victor Galvão-Moreira ◽

Renata Gaspar Lemos ◽

...

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Trichomonas Vaginalis ◽

Screening Program ◽

Hpv Infection ◽

Adverse Outcomes ◽

Behavioral Risk ◽

Hpv Dna

Abstract Background Human papillomavirus (HPV) and Trichomonas vaginalis (TV) infections are the most common sexually transmitted infections (STIs) globally. The latter has contributed to a variety of adverse outcomes for both sexes. Moreover, in Brazil, epidemiological studies on patients with STIs are limited. Therefore, this study aimed to determine the prevalence of TV and its association with HPV in women undergoing cervical cancer screening. Methods Women with a normal cervix were recruited from a community-based cervical cancer screening program. Gynecological examinations were conducted, and questionnaires were provided. Vaginal canal and uterine cervix samples were collected for cytological examinations (reported using the 2001 Bethesda System) and tested for the presence of TV and HPV DNA. Results In total, 562 women who attended public primary healthcare were included in the study. The T. vaginalis was present in 19.0% (107) and HPV DNA was present in 46.8% (263) of women. Among the women of TV 73.8% (79) had a co-infection with HPV (p = 0.001). Conclusions We concluded that a TV infection is associated with an HPV infection of the cervix as well as with the cervical cytological abnormalities. Further studies could reveal the mechanisms by which these two organisms interact at the cellular level, with control for shared behavioral risk factors.

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Trichomonas Vaginalis as A Risk Factor for Human Papillomavirus: A Study With Women Undergoing Cervical Cancer Screening

10.21203/rs.3.rs-68759/v1 ◽

2020 ◽

Author(s):

Ilka Kassandra Pereira Belfort ◽

Ana Paula Almeida Cunha ◽

Francisco Pedro Belfort Mendes ◽

Leonardo Victor Galvão-Moreira ◽

Renata Gaspar Lemos ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Trichomonas Vaginalis ◽

Screening Program ◽

Hpv Infection ◽

Adverse Outcomes ◽

Hpv Dna ◽

Health Council ◽

Increased Risk

Abstract BackgroundHuman papillomavirus (HPV) and Trichomonas vaginalis (TV) infections are the most common STIs. The latter has contributed to a variety of adverse outcomes for both sexes. Moreover, in Brazil, epidemiological studies on patients with STIs are limited. Therefore, this study aimed to determine the prevalence of TV and its association with HPV in women undergoing cervical cancer screening. MethodsWomen with a normal cervix were recruited from a community-based cervical cancer screening program. Gynecological examinations were conducted and questionnaires were provided. Vaginal canal and uterine cervix samples were collected and tested for the presence of TV and HPV DNA. ResultsThe overall prevalence of HPV DNA was 45.68%; among these, 27.1% had a co-infection with TV (p = 0.001). The presence of TV was associated with an increased risk of HPV (p = 0.0001) and previously identified cytological changes (p = 0.0001). ConclusionsWe concluded that a TV infection is associated with an HPV infection of the cervix as well as with the cervical cytological abnormalities. Further studies could reveal the mechanisms by which these two organisms interact at the cellular level, with control for shared behavioral risk factors. This research is in agreement with Resolution No. 466/2012 of the National Health Council and has the Research Ethics Committee of the Hospital Universitário Presidente Dutra, from Universidade Federal do Maranhão, under opinion number 76328917.5.0000.5086.

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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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Clinical Evaluation of Human Papillomavirus Screening With p16/Ki-67 Dual Stain Triage in a Large Organized Cervical Cancer Screening Program

JAMA Internal Medicine ◽

10.1001/jamainternmed.2019.0306 ◽

2019 ◽

Vol 179 (7) ◽

pp. 881 ◽

Cited By ~ 23

Author(s):

Nicolas Wentzensen ◽

Megan A. Clarke ◽

Renee Bremer ◽

Nancy Poitras ◽

Diane Tokugawa ◽

...

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Clinical Evaluation ◽

Screening Program ◽

Ki 67 ◽

Cancer Screening Program ◽

Cervical Cancer Screening Program

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The prevalence of hrHPV among the isolated community in the Highland of Bario, Sarawak, East Malaysia

10.21203/rs.2.17048/v1 ◽

2019 ◽

Author(s):

Abigail Rembui Jerip ◽

Mardiana Kipli ◽

Cheng-Siang Tan

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Outreach Program ◽

Low Resource Settings ◽

Dna Test ◽

Hpv Dna ◽

Low Resource ◽

Cervical Swab

Abstract Background Malaysia has introduced the free Pap smear as the primary cervical cancer screening program since the 1960s but has only achieved the national coverage of 22%. The coverage would be much lower in the rural communities especially in Sarawak where many villages are still inaccessible by road, and communities are living in low resource settings. In this study, we have evaluated Qiagen’s careHPV system as a point-of-care HPV diagnostic test together with the visualization using acetic acid (VIA) in the isolated community in the Highland of Bario which are predominantly from the Kelabit ethnicity. Methods Women attending the cervical cancer outreach program were recruited. Consent was obtained and a cervical swab was clinician-collected and screened for High-risk HPV DNA using the careHPV system. Cervical examination using VIA was offered to all women age <50-year. hrHPV positive women were recruited during their follow-up session and the second cervical swab was collected for HPV genotyping using consensus primer-nested PCR to elucidate the infecting HPV genotypes. Results Seventy-five women from the age of 27-83 (mean age 55) attended the cervical cancer screening clinic and 8% (n=6/75) of them were positive for hrHPV. Only 33 women were screened using VIA and 21.2% (n=7/33) were found to be positive. A majority of the women (58.6%) were above the age of 50-year and not recommended for VIA to be performed. Thus, it was not feasible to correlate the results obtained from the HPV DNA test and VIA. Only four hrHPV positive women returned for follow-up and genotyping revealed HPV52 in 2 of four women tested suggesting that HPV52 may be the predominant genotype in Bario. Conclusions The careHPV system is portable and can be used in low resource settings as long as reliable electricity is available. We found that careHPV DNA test is more objective compared to VIA and can be used to screen women outside the recommended eligible age. This is especially true for older women in the rural who have never had any form of cervical cancer screening before.

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