Comparison of a novel HPV test with the Hybrid Capture II (hcII) and a reference PCR method shows high specificity and positive predictive value for 13 high-risk human papillomavirus infections

Objective To compare, in a primary human papillomavirus screening setting, two different validated human papillomavirus tests, considering their analytical and clinical screening performances. Methods In Tuscany, a human papillomavirus screening program was implemented in 2013. Hybrid capture 2 (Qiagen) was used for testing until May 2016, when it was replaced by the cobas® 4800 human papillomavirus test (Cobas; Roche). We evaluated the performance of Hybrid capture 2 and Cobas on: the same screening population in two different periods (before and after changing to Cobas); the same Hybrid capture 2-positive consecutive samples. Discordant samples (Hybrid capture 2-positive/Cobas negative) were typed on the L1 gene (reverse line blot, AB Analitica) and E6/E7 genes (BD Onclarity assay). Results In the considered time period ( n = 37,775), human papillomavirus positivity was 9.8% and 7.4%, respectively, for Hybrid capture 2 and Cobas ( p < 0.0001). At immediate colposcopy, the cervical intraepithelial neoplasia, grade 2 positive predictive value was, respectively, 23.8% and 34% ( p < 0.001). At one-year recall, human papillomavirus persistence was, respectively, 40.6% and 62.2% ( p < 0.0001). Of Hybrid capture 2-positive re-tested samples ( n = 620), 32.4% were Cobas negative. Of discordant samples typed on L1, 7% were positive for the 12 high-risk human papillomavirus. Of the samples found to be negative for the 12 high-risk human papillomavirus types on L1, 14.5% were positive on E6/E7 typing. Among the discordant samples, the only two cervical intraepithelial neoplasia (CIN) grade 3 lesions were non-high-risk human papillomavirus positive on both L1 and E6/E7 typing. Conclusion At baseline, Hybrid capture 2 showed greater human papillomavirus positivity and a lower CIN2+ positive predictive value than Cobas, which was more specific than Hybrid capture 2 in detection of high-risk human papillomavirus: 80% of discordant samples were confirmed as high-risk human papillomavirus negative. This higher analytical specificity determined the non-identification of two CIN3 lesions.

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Atypical Squamous Cells, Cannot Exclude High-Grade Squamous Intraepithelial Lesion: Concordance, High-Risk Human Papillomavirus status, and Positive Predictive Value

Journal of the American Society of Cytopathology ◽

10.1016/j.jasc.2015.09.060 ◽

2015 ◽

Vol 4 (6) ◽

pp. S25-S26

Author(s):

Mansooreh Eghtesadghalati ◽

Ruth Dietrich ◽

Erin Tank ◽

Michelle Kanter ◽

John Groth ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Positive Predictive Value ◽

Predictive Value ◽

High Grade ◽

Squamous Intraepithelial Lesion ◽

Squamous Cells ◽

Intraepithelial Lesion

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Assessment of a new low-cost, PCR-based strategy for high-risk human papillomavirus DNA detection for cervical cancer prevention

BMC Infectious Diseases ◽

10.1186/s12879-019-4527-9 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Pedro Surriabre ◽

Andrea Torrico ◽

Tania Vargas ◽

Fuantina Ugarte ◽

Patricia Rodriguez ◽

...

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

High Risk ◽

Low Income ◽

Low Cost ◽

Low Income Countries ◽

Hybrid Capture ◽

Hpv Test ◽

Novel Strategy ◽

Level Of Agreement

Abstract Background HPV test implementation as a primary screening tool has the potential to decrease cervical cancer incidence as shown by several studies around the world. However, in many low-resource settings, the HPV test introduction has been backed down mainly due to its price. In this study, we present a novel low-cost strategy involving simple devices and techniques for high-risk human papillomavirus (HR-HPV) detection. The analytical performance to detect HR-HPV infections of this novel strategy was assessed by comparing it with the Hybrid Capture 2 system (HC2), which is used as gold standard. Methods Paired-cervical samples were collected from 541 women assisting to gynecological services in an outpatient clinic. One sample was transported in the Hybrid Capture Standard Transport Medium for HR-HPV detection by the HC2. The second sample was transported on glass slide for detection by PCR-based techniques (GP-EIA, BSGP-EIA and pU 1 M-L/2R). Results The level of agreement between the PCR-based techniques and HC2 system was determined with the Cohen’s kappa value. The kappa values between HC2 and GP-EIA, BSGP-EIA and pU 1 M-L/2R were 0.71 (CI 95% 0.63–0.78), 0.78 (CI 95% 0.71–0.84) and 0.63 (CI 95% 0.55–0.72), respectively. However, when the results from both BSGP-EIA and pU 1 M-L/2R were combined, the level of agreement with HC2 was increased to 0.82 (CI 95% 0.76–0.88), reflecting a very good agreement between the two HR-HPV detection strategies. Furthermore, the sensitivity of both techniques combined was also increased compared to the BSGP-EIA (88.7% vs 77.4%) and the pU (88.7 vs 60.9%) without penalizing the specificity obtained with the BSGP-EIA (95.1% vs 96.9%) and the pU (95.1% vs 96.5%). Conclusions This novel strategy, combining two PCR-based techniques for HR-HPV detection, could be useful for cervical cancer screening in self-collected samples in low-income countries.

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Evaluation of a Novel Single-Tube Method for Extended Genotyping of Human Papillomavirus

Journal of Clinical Microbiology ◽

10.1128/jcm.01687-17 ◽

2017 ◽

Vol 56 (3) ◽

Cited By ~ 2

Author(s):

R. Bhatia ◽

I. Serrano ◽

H. Wennington ◽

C. Graham ◽

H. Cubie ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Predictive Value ◽

Clinical Performance ◽

Specific Level ◽

Hpv Genotyping ◽

Hpv Test ◽

Hybrid Capture 2 ◽

Sensitivity Specificity ◽

High Risk Hpv

ABSTRACT The use of high-risk human papillomavirus (HPV) testing for surveillance and clinical applications is increasing globally, and it is important that tests are evaluated to ensure they are fit for this purpose. In this study, the performance of a new HPV genotyping test, the Papilloplex high-risk HPV (HR-HPV) test, was compared to two well-established genotyping tests. Preliminary clinical performance was also ascertained for the detection of CIN2+ in a disease-enriched retrospective cohort. A panel of 500 cervical liquid-based cytology samples with known clinical outcomes were tested by the Papilloplex HR-HPV test. Analytical concordance was compared to two assays: a Linear Array (LA) HPV genotyping test and an Optiplex HPV genotyping test. The initial clinical performance for the detection for CIN2+ samples was performed and compared to that of two clinically validated HPV tests: a RealTime High-Risk HPV test (RealTime) and a Hybrid Capture 2 HPV test (HC2). High agreement for HR-HPV was observed between the Papilloplex and LA and Optiplex HPV tests (97 and 95%, respectively), with kappa values for HPV16 and HPV18 being 0.90 and 0.81 compared to the LA and 0.70 and 0.82 compared to the Optiplex test. The sensitivity, specificity, positive predictive value, and negative predictive value of the Papilloplex test for the detection of CIN2+ were 92, 54, 33, and 96%, respectively, and very similar to the values observed with RealTime and HC2. The Papilloplex HR-HPV test demonstrated a analytical performance similar to those of the two HPV genotyping tests at the HR-HPV level and the type-specific level. The preliminary data on clinical performance look encouraging, although further longitudinal studies within screening populations are required to confirm these findings.

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A highly predictive signature of cognition and brain atrophy for progression to Alzheimer’s dementia

10.1101/352344 ◽

2018 ◽

Author(s):

Angela Tam ◽

Christian Dansereau ◽

Yasser Itturia-Medina ◽

Sebastian Urchs ◽

Pierre Orban ◽

...

Keyword(s):

Machine Learning ◽

Clinical Trials ◽

High Risk ◽

Positive Predictive Value ◽

Predictive Value ◽

High Specificity ◽

Alzheimer’S Dementia ◽

Learning Tools ◽

Operating Characteristics ◽

Alzheimer's Dementia

AbstractClinical trials in Alzheimer’s disease need to enroll patients whose cognition will decline over time, if left untreated, in order to demonstrate the efficacy of an intervention. Machine learning models used to screen for patients at risk of progression to dementia should therefore favor specificity (detecting only progressors) over sensitivity (detecting all progressors), especially when the prevalence of progressors is low. Here, we explore whether such high-risk patients can be identified using cognitive assessments and structural neuroimaging, by training machine learning tools in a high specificity regime. A multimodal signature of Alzheimer’s dementia was first extracted from ADNI1. We then validated the predictive value of this signature on ADNI1 patients with mild cognitive impairment (N=235). The signature was optimized to predict progression to dementia over three years with low sensitivity (55.1%) but high specificity (95.6%), resulting in only moderate accuracy (69.3%) but high positive predictive value (80.4%, adjusted for a “typical” 33% prevalence rate of true progressors). These results were replicated in ADNI2 (N=235), with 87.8% adjusted positive predictive value (96.7% specificity, 47.3% sensitivity, 85.1% accuracy). We found that cognitive measures alone could identify high-risk individuals, with structural measurements providing a slight improvement. The signature had comparable receiver operating characteristics to standard machine learning tools, yet a marked improvement in positive predictive value was achieved over the literature by selecting a high specificity operating point. The multimodal signature can be readily applied for the enrichment of clinical trials.

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The Role of Self-Collection by Vaginal Lavage for the Detection of HPV and High-Grade Intraepithelial Neoplasia

Acta Cytologica ◽

10.1159/000477331 ◽

2017 ◽

Vol 61 (6) ◽

pp. 425-433 ◽

Cited By ~ 3

Author(s):

Larissa de Melo Kuil ◽

Adriana Tarla Lorenzi ◽

Maíra Degiovani Stein ◽

Júlio César Possati Resende ◽

Márcio Antoniazzi ◽

...

Keyword(s):

High Risk ◽

Positive Predictive Value ◽

Predictive Value ◽

Pap Test ◽

Intraepithelial Neoplasia ◽

Cervical Cytology ◽

High Grade ◽

Vaginal Lavage ◽

Hpv Test ◽

High Risk Hpv

Objective: To compare the results of cervical cytology and high-risk HPV tests using samples obtained using two different collection modalities in a population of Brazilian women: self-collection (vaginal lavage) and cervical Pap testing. Methods: We enrolled 204 women who were aged 18-64 years and had previously obtained abnormal cervical cytology test results; 83.8% of them agreed to participate. The sample was divided into two aliquots: one for the cytological study and one for the molecular analysis of high-risk HPV. Results: Fifty-eight percent of the participants preferred to utilize self-collection as an alternative screening method. However, we noticed that the HPV positivity rate was significantly lower in self-collected samples when compared to those obtained using the conventional collection method (p = 0.035). The cytology tests of the samples obtained via self-collection were sensitive and had a positive predictive value and an area under the curve (AUC) that were significantly lower than those of the Pap test. However, the specificity and negative predictive value of these tests were similar. When compared with the HPV test, the self-collected samples demonstrated lower accuracy in predicting high-grade cervical intraepithelial neoplasia or worse, with a significantly lower sensitivity, positive predictive value, and AUC than the cervical Pap test samples. Conclusion: Self-collection by vaginal lavage is simple and well accepted by women. Due to its limitations, however, self-collection by lavage should be utilized with caution.

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The Prevalence of Human Papillomavirus–Positive Oropharyngeal Squamous Cell Carcinoma at One of the Largest Tertiary Care Centers in Sub-Saharan Africa

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2021-0021-oa ◽

2021 ◽

Author(s):

Gloria Dapaah ◽

Jos Hille ◽

William C. Faquin ◽

Judith Whittaker ◽

Corneli M. Dittrich ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Human Papillomavirus ◽

High Risk ◽

Positive Predictive Value ◽

Cell Carcinoma ◽

Squamous Cell ◽

Predictive Value ◽

Oropharyngeal Squamous Cell Carcinoma ◽

Sub Saharan Africa ◽

High Risk Hpv

Context.— Limited data exist on the prevalence of human papillomavirus (HPV)–positive oropharyngeal squamous cell carcinoma in sub-Saharan Africa. Objective.— To determine the prevalence of HPV-positive oropharyngeal squamous cell carcinoma at a large tertiary care center in South Africa. Design.— A total of 266 oropharyngeal squamous cell carcinomas diagnosed during an 11-year period (2007–2017) were selected for evaluation. Cases staining positive for p16 immunohistochemistry were evaluated for high-risk HPV using the BD Onclarity assay (BD Diagnostics, Sparks, Maryland). Results.— Of 266 oropharyngeal squamous cell carcinomas, 14% (n = 36) were positive for p16. Polymerase chain reaction for high-risk HPV performed on the p16-positive cases was negative in 23 cases and positive in 13 cases (13 of 266; 5%). p16 showed a positive predictive value of 36.1%. The HPV subtypes were HPV-16 (n = 10), HPV-18 (n = 1), HPV-52 (n = 1), and HPV-31 (n = 1). Human papillomavirus–positive cases occurred in 10 men and 3 women (mean age, 51 years) and arose from the tonsil (n = 10) or base of the tongue (n = 3). The HPV-positive cases were non-keratinizing (n = 10) or partially keratinizing (n = 1). Partially/nonkeratinizing cases revealed a modest improvement in p16 positive predictive value (11 of 21; 52.4%). Conclusions.— The presence of high-risk HPV in 5% of cases suggests that high-risk HPV is a minor etiologic agent in oropharyngeal squamous cell carcinoma in this region. Given its suboptimal positive predictive value, p16 is not a reliable marker for high-risk HPV infection in this region. When p16 is positive, HPV-specific testing is necessary. The identification of less common high-risk HPV types, HPV-52 and HPV-31, may influence current local vaccination strategies.

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