scholarly journals Feasibility study of a human papillomavirus E6 and E7 oncoprotein test for the diagnosis of cervical precancer and cancer

2018 ◽  
Vol 46 (3) ◽  
pp. 1033-1042 ◽  
Author(s):  
Jin-Jun Zhang ◽  
Xin-Chun Cao ◽  
Xiang-Yu Zheng ◽  
Hai-Ying Wang ◽  
Yong-Wei Li
Keyword(s):  
Human Papillomavirus ◽  
Intraepithelial Neoplasia ◽  
Clinical Value ◽  
Early Screening ◽  
Protein Assay ◽  
Dna Test ◽  
Hpv Dna ◽  
E7 Oncoprotein ◽  
Hpv E6 ◽  
E6 And E7

Objective To evaluate the clinical value of human papillomavirus (HPV) E6 and E7 oncoprotein (HPV E6/E7) detection in the early screening of cervical cancer. Methods This prospective study evaluated all patients with suspected cervical intraepithelial neoplasia (CIN) as identified by the presence of at least one positive indicator from a ThinPrep cytologic test (TCT) and/or a Hybrid Capture 2 (HC2) HPV DNA test. The levels of E6/E7 oncoproteins were determined using Western blot analysis. The diagnostic value of the HPV E6/E7 protein assay was compared with the clinical diagnosis from TCT, HC2 and the gold standard of cervical biopsy histology. Results A total of 450 patients were enrolled in the study and based on histological findings, 102 patients were diagnosed with CIN1 (22.7%), 241 with CIN2 (53.6%), 96 with CIN3 (21.3%) and 11 with squamous cell carcinoma (2.4%). For a diagnosis of CIN2+, although the sensitivity of the HPV E6/E7 assay was lower than HC2 (65.5% versus 96.6%, respectively), the specificity was higher (38.2% versus 5.9%, respectively). The sensitivity of the HPV E6/E7 assay was higher than TCT (65.5% versus 36.2%, respectively). Conclusion Measuring HPV E6/E7 oncoprotein levels is a potential new biomarker for HPV type 16.

scholarly journals Sensitivity, Specificity, and Clinical Value of Human Papillomavirus (HPV) E6/E7 mRNA Assay as a Triage Test for Cervical Cytology and HPV DNA Test

2011 ◽  
Vol 49 (7) ◽  
pp. 2643-2650 ◽  
Author(s):  
Maria Benevolo ◽  
Amina Vocaturo ◽  
Donatella Caraceni ◽  
Deborah French ◽  
Sandra Rosini ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Cervical Cytology ◽  
Clinical Value ◽  
Dna Test ◽  
Hpv Dna ◽  
Hpv E6 ◽  
Sensitivity Specificity ◽  
Triage Test ◽  
Hpv Dna Test

scholarly journals Validation of a Human Papillomavirus (HPV) DNA Cervical Screening Test That Provides Expanded HPV Typing

2018 ◽  
Vol 56 (5) ◽  
Author(s):  
Maria Demarco ◽  
Olivia Carter-Pokras ◽  
Noorie Hyun ◽  
Philip E. Castle ◽  
Xin He ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Excellent Agreement ◽  
Cervical Screening ◽  
Weighted Kappa ◽  
Clinical Value ◽  
Becton Dickinson ◽  
Major Question ◽  
Dna Test ◽  
Hpv Dna ◽  
Hpv Test

ABSTRACT As cervical cancer screening shifts from cytology to human papillomavirus (HPV) testing, a major question is the clinical value of identifying individual HPV types. We aimed to validate Onclarity (Becton Dickinson Diagnostics, Sparks, MD), a nine-channel HPV test recently approved by the FDA, by assessing (i) the association of Onclarity types/channels with precancer/cancer; (ii) HPV type/channel agreement between the results of Onclarity and cobas (Roche Molecular Systems, Pleasanton, CA), another FDA-approved test; and (iii) Onclarity typing for all types/channels compared to typing results from a research assay (linear array [LA]; Roche). We compared Onclarity to histopathology, cobas, and LA. We tested a stratified random sample ( n = 9,701) of discarded routine clinical specimens that had tested positive by Hybrid Capture 2 (HC2; Qiagen, Germantown, MD). A subset had already been tested by cobas and LA ( n = 1,965). Cervical histopathology was ascertained from electronic health records. Hierarchical Onclarity channels showed a significant linear association with histological severity. Onclarity and cobas had excellent agreement on partial typing of HPV16, HPV18, and the other 12 types as a pool (sample-weighted kappa value of 0.83); cobas was slightly more sensitive for HPV18 and slightly less sensitive for the pooled high-risk types. Typing by Onclarity showed excellent agreement with types and groups of types identified by LA (kappa values from 0.80 for HPV39/68/35 to 0.97 for HPV16). Onclarity typing results corresponded well to histopathology and to an already validated HPV DNA test and could provide additional clinical typing if such discrimination is determined to be clinically desirable.

Intracellular Human Papillomavirus E6, E7 mRNA Quantification Predicts CIN 2+ in Cervical Biopsies Better Than Papanicolaou Screening for Women Regardless of Age

2012 ◽  
Vol 136 (8) ◽  
pp. 956-960 ◽  
Author(s):  
Deirdre Pierry ◽  
Gerald Weiss ◽  
Benjamin Lack ◽  
Victor Chen ◽  
Judy Fusco
Keyword(s):  
Human Papillomavirus ◽  
Poor Performance ◽  
Intraepithelial Neoplasia ◽  
Low Grade ◽  
Abnormal Cytology ◽  
Mrna Quantification ◽  
Hpv Dna ◽  
Hpv E6 ◽  
Screening Population ◽  
Intraepithelial Lesion

Context.—Cervical cancer screening in women younger than 30 years relies on cervical cytology because of the poor performance of human papillomavirus (HPV) DNA testing in this age group. Objectives.—To determine the performance of in-cell HPV E6, E7 mRNA quantification (HPV OncoTect) for the detection of high-grade cervical intraepithelial neoplasia in women younger than 30 years. Design.—We analyzed 3133 cytology specimens from a screening population of women aged 19–75 years investigate HPV OncoTect as a triage/secondary screening test for atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cytology in women younger than 30 years. Test results were compared to histology in 246 cases. Results.—The sensitivity of E6, E7 mRNA was 89% for CIN 2+ and 100% for CIN 3+ lesions in women 30 years and older. In women younger than 30 years, the sensitivity of E6, E7 mRNA for CIN 2+ lesions was 88% for CIN 2+ and 92% for CIN 3+ lesions. Abnormal cytology (≥ASCUS) exhibited a sensitivity of 89% for CIN 2+ and 100% for CIN 3+ in women 30 years and older and 96% sensitivity for CIN 2+ and 93% sensitivity for CIN 3+ in women younger than 30. The specificity of E6, E7 mRNA was >80% for CIN 2+ and CIN 3+ in both groups of women compared to a specificity of abnormal cytology of <10% for CIN 2+ and CIN 3+ in both groups. Conclusions.—HPV OncoTect demonstrates a performance that would be effective for ASCUS/LSIL triage in women including those younger than 30 years.

scholarly journals Identification of High-Risk Human Papillomavirus DNA, p16 and E6/E7 Oncoproteins in Laryngeal and Hypopharyngeal Squamous Cell Carcinomas

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1008
Author(s):  
Andrejs Lifsics ◽  
Valerija Groma ◽  
Maksims Cistjakovs ◽  
Sandra Skuja ◽  
Renars Deksnis ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Squamous Cell ◽  
Surrogate Marker ◽  
Hpv Infection ◽  
Hpv16 E6 ◽  
Hpv Dna ◽  
Molecular Virology ◽  
Hpv E6 ◽  
E6 And E7

Human papillomavirus (HPV) was proven to play a significant role in cancer development in the oropharynx. However, its role in the development of laryngeal (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC) remains to be clarified. High-risk HPV (HR-HPV) viral proteins E6 and E7 are considered to be pertinent to HPV-related carcinogenesis. Hence, our aim was to estimate LSCC and HPSCC for HR-HPV DNA, p16, and E6/E7 oncoprotein status by using molecular virology and immunohistochemistry methods. The prevalence of HPV16 infection was 22/41 (53.7%) and 20/31 (64.5%) for LSCC and HPSCC, accordingly. The majority of HPV16+ tumor samples were stage III or IV. In most samples, the presence of either HPV16 E6 or HPV16 E7 viral protein in dysplastic or tumor cells was confirmed using immunohistochemistry. Our results suggest a high prevalence of HPV16 as a primary HR-HPV type in LSCC and HPSCC. The lack of HPV E6/E7 oncoproteins in some tumor samples may suggest either the absence of viral integration or the presence of other mechanisms of tumorigenesis. The utilization of p16 IHC as a surrogate marker of HR-HPV infection is impractical in LSCC and HPSCC.

scholarly journals Comparison of Onclarity Human Papillomavirus (HPV) Assay with Hybrid Capture II HPV DNA Assay for Detection of Cervical Intraepithelial Neoplasia Grade 2 and 3 Lesions

2015 ◽  
Vol 53 (7) ◽  
pp. 2109-2114 ◽  
Author(s):  
F. Bottari ◽  
M. Sideri ◽  
C. Gulmini ◽  
S. Igidbashian ◽  
A. Tricca ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Clinical Performance ◽  
Absolute Risk ◽  
Intraepithelial Neoplasia ◽  
Cervical Lesions ◽  
Cervical Intraepithelial Neoplasia Grade ◽  
Hybrid Capture ◽  
Dna Test ◽  
Hpv Dna

Analytical and clinical performance validation is essential before introduction of a new human papillomavirus (HPV) assay into clinical practice. This study compares the new BD Onclarity HPV assay, which detects E6/E7 DNA from 14 high-risk HPV types, to the Hybrid Capture II (HC2) HPV DNA test, to concurrent cytology and histology results, in order to evaluate its performance in detecting high-grade cervical lesions. A population of 567 women, including 325 with ≥ASCUS (where ASCUS stands for atypical cells of undetermined significance) and any HC2 result and 242 with both negative cytology and negative HC2 results, were prospectively enrolled for the study. The overall agreement between Onclarity and HC2 was 94.6% (95% confidence intervals [CI], 92.3% to 96.2%). In this population with a high prevalence of disease, the relative sensitivities (versus adjudicated cervical intraepithelial neoplasia grades 2 and 3 [CIN2+] histology endpoints) of the Onclarity and HC2 tests were 95.2% (95% CI, 90.7% to 97.5%) and 96.9% (95% CI, 92.9% to 98.7%), respectively, and the relative specificities were 50.3% (95% CI, 43.2% to 57.4%) for BD and 40.8% (95% CI, 33.9%, 48.1%) for HC2. These results indicate that the BD Onclarity HPV assay has sensitivity comparable to that of the HC2 assay, with a trend to an increased specificity. Moreover, as Onclarity gives the chance to discriminate between the different genotypes, we calculated the genotype prevalence and the absolute risk of CIN2+: HPV 16 was the most prevalent genotype (19.8%) with an absolute risk of CIN2+ of 77.1%.

scholarly journals Triage of human papillomavirus infected women by methylation analysis in first-void urine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Severien Van Keer ◽  
Annina P. van Splunter ◽  
Jade Pattyn ◽  
Annemie De Smet ◽  
Sereina A. Herzog ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Host Cell ◽  
Intraepithelial Neoplasia ◽  
Underlying Disease ◽  
Hpv Infection ◽  
Molecular Testing ◽  
High Grade ◽  
Methylation Analysis ◽  
Hpv Dna ◽  
Screening Attendance

AbstractHost cell DNA methylation analysis in urine provides promising triage markers for women diagnosed with a high-risk (HR) human papillomavirus (HPV) infection. In this study, we have investigated a panel of six host cell methylation markers (GHSR, SST, ZIC1, ASCL1, LHX8, ST6GALNAC5) in cervicovaginal secretions collected within the first part of the urine void (FVU) from a referral population. Cytology, histology, and HPV DNA genotyping results on paired FVU and cervical samples were available. Urinary median methylation levels from HR-HPV (n = 93) positive women were found to increase for all markers with severity of underlying disease. Significantly elevated levels were observed for GHSR and LHX8 in relation to high-grade cervical intraepithelial neoplasia (CIN2 +; n = 33), with area under de curve values of 0.80 (95% Confidence Interval (CI) 0.59–0.92) and 0.76 (95% CI 0.58–0.89), respectively. These findings are the first to support the assertion that methylation analysis of host cell genes is feasible in FVU and holds promise as molecular, triage strategy to discern low- from high-grade cervical disease in HR-HPV positive women. Molecular testing on FVU may serve to increase cervical cancer screening attendance in hard-to-reach populations whilst reducing loss to follow-up and await further optimization and validation studies.

scholarly journals T-Cell Response to Human Papillomavirus Type 58 L1, E6, and E7 Peptides in Women with Cleared Infection, Cervical Intraepithelial Neoplasia, or Invasive Cancer

2010 ◽  
Vol 17 (9) ◽  
pp. 1315-1321 ◽  
Author(s):  
Paul K. S. Chan ◽  
Shih-Jen Liu ◽  
T. H. Cheung ◽  
Winnie Yeo ◽  
S. M. Ngai ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Amino Acid ◽  
T Cell ◽  
Cell Response ◽  
Positive Response ◽  
Intraepithelial Neoplasia ◽  
Amino Acid Position ◽  
T Cell Response ◽  
Ifn Γ ◽  
E6 And E7

ABSTRACT Human papillomavirus type 58 (HPV-58) exists in a relatively high prevalence in certain parts of the world, including East Asia. This study examined the T-cell response to HPV-58 L1, E6, and E7 peptides among women with cleared infection, cervical intraepithelial neoplasia grade 2 (CIN2) or CIN3, or invasive cervical cancer (ICC). Peptides found to be reactive in the in vitro peptide binding assay or mouse-stimulating study were tested with a gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay to detect peptide-specific responses from the peripheral blood mononuclear cells (PBMC) collected from 91 HPV-58-infected women (32 with cleared infection, 16 CIN2, 15 CIN3, and 28 ICC). Four HLA-A11-restricted HPV-58 L1 peptides, located at amino acid positions 296 to 304, 327 to 335, 101 to 109, and 469 to 477, showed positive IFN-γ ELISPOT results and were mainly from women with cleared infection. Two HLA-A11-restricted E6 peptides (amino acid positions 64 to 72 and 94 to 102) and three HLA-A11-restricted E7 peptides (amino acid positions 78 to 86, 74 to 82, and 88 to 96) showed a positive response. A response to E6 and E7 peptides was mainly observed from subjects with CIN2 or above. One HLA-A2-restricted E6 peptide, located at amino acid position 99 to 107, elicited a positive response in two CIN2 subjects. One HLA-A24-restricted L1 peptide, located at amino acid position 468 to 476, also elicited a positive response in two CIN2 subjects. In summary, this study has identified a few immunogenic epitopes for HPV-58 E6 and E7 proteins. It is worthwhile to further investigate whether responses to these epitopes have a role in clearing an established cervical lesion.

High-Risk Human Papillomavirus Affects Prognosis in Patients With Surgically Treated Oropharyngeal Squamous Cell Carcinoma

2006 ◽  
Vol 24 (36) ◽  
pp. 5630-5636 ◽  
Author(s):  
Lisa Licitra ◽  
Federica Perrone ◽  
Paolo Bossi ◽  
Simona Suardi ◽  
Luigi Mariani ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Oropharyngeal Cancer ◽  
Clinical Results ◽  
Hpv Dna ◽  
Additional Information ◽  
Second Tumors ◽  
E6 And E7 ◽  
Second Tumor ◽  
P16 Expression

Purpose Human papillomavirus (HPV) DNA tumors actively integrating the E6 and E7 oncogenes have a distinct biologic behavior resulting in a more favorable prognosis. To which extent the viral integration by itself, and/or the associated wild-type (wt) TP53 status, and/or a functional p16 contribute to prognosis is unclear. Patients and Methods To clarify how the presence of high-risk (HR) -HPV, TP53, and p16INK4a status interact with clinical outcome, we considered a retrospective series of 90 consecutive oropharyngeal cancer patients treated primarily with surgery. Results Seventeen (19%) patients showed integrated HPV 16 DNA (HPV positive), wt TP53 in all but two patients, normal p16INK4a in 15 assessable patients, and p16 expression in all 17 patients. Thirty-five patients (39%), two of whom were HPV positive, harbored TP53 mutations. p16INK4a deletion and p16 null immunophenotype occurred in 28 and 58 patients, respectively, and was similarly distributed in both patients with mutated TP53 (48% and 82%, respectively) and in patients with wt TP53 (46% and 77%, respectively). Statistical analysis showed that HPV-positive status significantly affects all investigated end points: overall survival (P = .0018), incidence of tumor relapse (P = .0371), and second tumor (P = .0152), whereas TP53 and p16INK4a status and p16 expression were not prognostic by themselves. Conclusion Our molecular and clinical results are in agreement with previous findings but provide additional information into the biologic mechanisms involved in HR-HPV oropharyngeal cancer in comparison to HPV-negative tumors. According to the reduced risk of relapse and second tumors associated with HR-HPV positivity of oropharyngeal cancer, the therapeutic strategy and follow-up procedures should be reviewed.

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