Cervista High-risk Human Papillomavirus Research Articles

Prevalence of high-risk human papilloma virus in liquid-based cervical samples from Turkish women with normal and abnormal cytology.

The aim of this study was to investigate the prevalence of human papilloma virus (HPV) infection from Turkish women with normal and abnormal cytology. Our study population consisted of 1252 women with normal and abnormal cytology. In our clinic, cervical cancer screening was performed by liquid-based cytology testing (ThinPrep Pap Test). Reflex high-risk (HR) HPV testing (Cervista HPV HR and HPV 16/18) was performed in cases with abnormal cytology (n = 330). HR HPV testing was performed to 922 cases with normal cytology. HR HPV was detected in 18.7% of negative for intraepithelial lesion or malignancy (NILM) samples, and in 79.7% of abnormal cytology cases. HPV types 16 and/or 18 were found in 18.6% and 35.3% of normal cytology cases and abnormal cytology cases, respectively. Of all 435 HR HPV-positive samples, HPV type 16 and/or 18 prevalence was significantly higher in cases with more severe cytological abnormalities. The HPV prevalence among Turkish women with normal and abnormal cytology identified in this study largely concurs with those in other studies throughout the world. HPV types 16 and/or 18 were detected significantly in normal cytology cases in our study. We also found that, as has been previously demonstrated, certain HPV genotypes (16/18) are associated with more severe pathologies. However, larger epidemiological studies in different regions of Turkey are needed to evaluate the accurate prevalence of HPV infection throughout the country.

Cervical cancer screening using the Cervista high-risk human papillomavirus test: opportunistic screening of a hospital-based population in Fujian province, China.

ObjectivesThe Cervista® high-risk human papillomavirus (HR-HPV) test was evaluated as a primary screening method for cervical cancer in women aged ≥21 years and was compared with different screening and triage combinations.Materials and methodsA nested case–control study within the Fujian provincial Cervical Lesion Screening Cohorts was used to evaluate the Cervista test as the primary cervical screening method in a hospital-based population. Strategy 1 primarily screened using a cytology screen with HR-HPV testing used for triage. Strategy 2 primarily screened using cytology and HR-HPV co-testing. Strategy 3 primarily screened using HR-HPV testing and triaged HPV-positive women based on cytology. Strategy 4 primarily screened using HR-HPV testing and referred A9 pool HPV-positive women to colposcopy directly, whereas non-A9 HPV-positive women were triaged using cytology.ResultsThere were 10,183 women included in this study; 16.49% (1677/10,183) were HR-HPV-positive, 9.52% had abnormal cytology, and 9907 women were normal during followup. A total of 276 women were diagnosed with cervical intraepithelial neoplasia 2 or worse (CIN2+), 197 with CIN3 or worse (CIN3+), and 70 with cervical cancer. Moreover, 10.15% (20/197) women who were CIN3+ were identified as cytology-negative, while 8.63% (17/197) were HR-HPV negative (P>0.05). The cumulative risk rate for HPV–/cytology– was 0.836 (95% CI, 0.424–1.648) in CIN3+ cases. Strategy 4 yielded the highest sensitivity for CIN2+ or CIN3+ and the lowest positive predictive value for CIN2+ or CIN3+ among the four screening strategies.ConclusionThe Cervista HR-HPV test can provide a reliable and sensitive clinical reference for the cervical cancer primary screen.

Role of high-risk human papillomavirus in the etiology of oral and oropharyngeal cancers in Thailand: A case-control study.

Background:Among developing countries, Thailand shows no increase in the incidence of human papillomavirus–driven oropharyngeal cancer. The causal role of human papillomavirus infection in this pathology has not been researched thoroughly.Methods:A hospital-based, case–control study was performed which included 104 patients with newly diagnosed oral and oropharyngeal squamous cell carcinomas and 104 individuals without cancer. The Cervista high-risk human papillomavirus and 16/18 assays were used to detect human papillomavirus. Odds ratios were used to assess the association between high-risk genotypes of human papillomavirus and the cancers.Results:High-risk human papillomavirus was detected in 4 of 52 (7.7%) oral cancer cases, 6 of 52 (11.5%) oropharyngeal cancer cases, and 1 of 104 (0.96%) control subjects. Of 104 cancer patients in the study, 83 were smokers. High-risk human papillomavirus was significantly associated with oropharyngeal cancer (odds ratio = 13.44, 95% confidence interval = 1.6–114.8) but was nonsignificantly associated with oral cancer (odds ratio = 8.58, 95% confidence interval = 0.9–78.9). However, after adjustment for smoking, high-risk human papillomavirus was determined to be nonsignificantly associated with oropharyngeal cancer (adjusted odds ratio = 5.83, 95% confidence interval = 0.8–43.5).Conclusion:Although low human papillomavirus prevalence was observed, the rate of high-risk human papillomavirus infection in the cancer group was still higher than that in the control group. Smoking may have an influence on the etiology of human papillomavirus–related cancers. However, the study is underpowered to clarify the role of human papillomavirus as the independent risk factor for oral and oropharyngeal cancers in the Thai population.

Comparison of the cervista HPV HR test and luminex XMAP technology for the diagnosis of cervical intraepithelial neoplasia

ObjectivesThis study was designed to compare the Cervista high risk (HR) human papillomavirus (HPV) test with Luminex XMAP technology for the detection of the relationship between HPV infection and cervical intraepithelial neoplasia. MethodsIn total, 3280 patients in a cervical specialty clinic were divided into two groups for either Cervista (1855 patients) or Luminex (1425 patients). Subsequent colposcopy examinations were performed in 1270 women with cytologic results showing ASCUS or higher level lesions. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were evaluated. ResultsThe positive rates of the Cervista and Luminex groups were 61.48% and 67.43%, respectively, and occurrence in those 30–40 years old was most common. The typing of HPV showed that A9 positive cases were the most prevalent genotype (33.53%), followed by A5/A6 (16.44%) and A7 (11.37%) in the Cervista group, and HPV-16 was the most prevalent genotype (25.81%), followed by HPV-18 (18.6%) and HPV-31 (8.6%) in the Luminex group. Moreover, the overall concordance rate was 96.26% (95% confidence interval, 93.51–99.00%) in the 187 women with cytologic results of ASCUS or higher. There were no significant differences in the positive rates of HPV between the Cervista and Luminex groups, and both had a high sensitivity and NPV. ConclusionsThe results showed a high good concordance between the two methods in diagnostic accuracy. Among the patients in the cervical specialty clinic, both the A9 group of HPV and HPV-16 showed the highest positive rate. Cervista and Luminex shared similar a clinical value in the detection of CIN2 or higher.

Clinical investigation of taking Cervista high-risk human Papilloma virus DNA test and cytological test in the same sample

Objective To explore the feasibility of taking Cervista high-risk human Papilloma virus DNA (Cervista HR HPVDNA) test and Thinprep cytologic test in the same sample, and to assess the availability and significance of Cervista HR HPVDNA in detecting HPV infection in people, also to study the correlation of Cervista A9 group with high grade cervical dysplasia and the value of HPV16/18 in diagnosing cervical dysplasia. Methods Totally 148 cases diagnosed in gynecology clinic during March to April, aging 20 to 65, cytological test ≥ASCUS (atypical squamous cells undetermined significance) were involved in the investigation group, and 153 cases with normal cytological test at the same time were involved in the control group. Cytological test and Cervista high-risk human Papilloma virus DNA test were implemented at the same time on two groups, cases with one of the test method tested abnormal were further biopsied under the colposcope if necessary. Results Cervista HR HPVDNA infection rate was 83.78% in the investigation group and 18.30% in the control group with statistic difference (P 0.05). We further founded that A9 group take the large proportion of Cervista HR HPVDNA infection, and co-infection by 2 or 3 genotypes tested in part grades and A9 group related with Pathology≥CINⅡ(P<0.05). The sensitivity, specificity, positive-predictive value and negative-predictive value of Cervista HR HPVDNA for detecting all cases of CINⅡ were 90.9%, 18.1%, 22.7%, and 88.2%, respectively. A portion (30.6%) of the Cervista HR HPVDNA positive cases showed HPV16/18 positive, while none showed in the Cervista HR HPVDNA negative cases. HPV16/18 infection rate in normal, CINⅠ, CINⅡ, CINⅢ, and Cervical carcinoma were 13.33%, 37.50%, 50.00%, 75%, and 100% with significant difference(Fisher exact Test P<0.05). Conclusions Cervista HR HPVDNA test was feasible as an Cervical carcinoma screening method. The method of combining Cervista HR HPVDNA test with cytological test in the same sample deserves promotion as its easy operating and definite effect. Key words: Biopsy; Uterine cervical neoplasms/DI; Papillomaviridae/ME

Clinical validation of the Cervista HPV HR test according to the international guidelines for human papillomavirus test requirements for cervical cancer screening.

This study demonstrates that both the clinical sensitivity and specificity of the Cervista HPV HR test for high-risk human papillomavirus (HPV) detection are not inferior to those of the Hybrid Capture 2 (HC2) test. The intra- and interlaboratory reproducibilities of Cervista were 92.0% (kappa, 0.83) and 90.4% (kappa, 0.80), respectively. The Cervista HPV HR test fulfills all the international HPV test requirements for cervical primary screening purposes.

Triage of Women With Negative Cytology and Positive High-Risk HPV

To determine a management strategy for women testing negative with cervical cytology and positive for high-risk human papillomavirus (HR-HPV). Using the data from the large population-based Shenzhen Cervical Cancer Screening Trials II and III (SHENCCAST II/III), we compared the risk for cervical intraepithelial neoplasia grade 3 or cancer (CIN 3+) in women with negative cytology but testing positive for HR-HPV DNA using Cervista HPV HR or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF), followed by secondary screening with type-specific Cervista HPV-16/18 or MALDI-TOF. The study aim was to seek the most sensitive and specific triage assay for referral for colposcopy. A total of 8,556 women had complete data. The proportion of women with negative cytology and positive HR-HPV by Cervista HR-HPV (5.30%, 453/8,556) was slightly lower than that of women with negative cytology and HR-HPV-positive tests by MALDI-TOF (5.82%, 499/8,556, p = .015). The proportion of women having negative cervical cytology and a positive HR-HPV by Cervista HR who have HPV-16 and/or -18 by Cervista HPV-16/18 (11.8%, 53/448) was less than that of women with a negative cervical cytology and positive HR-HPV by MALDI-TOF who have HPV-16 and/or -18 by MALDI-TOF (19.4%, 97/499, p = .001). The proportion of CIN 3+ within negative cervical cytology and positive HR-HPV that were HPV-16 and/or -18 for the Cervista 16/18 assay (61.5%, 8/13) was similar to that for the MALDI-TOF 16/18 assay (66.7%, 10/15, p = 0.8). In the cytology-negative HR-HPV-positive population, Cervista 16/18 as the HPV detection method would refer 11.8% of women for colposcopy and diagnose 61.5% of the CIN 3+, while MALDI-TOF16/18 would refer 19.4% and diagnose 66.7% of the CIN 3+. Cervista HPV-16/18 seems to be the superior triage test. However, in resource-limited settings, an assay that includes 16/18 genotyping in the primary result (rather than a second test) may be more cost efficient.

Effect of Preanalytical Processing of ThinPrep Specimens on Detection of High-Risk Human Papillomavirus by the Aptima HPV Assay

Two important preanalytical protocols performed on liquid-based cytological specimens, namely, automated cytology processing and glacial acetic acid (GAA) treatment, may occur prior to the arrival of specimens in a molecular diagnostics laboratory. Ninety-two ThinPrep vials previously positive for high-risk human papillomavirus (HPV) via the Cervista HPV HR test were preselected and alternated with 92 previously negative ThinPrep vials. The specimen set was processed in a consecutive fashion by an automated cytology processor without fastidious decontamination precautions. Carryover potential was subsequently assessed by performance of the Aptima HPV assay on aliquots from reprocessed ThinPrep vials. All previously negative ThinPrep vials yielded a negative result following routine automated cytology processing, despite close proximity to known-positive ThinPrep vials. In separate experiments, aliquots from 236 ThinPrep vials were forwarded for tandem analysis with and without GAA treatment. Data from GAA- and mock-treated specimens generated by Aptima HPV were compared to correlate data generated by Cervista. A 99.2% concordance of Aptima HPV results from GAA-treated and mock-treated specimens was noted. This result differed from the concordance result derived from Cervista (91.5%; P<0.0002). Of the initially positive Cervista results, 21.9% reverted to negative following GAA treatment; the correlate value was 2.7% for Aptima HPV (P=0.01). While deleterious effects of GAA treatment on genomic DNA were noted with Cervista (P=0.0015), GAA treatment had no significant effects on Aptima HPV specimen signal/cutoff ratios or amplification of internal control RNA (P≥0.07). The validity of an Aptima HPV result is independent of GAA treatment and routine automated cytology processing.

Cervista HPV assays for fine-needle aspiration specimens are a valid option for human papillomavirus testing in patients with oropharyngeal carcinoma.

The objectives of this study were to evaluate the validity of Cervista human papillomavirus (HPV) assays in head and neck fine-needle aspiration (FNA) specimens from patients with head and neck squamous carcinomas and to verify that the Cervista assay in FNA specimens is a valid option for determining HPV status in patients with oropharyngeal carcinomas. The authors retrospectively retrieved 64 head and neck FNA specimens from patients who had head and neck squamous carcinoma. The specimens were tested for HPV types 16 and 18 (HPV16/18) and for high-risk (HR) HPV DNA using the Cervista HPV16/18 and HPV HR assays, respectively. The results from those assays were compared with the results from polymerase chain reaction (PCR)-based HPV assays in the same tissues and with the results from HPV in situ hybridization assays/p16 immunostaining in the corresponding primary tumors. In total, 64 FNA specimens were analyzed. The Cervista HPV16/18 and/or HPV HR assays were positive in 48 of 64 specimens (75%), and there was a predominance of HPV16 (42 of 48 specimens; 88%). In the 49 specimens that had PCR-based test results, overall agreement with Cervista assay results was 96% (47 of 49 specimens; κ = 0.883). In the 49 specimens that had PCR-based HPV16/18 genotyping results, overall agreement with the Cervista HPV16/18 results was 94% (46 of 49 specimens; κ = 0.847). In the 36 primary carcinoma specimens that had valid HPV in situ hybridization/p16 immunostaining results, overall agreement with the Cervista assay results was 92% (33 of 36 specimens; κ = 0.679). Cervista HPV16/18 and Cervista HPV HR testing of head and neck FNA specimens is a valid option for determining HPV16/18 status in patients with oropharyngeal carcinoma.

Clinical Laboratory Experience with Cervista HPV HR as a Function of Cytological Classification: Comparison with Retrospective digene HC2 High-Risk HPV DNA Test Data

Kinney et al. [1] signaled caution over a purported increased rate of high-risk human papillomavirus (HPV) DNA detection from liquid-based cytology collections (ThinPrep; Cytyc Corporation, Marlborough, MA) with Cervista™ HPV HR (Cervista; Hologic, Madison, WI) when compared to the digene HC2 High-risk HPV DNA Test (HC2; Qiagen, Gaithersburg, MD).…

Clinical Performance Characteristics of the Cervista HPV HR Test Kit in Cervical Cancer Screening in China

A multicenter clinical trial was performed to evaluate and validate the performance of Cervista HPV HR test and to establish its effectiveness in identifying women at risk of having cervical intraepithelial neoplasia 2 (CIN 2) or higher grade (CIN 2+) in the Chinese population. Residual ThinPrep Pap Test samples from women who are negative for intraepithelial lesion or malignancy (NILM) and atypical squamous cells of undetermined significance (ASCUS) or higher grade cytology were tested for high-risk human papillomavirus (HPV). The HPV test results were compared with histology results to determine the clinical sensitivity, specificity, positive predictive value, and negative predictive value of Cervista HPV HR for CIN 2+. The analytical accuracy of Cervista HPV HR compared with consensus HPV L1 polymerase chain reaction (PCR)/sequencing was also determined. A total of 1,064 subjects were enrolled, including 544 with NILM cytology and 520 with ASCUS or higher grade cytology. Complete data sets including cytology, high-risk HPV test, colposcopy, and histology results for all subjects with ASCUS or higher grade were included in the analysis. The positive rate of Cervista HPV HR was 12.5% in patients with NILM and 69.04% in patients with ASCUS or higher grade. The overall percentage agreement between Cervista HPV HR and PCR with bidirectional sequencing was 86.26%, with positive percentage agreement and negative percentage agreement being 93.4% and 83.3%, respectively. In the overall population, the Cervista HPV HR positivity rate was 38.96% compared with 29.08% for PCR/sequencing. The clinical sensitivity and specificity for CIN 2+ of Cervista HPV HR were 98.50% and 68.21%, respectively. The negative and positive predictive values were 99.69% and 30.68%, respectively. The Cervista HPV HR test, performed on ThinPrep Pap Test samples, has the clinical performance characteristics required by China for use as part of routine cervical cancer screening.

Comparison of the Seeplex HPV4A ACE and the Cervista HPV assays for the detection of HPV in hybrid capture 2 positive media

ObjectiveTo validate the efficacy of Seeplex HPV4A ACE for the detection of high-risk (HR) human papillomavirus (HPV) and HPV 16 and/or HPV 18 genotypes as compared to the PCR method and the Cervista HPV assays in cervical swab samples.MethodsBesides liquid-based cytology, additional 97 cervical swab samples were collected for HPV genotyping by HPV4A ACE, Cervista HPV assays, and PCR method. To check the statistical differences, we also conducted the paired proportion test, Cohen's κ statistic, and a receiver operating characteristic curve.ResultsSeeplex HPV4A ACE and the Cervista HPV HR showed substantial agreement with PCR for detection of HR HPVs (88.3%, κ=0.767 and 81.7%, κ=0.636, respectively). Seeplex HPV4A ACE also showed substantial agreement with the Cervista HPV 16/18 test (89.5%, κ=0.628). Additionally, the sensitivity and specificity of Seeplex HPV4A ACE and Cervista HPV HR were 91.4% vs. 84.5% and 73.4%, vs. 72.7%, respectively, when those higher than low-grade squamous intraepithelial lesions were regarded as abnormalities. HPV genotyping for HPV 16/18 detected cervical intraepithelial neoplasias (CINs) better than HR HPV tests (66.7% vs. 24.6% by HPV4A ACE, 52.6% vs. 25.9% by Cervista HPV assays in CIN II or more, relatively).ConclusionSeeplex HPV4A ACE is an effective method as the PCR and the Cervista HPV assays for the detection of HR HPVs and for genotyping of HPV 16 and 18.

Rate of detection of high-risk HPV with two assays in women ≥ 30 years of age

Background High-risk (HR) human papillomavirus (HPV) prevalence rates, as determined by the Cervista ® HPV HR test, in women aged ≥30 years in a routine screening population have not been studied. Objectives The primary objective of this study was to estimate HR HPV prevalence in women negative for intraepithelial lesion or malignancy (NILM) cytology using the CERVISTA HPV HR test. The study also compared HR HPV prevalence rates in women aged ≥30 years and NILM cytology using the CERVISTA HPV HR and Hybrid Capture ® 2 (hc2) tests. Study design A multi-center study was conducted to analyze HR HPV prevalence rates using the CERVISTA HPV HR test from residual ThinPrep ® specimens. HR HPV positive rates were determined for hc2; percent agreement between the CERVISTA HPV HR and the hc2 tests were reported. Results HR HPV prevalence rates among women with NILM cytology were not statistically different between the CERVISTA HPV HR and hc2 tests (6.92% [98/1417] versus 5.93% [84/1417], respectively; P > 0.05). The overall percent agreement between the tests was 95.3% (1351/1417; 95% confidence interval [CI]: 94.1–96.3; κ = 0.61, 95% CI: 0.53–0.70). There were no statistically significant differences between tests across age groups or investigational sites. For both tests, there was a statistically significant decrease in HR HPV positive results as age increases (CERVISTA HPV HR, P = 0.0009; hc2, P < 0.0001). Discussion There is no statistically significant difference between HR HPV prevalence rates obtained with the CERVISTA HPV HR and hc2 tests in women aged ≥30 years with NILM cytology.

Clinical Validation of the Cervista HPV HR and 16/18 Genotyping Tests for Use in Women With ASC-US Cytology

Abstract Objective High-risk (HR) human papillomavirus (HPV) testing is important in cervical cancer screening for triage to colposcopy. This study evaluated the clinical performance of the Cervista® HPV HR and 16/18 genotyping tests for detection of HPV in cervical cytology specimens. Methods The tests were prospectively evaluated in a multicenter clinical study. DNA was extracted from approximately 4000 residual liquid-based cytology specimens collected during routine liquid-based Papanicolaou tests at standard of care visits and was assessed for the presence of HR HPV and/or HPV types 16 and 18. All women with cytology results of atypical squamous cells of undetermined significance (ASC-US) or greater underwent colposcopic examination and biopsies were collected. Test results were compared with local colposcopy and histology results from a central pathology review panel. Results There were 1347 subjects with complete data sets of cytology, HR HPV, colposcopy, and histology included in the analysis of the HPV HR test. Sensitivity of the HPV HR test for detection of cervical intraepithelial neoplasia (CIN) 2+ among women with ASC-US cytology was 92.8% (95% confidence interval [CI]: 84.1–96.9) and the negative predictive value (NPV) was 99.1% (95% CI: 98.1–99.6). Sensitivity for detection of ≥CIN 3 in women with ASC-US was 100% (95% CI: 85.1–100) and the NPV was 100% (95% CI: 99.4–100). The specificity of the test for detection of ≥CIN 2 and ≥CIN 3 was 44.2% (95% CI: 41.5–46.9) and 43% (95% CI: 40.3–45.7), respectively. The HPV 16/18 genotyping test also performed as expected in women with ASC-US cytology who were positive for HR HPV. Conclusion The Cervista® HPV HR test can be clinically used for detecting HR HPV types in conjunction with cervical cytology for use in triage of women with ASC-US cytology during routine cervical cancer screening.

Clinical Experience with the Cervista HPV HR Assay: Correlation of Cytology and HPV Status from 56,501 Specimens

Testing for high-risk (HR) human papillomavirus (HPV) is a key component of current recommendations for cervical cancer screening. Herein is described our clinical experience using Cervista HPV HR, a testing platform recently approved by the US Food and Drug Administration for clinical use. Using data from a high-volume commercial laboratory, a retrospective analysis of cytologic and Cervista HPV HR test results from 56,501 samples was performed, and an indirect comparison was made with previous experience with 53,008 samples tested using the Hybrid Capture 2 platform. Of samples analyzed using Cervista HPV HR, 1.5% were of insufficient volume for testing and 1.1% yielded an insufficient signal from the internal control to be reported. In samples with a cytological interpretation of atypical squamous cells of undetermined significance, 48.5% (95% confidence interval [CI], 47.5 to 49.5) tested positive using Cervista HPV HR, compared with 59.4% (95% CI, 58.3 to 60.5) of samples using Hybrid Capture 2. Of samples from women aged 30 years or older with a negative cytological interpretation, 5.8% (95% CI, 5.6 to 6.1) tested positive using Cervista HPV HR, compared with 5.5% (95% CI, 5.3 to 5.7) of samples using Hybrid Capture 2. When stratified by five-year age groups between 30 and 65 years, positivity rates for high-risk human papillomavirus were similar in the Cervista HPV HR and Hybrid Capture 2 populations, and were consistent with expectations established by the literature.