Cervista Human Papillomavirus Research Articles

Detection accuracy of the Cobas HPV assay for high-risk HPV in head and neck FNA biopsy specimens.

This study evaluated the detection accuracy of the Cobas human papillomavirus (HPV) assay for high-risk human papillomavirus (hrHPV) and HPV-16 in head and neck fine-needle aspiration (FNA) specimens with squamous cell carcinoma. Head and neck FNA biopsy specimens from 2012 to 2020 were retrospectively collected. Cobas HPV testing was performed on 90 FNA specimens with valid Cervista HPV testing results. Results of Cobas HPV and Cervista HPV assays were compared. A Linear Array or SPF10-LiPA25 HPV genotyping assay resolved cases with discrepant results. The κ value and accuracy of Cobas HPV testing were calculated. The accuracy of the Cobas HPV assay was also determined in 42 FNA needle-rinse specimens. Cobas HPV was positive in 82% of the FNA specimens (74 of 90). The concordance between Cobas HPV and Cervista HPV test results was 88.9% (80 of 90) with substantial agreement (κ = 0.669; 95% CI, 0.481-0.856). With HPV genotyping confirmation in cases with discrepant results between the 2 HPV assays, Cobas HPV showed 100% sensitivity and specificity for hrHPV. HPV-16 was detected in 88% of HPV-positive cases (65 of 74). HPV genotyping confirmed 1 false-negative HPV-16 result and 1 false-positive HPV-16 result. Overall, the accuracy of Cobas HPV for HPV-16 was 97.8%. The accuracy of Cobas HPV in FNA needle-rinse specimens was 100%. The Cobas HPV assay is highly accurate for determining the HPV status in head and neck FNA specimens. FNA needle rinse is valid for Cobas HPV testing in patients with squamous cell carcinoma.

Validation of cobas 4800 HPV assay in SurePath Papanicolaou specimens for cervical cancer screening

The cobas (Roche Diagnostics, Indianapolis, IN) HPV assay was approved by the US Food and Drug Administration for human papillomavirus (HPV) testing in SurePath (Becton Dickinson, Franklin Lakes, NJ) Papanicolaou specimens for cervical cancer prevention. To validate the cobas HPV assay in SurePath specimens in our institution, we compared its accuracy and clinical efficacy to that of the Cervista (Hologic, Marlborough, MA) HPV HR assay. This study used 138 Papanicolaou (Pap) cytology specimens collected in SurePath preservative fluid at our institution in 2018. After Pap cytology testing, the residual specimens were split for testing with the cobas and Cervista assays. Polymerase chain reaction (PCR)-based HPV testing (GP5+/GP6+) was performed on specimens with discrepant results. Clinical follow-up data were reviewed. The cobas HPV and Cervista HPV HR assays showed good concordance (89.1%), with a kappa value of 0.78 (95% CI: 0.675-0.885). Fifteen specimens showed discrepant results between the 2 assays. Of 7 cases with cobas+/Cervista- results, 5 (71%) were confirmed positive by PCR. Of 8 cases with cobas-/Cervista+ results, 4 (50%) were confirmed positive by PCR. cobas HPV and Cervista HPV HR showed the same HPV-positive rate in cases of pathologically diagnosed ASC-H, LSIL, or HSIL. The sensitivities and specificities for detecting high-risk HPV of cobas HPV (93.7%, 97.3%) and Cervista HPV HR (92.1%, 94.7%) were comparable. The cobas HPV assay had false-negative results in 4 cases (5.2%) including 1 false-negative case that failed to predict CIN3. The cobas HPV assay is valid in SurePath Pap cytology specimens for cervical cancer screening but has limitations of false-negative results with clinical implications.

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.

Incorporation of Cervista Human Papillomavirus 16/18 Assay Into Algorithms for Classifying Human Papillomavirus Status in Formalin-Fixed, Paraffin-Embedded Head and Neck Squamous Carcinoma Specimens.

Human papillomavirus (HPV) DNA in situ hybridization (ISH) assay and p16 immunohistochemistry (IHC) are used to determine high-risk HPV status in formalin-fixed, paraffin-embedded (FFPE) tissues in oropharyngeal squamous cell carcinoma (SCC). Although high sensitivity and specificity for HPV can be obtained by combined p16 IHC and HPV DNA ISH, the occasional discrepancy between these assays has prompted evaluation of Cervista HPV assays in FFPE tissue from patients with oropharyngeal SCC. To compare the efficacy of Cervista HPV 16/18 and Cervista HPV HR assay to that of HPV DNA ISH assay and p16 IHC in FFPE tissue in head and neck squamous cell carcinoma of oropharyngeal origin. Archived FFPE tissue from 84 patients with SCC of oropharyngeal origin and available HPV DNA ISH and p16 IHC test results were tested with the Cervista HPV 16/18 assay and further verified by polymerase chain reaction (PCR)-based HPV16/18 genotyping tests in cases with discrepancy. Of the 84 specimens, 75% (63 of 84) were positive and 16% (13 of 84) had discrepant or equivocal findings by p16 IHC and HPV DNA ISH testing. Use of Cervista HPV assays, either to clarify discrepant/equivocal findings or as confirmation after initial p16 IHC/HPV DNA ISH tests, identified 81% (68 of 84) of HPV-positive cases without equivocal HPV results. Five of 13 cases with discrepancy or equivocal HPV DNA ISH results tested positive for HPV16 or HPV18 by Cervista HPV 16/18 assay, which was further confirmed by PCR-based HPV 16/18 genotyping. The Cervista HPV assays are a reasonable alternative to HPV DNA ISH in determining HPV status in FFPE tissue specimens from patients with oropharyngeal SCC.

Immediate histopathologic follow-up of cervista and aptima high-risk HPV assays in women with LSIL cytology.

Recent guidelines recommended the optional deferral of colposcopy for postmenopausal women with low-grade squamous intraepithelial lesion (LSIL) Papanicolaou (Pap) test results and negative human papillomavirus (HPV) testing. The objective of the current study was to assess the histopathologic follow-up of Cervista and Aptima high-risk HPV (hrHPV) testing in patients with LSIL cytology. Women with LSIL Pap test results and Cervista or Aptima hrHPV testing results were retrospectively identified from June 2013 through July 2017. Histological follow-up results within 6 months after LSIL Pap tests were analyzed. A total of 1731 and 1906 cases of LSIL Pap tests, respectively, were tested on Cervista and Aptima platforms. Among the 2119 cases with histopathologic follow-up, cervical intraepithelial neoplasia of types 2/3 (CIN2/3) was diagnosed in 184 women (8.9%) and the detection rate was significantly higher in women with positive HPV testing compared with those with a negative result on both assays. Both methods demonstrated comparable performance for detecting CIN2/3 lesions. However, in women aged ≥50 years, the specificity for the detection of CIN2/3 lesions by the Aptima assay was statistically significantly higher than that of the Cervista test (48.7% vs 23.1%; P<.01), although there were no significant differences in the sensitivity, positive predictive value, and negative predictive value between these 2 assays in this age group. The Aptima assay was found to be statistically significantly more specific than the Cervista test for detecting CIN2/3 lesions among women aged ≥50 years. These findings not only further support the recommendations by the American Society for Colposcopy and Cervical Pathology that hrHPV triage is an acceptable option for postmenopausal women with LSIL cytology, but also provide additional evidence that HPV RNA testing may be more useful in clinical risk stratification due to its specificity in the postmenopausal population. Cancer Cytopathol 2018. © 2018 American Cancer Society.

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.

Evaluation of careHPV, Cervista Human Papillomavirus, and Hybrid Capture 2 Methods in Diagnosing Cervical Intraepithelial Neoplasia Grade 2+ in Xinjiang Uyghur Women

The study aimed to evaluate the value of the Cervista human papillomavirus (HPV), Hybrid Capture 2 (HC-2), and careHPV tests in diagnosing cervical intraepithelial neoplasia grade 2 (CIN2) or worse in Xinjiang Uyghur women. Three high-risk human papillomavirus (HR-HPV) detection methods were studied on two different populations by different combination modes; a cytology specimen was obtained at the same time. An abnormal result of any test resulted in referral to colposcopy. Cervical biopsy was also performed. In population 1, HR-HPV-positive rates were 57.6% and 54.3% as detected by HC-2 and Cervista, respectively; κ = 0.892 for consistency check of HC-2 and Cervista (p < .001). Area under the receiver operating characteristic curve (AUC) of HC-2 and Cervista was 0.744 (95% confidence interval [CI]: 0.664∼0.824, p < .001) and 0.786 (95% CI: 0.715∼0.858, p < .001), respectively, for diagnosing CIN2+. The A9 probe can detect six subtypes of HPV, including HPV16, HPV31, HPV33, HPV35, HPV52, and HPV58. If one or more of these subtypes are postitive, then A9 will be positive. A diagnosis of class A9 by the Cerevista test correlated with pathological interpretations (chi-square = 43.063, p < .001). In population 2, HR-HPV-positive rates were 40.1% and 34.4%, respectively, by HC-2 and careHPV; κ value was 0.779 for the two tests (p < .001). AUC of HC-2 was 0.895 (95% CI: 0.849∼0.940, p < .001), and careHPV was 0.841 (95% CI: 0.770∼0.899, p < .001) for diagnosing CIN2+. Good consistency was shown between HC-2 and Cervista tests and also between the HC-2 and careHPV tests. In the detection of CIN2+, Cervista showed better specificity than HC-2, and interpretation of the A9 subgroup showed high predicted value. The HC-2 test demonstrated better sensitivity than careHPV in detection of CIN2+. HC-2, Cervista, and careHPV may be applied as a triage test for visual inspection with acetic acid/Lugol's iodine-positive or ThinPrep cytologic test-positive women. The careHPV test was comparatively economical and efficient and may be more suitable for resource-limited regions, such as Xinjiang. This study was designed to evaluate the value of the Cervista human papillomavirus (HPV), Hybrid Capture 2 (HC-2), and careHPV tests in diagnosing cervical intraepithelial neoplasia grade 2 (CIN2) or worse (CIN2+) lesions in Xinjiang Uyghur women. Results showed that there was good consistency between the HC-2 and Cervista tests, as well as between the HC-2 and careHPV tests. In detecting CIN2+, Cervista had higher specificity than HC-2, whereas analysis of the A9 subgroup had high predictive value. (The A9 probe can detect six subtypes of HPV, including HPV16, HPV31, HPV33, HPV35, HPV52, and HPV58. If one or more of these subtypes are postitive, then A9 will be positive.) The HC-2 test demonstrated better sensitivity than careHPV in detecting CIN2+. HC-2, Cervista, and careHPV could be applied as a triage test for visual inspection with acetic acid/Lugol's iodine-positive or ThinPrep cytologic test-positive women. The careHPV test was comparatively economical and efficient and may be more suitable for resource-limited regions, such as Xinjiang.

Cell Block Preparation versus Liquid-Based Thin-Layer Cervical Cytology: A Comparative Study Evaluating Human Papillomavirus Testing by Hybrid Capture-2/Cervista, in situ Hybridization and p16 Immunohistochemistry

Objective: Cell block (CB) preparations from residual liquid-based Pap samples have been shown to be of diagnostic value. In this study we evaluated human papillomavirus (HPV) in situ hybridization (ISH) and p16 immunohistochemistry (IHC) on CB preparations and compared the results with the primary diagnosis and standard HPV tests. Design: In total, 197 HE-stained CB slides prepared from CBs from residual Pap samples (152 ASCUS, 2 ASC-H, 32 LGSIL, 4 HGSIL, 1 AGUS and 6 normal) were analyzed. Hybrid Capture-2 (HC-2)/Cervista testing and HPV ISH and p16 IHC were performed on the CB samples. The test performance characteristics were compared with HPV and p16 assay performances. Results: The cellular architecture was well maintained in CBs with excellent consistency. HPV ISH testing had an excellent concordance with the HC-2/Cervista methods (85%) with high sensitivity (82.6%; 95% CI 75.9, 89.4) and specificity (89.3%). Of all the p16 tests, 38% were positive (60 out of 159 samples). The overall concordance between p16 and HC-2/Cervista (64%), or between p16 and ISH (68%), was lower than the concordance between ISH and HC-2/Cervista (85%). Conclusions: HPV ISH and p16 IHC testing is feasible, cost effective and practical. A combination of the two tests would ultimately improve diagnostic accuracy, leading to better therapeutic decisions.

The Utility of Cervista Human Papillomavirus Assay in Necrotic Fine-needle Aspiration Specimens of Metastatic Squamous Cell Carcinoma from Neck Lymph Nodes

The Utility of Cervista Human Papillomavirus Assay in Necrotic Fine-needle Aspiration Specimens of Metastatic Squamous Cell Carcinoma from Neck Lymph Nodes

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.

Human papillomavirus (HPV) assays for testing fine‐needle aspiration specimens in patients with head and neck squamous cell carcinoma

Human papillomavirus (HPV)‐related head and neck squamous cell carcinoma is frequently diagnosed by fine‐needle aspiration, and accurate methods for confirming high‐risk HPV types in these cytologic specimens are needed. Authors in this issue demonstrate the validity of the Cervista HPV assays for identifying these HPV types.

High-Risk Human Papillomavirus DNA Detected in Primary Squamous Cell Carcinoma of Urinary Bladder

We reported previously that more than one-third (37%) of primary bladder squamous cell carcinomas (SCCs) demonstrate diffuse p16 immunoreactivity independent of gender. This observation made us question whether p16 overexpression in bladder carcinoma is due to human papillomavirus (HPV)-dependent mechanisms. To determine whether the presence of high-risk HPV (HR-HPV) DNA could be detected in these tumor cells. Fourteen cases of primary bladder SCC, which were positive for p16 by immunohistochemistry, were probed for the detection of HR-HPV by in situ hybridization and the signal amplification Invader assay. Samples positive for detection of HR-HPV by Invader assay were amplified by using HR-HPV type-specific primers, and amplification products were DNA sequenced. Detection of HR-HPV by the in situ hybridization method was negative in all cases (0 of 14). However, in 3 of 14 cases (21.4%), the presence of HR-HPV DNA was detected with the Cervista HPV HR Invader assay, which was followed by identification of genotype. All positive cases were confirmed by using HR-HPV type-specific amplification followed by DNA sequencing. Identified HR-HPV genotypes included HPV 16 (2 cases) and HPV 35 (1 case). High-risk HPV DNA is detectable in a subset of primary bladder SCCs. Based on the well-documented carcinogenic potential of HR-HPV, there is a necessity for additional studies to investigate the role of HR-HPV in bladder carcinogenesis.

OP041: Impact of human papillomavirus (HPV) and p16 status on survival and response with cisplatin plus 5-FU and cetuximab in recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Analysis of the phase III extreme trial

Purpose Retrospective analysis to assess the role of tumor HPV/p16 status in patients (pts) with R/M SCCHN receiving cisplatin+5-FU chemotherapy (CT)+/−cetuximab. Material and methods Cervista HPV 16/18 and HPV high-risk assays and IHC detection of p16INK4A were used to determine tumor HPV/p16 status. Results Of 442 pts in the trial, p16 status was available for 381 and HPV status for 321. For survival, hazard ratios in favor of CT+cetuximab were seen in HPV−, HPV+, p16− and p16+ subgroups ( Table 1 ). Interaction tests confirmed the treatment effect of CT+cetuximab vs CT was independent of tumor HPV or p16 status. Similar findings were made for PFS (interaction test p = 0.98 for HPV and p = 0.43 for p16: no significant interaction was noted). CT+cetuximab also improved the chances of achieving a response across all subgroups ( Table 1 ). Within the CT+cetuximab and CT arms, HPV+/p16+ status was associated with a more favorable outcome than HPV−/p16− status. Conclusion Although the number of HPV+/p16+ pts was low, the results suggest that the survival benefits of CT+cetuximab vs CT are independent of tumor HPV/p16 status but that HPV+/p16+ status seems associated with a more favorable outcome than HPV−/p16− status.

Effect of Glacial Acetic Acid Treatment of Liquid-Based Cytology Collections on Performance of Cervista HPV HR for Detection of High-Risk Human Papillomavirus

Inadequate cervical cytological analysis can be facilitated by glacial acetic acid (GAA) treatment of primary liquid-based collections to remove mucus, erythrocytes, inflammatory cells, and cellular debris. In the context of a commercial human papillomavirus (HPV) hybridization assay performed on 465 tandem specimens with and without GAA treatment, we show that GAA treatment significantly reduces genomic DNA content (P < 0.0001) and creates an increased potential for indeterminate and false-negative results. In the context of cytological workflow, laboratories should consider providing a specimen aliquot for HPV DNA detection prior to GAA treatment.

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.

Cervista HR and HPV 16/18 Assays vs Hybrid Capture 2 Assay

Sensitive and specific assays for human papillomavirus (HPV) are essential for patient management. In this study, we directly compared the efficacy of the Hybrid Capture 2 (HC2; Qiagen, Valencia, CA) and Cervista assays (Hologic, Madison, WI). Consecutive cervical cytology specimens (n = 601) were tested using HC2, Cervista HR, and Cervista HPV 16/18 with analysis of only cytology-negative cases (n = 533). Results indicated no significant difference (P = .458) in prevalence rates between HC2 (7.5%) and Cervista HR (8.5%). The Cervista 16/18 prevalence was 1.6%. The negative percentage of agreement was 95.1% (468/492) vs a 70% (28/40) positive percentage of agreement. No false-negative results were detected by the Cervista internal DNA control. Our data show 29 discordant positive results (12 HC2 and 17 Cervista HR), suggesting some women with negative cytology may be triaged for unnecessary follow-up with either assay. For clinical screening, Cervista HR and HC2 are comparable and, by extension, should provide excellent negative predictive value for histologically relevant disease.

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.

Age-Stratified Performance of the Cervista HPV 16/18 Genotyping Test in Women with ASC-US Cytology

The objective of this study was to evaluate the clinical performance of the Cervista HPV 16/18 genotyping test for detection of human papilloma virus (HPV) 16 and 18 in cervical cytology specimens in women stratified by age. In a multicenter, prospective clinical study, ThinPrep specimens were tested for the presence of HPV 16 and 18 using the HPV 16/18 genotyping test. Genotyping results from women with atypical squamous cells of undetermined significance or greater cytology were compared with local colposcopy and/or histology results. Sensitivity, specificity, and negative and positive predictive values (NPV and PPV) were determined. The prevalence of cervical intraepithelial neoplasia (CIN) 2(+) in subjects positive for HPV 16/18 was 6.6% and 4.1% for women <30 and ≥30 years of age, respectively. The sensitivity of the test was 70.0% (95% CI: 54.6-81.9) and 66.7% (95% CI: 46.7-82.0) in women <30 and ≥30 years, respectively. The NPV was 95.5% (95% CI: 93.4-97.6) in women <30 years and 96.6% (95% CI: 94.8-98.5) in women ≥30 years. Specificity was higher in women ≥30 years (79.9%; 95% CI: 74.9-84.2) than women <30 years (61.9%; 95% CI: 57.1-66.4). The PPV was 15.2% (95% CI: 12.7-19.1) in women <30 years and 21.9% (95% CI: 17.0-30.7) in women ≥30 years. The performance of the Cervista HPV 16/18 genotyping test for predicting ≥CIN 2 is what would be expected across the key ≥CIN 2 age strata. HPV 16/18 genotyping may help further stratify women with a greater potential to develop cervical cancer.

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.

Analytical performance of Cervista ® HPV 16/18 genotyping test for cervical cytology samples

Background Human papillomavirus (HPV) types 16 and 18 are the 2 most frequent types associated with cervical cancer. Identifying their presence or absence in cervical samples may assist in triaging women for subsequent management. The Cervista ® HPV 16/18 genotyping test specifically detects the presence of HPV 16 and 18 in ThinPrep ® cervical specimens. Objectives The objective was to establish the analytical performance of the CERVISTA HPV 16/18 genotyping test. Study design These studies were performed in support of a regulatory submission to the US Food and Drug Administration. Here we report the analytical sensitivity (limit of detection), accuracy compared to consensus L1 gene PCR/bi-directional sequencing, precision, reproducibility, and cross-reactivity (specificity) of the genotyping test. Results Analytical sensitivity for detection of HPV 16 and 18 ranged between 625 and 1250 copies/reaction for both types. When compared to PCR/sequencing for women with atypical squamous cells of undetermined significance cytology, the positive percent agreement was 94.1% (95% confidence interval [CI], 89.8–96.7) and the negative percent agreement was 85.7% (95% CI, 82.4–88.4). The test demonstrated high within-laboratory and inter-operator precision. Reproducibility within sites and between 3 testing sites resulted in 100% agreement with expected results (150 positive, 90 negative results). The genotyping test did not exhibit cross-reactivity to DNA from common low-risk HPV types and other microorganisms found in the human female reproductive tract. Conclusions These analytical performance data support the use of CERVISTA HPV 16/18 genotyping test for the detection and differentiation of HPV 16 and 18 in ThinPrep cervical cytology specimens.