On tests of equivalence via non‐unity relative risk for matched‐pair design

Tang, Niansheng; Tang, Man‐Lai; Chan, Ivan S. F.

doi:10.1002/sim.1213

Cited by 91 publications

(105 citation statements)

References 19 publications

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“…24,25 A minimum of 300 high-risk HPV-positive women needed to be included at a rejection rate α of 0.05. Histologically confirmed ≥ CIN3 was used as primary study endpoint.…”

Section: Discussionmentioning

confidence: 99%

“…Non-inferiority was defined as a relative sensitivity or specificity of at least 90% using a matched-sample score test. 24,25 We considered three factors that might influence sensitivity and specificity of the described tests. First, the age of the participants (aged ≥30 years vs o 30 years); second, the reason of referral to the gynecologist (non-cervix-related gynecologic complaints vs a recent abnormal cytology result in cervical screening); and third, the moment that the cervical scrape was collected (during a separate visit before colposcopy vs combined with the colposcopy procedure in one visit).…”

Section: Discussionmentioning

confidence: 99%

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p16/Ki-67 dual-stained cytology for detecting cervical (pre)cancer in a HPV-positive gynecologic outpatient population

et al. 2016

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Women who test positive for a high-risk type of the human papillomavirus (HPV) require triage testing to identify those women with cervical intraepithelial neoplasia grade 3 or cancer (≥ CIN3). Although Pap cytology is considered an attractive triage test, its applicability is hampered by its subjective nature. This study prospectively compared the clinical performance of p16/Ki-67 dual-stained cytology to that of Pap cytology, with or without HPV16/18 genotyping, in high-risk HPV-positive women visiting gynecologic outpatient clinics (n = 446 and age 18-66 years). From all women, cervical scrapes (for Pap cytology, HPV16/18 genotyping, and p16/Ki-67 dual-stained cytology) and colposcopy-directed biopsies were obtained. The sensitivity of p16/Ki-67 dual-stained cytology for ≥ CIN3 (93.8%) did neither differ significantly from that of Pap cytology (87.7%; ratio 1.07 and 95% confidence interval (CI): 0.97-1.18) nor from that of Pap cytology combined with HPV16/18 genotyping (95.1%; ratio 0.99 and 95% CI: 0.91-1.07). However, the specificity of p16/Ki-67 dual-stained cytology for ≥ CIN3 (51.2%) was significantly higher than that of Pap cytology (44.9%; ratio 1.14 and 95% CI: 1.01-1.29) and Pap cytology combined with HPV16/18 genotyping (25.8%; ratio 1.99 and 95% CI: 1.68-2.35). After exclusion of women who had been referred because of abnormal Pap cytology, the specificity of p16/Ki-67 dual-stained cytology for ≥ CIN3 (56.7%) remained the same, whereas that of Pap cytology (60.3%) increased substantially, resulting in a similar specificity of both assays (ratio 0.94 and 95% CI: 0.83-1.07) in this sub-cohort. In summary, p16/Ki-67 dual-stained cytology has a good clinical performance and is an interesting objective microscopybased triage tool for high-risk HPV-positive women. Persistent infection with a high-risk type of the human papillomavirus (HPV) is essential for the development of almost all cervical cancers. 1,2 Testing for high-risk HPV has been shown to provide superior protection against cervical intraepithelial neoplasia grade 3 and cervical cancer (together referred to as ≥ CIN3) compared with cervical cytology (Pap cytology). 3 However, most women who test positive for high-risk HPV clear the virus spontaneously and do not develop clinically relevant cervical disease. Therefore, additional triage testing is required to identify the subgroup of high-risk HPVpositive women who actually have ≥ CIN3, thereby Correspondence: Professor CJLM Meijer, MD PhD,

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“…24,25 A minimum of 300 high-risk HPV-positive women needed to be included at a rejection rate α of 0.05. Histologically confirmed ≥ CIN3 was used as primary study endpoint.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

p16/Ki-67 dual-stained cytology for detecting cervical (pre)cancer in a HPV-positive gynecologic outpatient population

et al. 2016

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“…To compare the clinical sensitivity and specificity for ՆCIN2 of the Abbott RealTime HR HPV test to that of HR HC2, a noninferiority score test (P Ͻ 0.05) was performed (22). The thresholds used for noninferiority were 90 and 98% for relative sensitivity and specificity, respectively.…”

Section: Methodsmentioning

confidence: 99%

Comparison of Clinical Performance of Abbott RealTi m e High Risk HPV Test with That of Hybrid Capture 2 Assay in a Screening Setting

et al. 2011

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The noninferiority score test revealed that the clinical sensitivity and specificity of the Abbott RealTime HR HPV test were not inferior (P ‫؍‬ 0.004 and 0.009, respectively) to those of HR HC2. Overall agreement between the two assays was 96.5%, with a k value of 0.86 (CI 95%, 0.82 to 0.91). We evaluated the intralaboratory reproducibility by retesting 521 samples at least 4 weeks after the first test; the crude agreement between the first and second test was 98.5%, with an overall k value of 0.97 (CI 95%, 0.95 to 0.99). This test fully satisfies the requirements of a primary cervical cancer screening test. This assay differentiates between HPV16, HPV18, and non-HPV16/18 types in every specimen, but how to use this information in a screening setting still is unclear.The etiologic link between persistent high-risk human papillomavirus (HR HPV) infections and cervical cancer and its immediate precancerous lesions has been widely demonstrated. A recent IARC classification reports solid evidence for a causal link to cervical cancer for only 12 HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59), which are defined as high-risk HPV (2).Large randomized trials produced sound evidence about the efficacy of screening with an HPV DNA test in reducing cervical cancer incidence (19) and mortality (20). According to trial results, an HPV test used as a cervical cancer screening test has three advantages: a higher long-term negative predictive value (NPV) that permits extending the screening interval without increasing the interval risk of cancer, a clinical sensitivity of 90 to 95% for cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) (1,3,6,7,13,17,18), and a marked reduction of CIN2/3 and cancer among test-negative women in the subsequent screening round (19).Several studies (12, 21) suggest that infections supported by HPV16 and HPV18 are associated with a higher risk for the progression of cervical cancer. Consequently, the genotyping of HPV16 and HPV18 has been proposed to guide the management of HPV-positive women throughout the follow-up procedures (12). Usually, viral tests are used to understand the etiology of symptomatic diseases. However, the HR HPV test in screening is aimed at preventing cervical cancer in an asymptomatic population, therefore it is useful only when it is able to detect clinically relevant infections. In other words, HPV testing for screening purposes needs optimal balance between clinical sensitivity and specificity. At present, the HPV assays considered clinically validated for screening purposes are the hybrid capture 2 HPV test (HC2) and the GP5ϩ/6ϩ-PCR enzyme immunoassay (EIA) (24). New candidate assays should prove their value in large prospective screening studies or should prove to be noninferior to a validated reference assay in clinical equivalence studies on specimens from a cervical screening cohort. An international consortium recently published guidelines (14) defining the appropriate study design and sample size to measure the sensitivity, specificity, and re...

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“…The relative sensitivity and specificity of the Xpert HPV were compared to those of the standard comparator test (SCT) to determine whether these measures were lower than 0.90 and 0.98, respectively. Noninferiority was assessed by a one-sided statistical test for matched data (14). The null hypothesis of inferiority of the Xpert HPV was rejected if P for noninferiority was Ͻ 0.05.…”

Section: Assessment Of Clinical Performance and Comparison With A CLImentioning

confidence: 99%

Performance of a Cartridge-Based Assay for Detection of Clinically Significant Human Papillomavirus (HPV) Infection: Lessons from VALGENT (Validation of HPV Genotyping Tests)

et al. 2016

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On tests of equivalence via non‐unity relative risk for matched‐pair design

Cited by 91 publications

References 19 publications

p16/Ki-67 dual-stained cytology for detecting cervical (pre)cancer in a HPV-positive gynecologic outpatient population

p16/Ki-67 dual-stained cytology for detecting cervical (pre)cancer in a HPV-positive gynecologic outpatient population

Comparison of Clinical Performance of Abbott RealTi m e High Risk HPV Test with That of Hybrid Capture 2 Assay in a Screening Setting

Performance of a Cartridge-Based Assay for Detection of Clinically Significant Human Papillomavirus (HPV) Infection: Lessons from VALGENT (Validation of HPV Genotyping Tests)

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