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Triage of ASC-H : a meta-analysis of the accuracy of high-risk HPV testing and other markers to detect cervical precancer

(2016) CANCER CYTOPATHOLOGY. 124(4). p.261-272
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Abstract
BACKGROUND : Women with a cytological diagnosis of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) are usually immediately referred for colposcopy. However, triage may reduce the burden of the diagnostic workup and prevent overtreatment. METHODS : A meta-analysis was conducted to assess the accuracy of high-risk human papillomavirus (hrHPV) testing and testing for other molecular markers for the detection of grade 2 cervical intraepithelial neoplasia or worse (CIN2+) or grade 3 cervical intraepithelial neoplasia or worse (CIN3+) in women with ASC-H. An additional question that was assessed was whether triage would be useful in light of the relatively high pretriage probability of underlying precancer. RESULTS : The pooled absolute sensitivity and specificity of the Hybrid Capture 2 (HC2) assay for CIN2+(derived from 19 studies) were 93% (95% confidence interval [CI], 89%-95%) and 45% (95% CI, 41%-50%), respectively. p16(INK4a) staining (only 3 studies) had similar sensitivity (93%; 95% CI, 75%-100%) but superior specificity (specificity ratio, 1.69) to HC2 for CIN2+. Testing for paired box 1 gene methylation (only 1 study) showed a superior specificity of 95% (specificity ratio, 2.08). The average pretest risk was 34% for CIN2+and 20% for CIN3+. A negative HC2 result decreased this to 8% and 5%, respectively, whereas a positive result upgraded the risk to 47% and 28%, respectively. CONCLUSIONS : Because of the high probability of precancer with a diagnosis of ASC-H, the utility of triage is limited. The usual recommendation for referring women with ASC-H for colposcopy is not altered by a positive triage test, whatever test is used. A negative hrHPV DNA or p16(INK4a) test may allow repeat testing, but this recommendation will depend on local decision thresholds for referral. Cancer Cytopathol 2016;124:261-72. (c) 2015 American Cancer Society. Because of the high probability of precancer in patients with a diagnosis of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), the utility of triage is limited. The usual recommendation of referring women with ASC-H to colposcopy is not altered by a positive triage test, whatever test is used. A negative high-risk human papillomavirus DNA or p16(INK4a) test may allow repeat testing, but this recommendation will depend on local decision thresholds for referral.
Keywords
atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), cervical cancer, cervical intraepithelial neoplasia, diagnostic test accuracy, human papillomavirus (HPV), meta-analysis, triage, ATYPICAL SQUAMOUS-CELLS, PATHOLOGY SCREENING GUIDELINES, HUMAN-PAPILLOMAVIRUS GENOTYPES, GRADE INTRAEPITHELIAL LESION, AMERICAN-CANCER-SOCIETY, HYBRID-CAPTURE-II, FOLLOW-UP, 5-YEAR RISKS, UNDETERMINED SIGNIFICANCE, DIAGNOSTIC PERFORMANCE

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Citation

Please use this url to cite or link to this publication:

Chicago
Xu, Lan, Freija Verdoodt, Nicolas Wentzensen, Christine Bergeron, and Marc Arbyn. 2016. “Triage of ASC-H : a Meta-analysis of the Accuracy of High-risk HPV Testing and Other Markers to Detect Cervical Precancer.” Cancer Cytopathology 124 (4): 261–272.
APA
Xu, Lan, Verdoodt, F., Wentzensen, N., Bergeron, C., & Arbyn, M. (2016). Triage of ASC-H : a meta-analysis of the accuracy of high-risk HPV testing and other markers to detect cervical precancer. CANCER CYTOPATHOLOGY, 124(4), 261–272.
Vancouver
1.
Xu L, Verdoodt F, Wentzensen N, Bergeron C, Arbyn M. Triage of ASC-H : a meta-analysis of the accuracy of high-risk HPV testing and other markers to detect cervical precancer. CANCER CYTOPATHOLOGY. 2016;124(4):261–72.
MLA
Xu, Lan, Freija Verdoodt, Nicolas Wentzensen, et al. “Triage of ASC-H : a Meta-analysis of the Accuracy of High-risk HPV Testing and Other Markers to Detect Cervical Precancer.” CANCER CYTOPATHOLOGY 124.4 (2016): 261–272. Print.
@article{8500473,
  abstract     = {BACKGROUND : Women with a cytological diagnosis of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) are usually immediately referred for colposcopy. However, triage may reduce the burden of the diagnostic workup and prevent overtreatment. 
METHODS : A meta-analysis was conducted to assess the accuracy of high-risk human papillomavirus (hrHPV) testing and testing for other molecular markers for the detection of grade 2 cervical intraepithelial neoplasia or worse (CIN2+) or grade 3 cervical intraepithelial neoplasia or worse (CIN3+) in women with ASC-H. An additional question that was assessed was whether triage would be useful in light of the relatively high pretriage probability of underlying precancer. 
RESULTS : The pooled absolute sensitivity and specificity of the Hybrid Capture 2 (HC2) assay for CIN2+(derived from 19 studies) were 93% (95% confidence interval [CI], 89%-95%) and 45% (95% CI, 41%-50%), respectively. p16(INK4a) staining (only 3 studies) had similar sensitivity (93%; 95% CI, 75%-100%) but superior specificity (specificity ratio, 1.69) to HC2 for CIN2+. Testing for paired box 1 gene methylation (only 1 study) showed a superior specificity of 95% (specificity ratio, 2.08). The average pretest risk was 34% for CIN2+and 20% for CIN3+. A negative HC2 result decreased this to 8% and 5%, respectively, whereas a positive result upgraded the risk to 47% and 28%, respectively. 
CONCLUSIONS : Because of the high probability of precancer with a diagnosis of ASC-H, the utility of triage is limited. The usual recommendation for referring women with ASC-H for colposcopy is not altered by a positive triage test, whatever test is used. A negative hrHPV DNA or p16(INK4a) test may allow repeat testing, but this recommendation will depend on local decision thresholds for referral. Cancer Cytopathol 2016;124:261-72. (c) 2015 American Cancer Society. 
Because of the high probability of precancer in patients with a diagnosis of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), the utility of triage is limited. The usual recommendation of referring women with ASC-H to colposcopy is not altered by a positive triage test, whatever test is used. A negative high-risk human papillomavirus DNA or p16(INK4a) test may allow repeat testing, but this recommendation will depend on local decision thresholds for referral.},
  author       = {Xu, Lan and Verdoodt, Freija and Wentzensen, Nicolas and Bergeron, Christine and Arbyn, Marc},
  issn         = {1934-662X},
  journal      = {CANCER CYTOPATHOLOGY},
  keywords     = {atypical squamous cells,cannot exclude high-grade squamous intraepithelial lesion (ASC-H),cervical cancer,cervical intraepithelial neoplasia,diagnostic test accuracy,human papillomavirus (HPV),meta-analysis,triage,ATYPICAL SQUAMOUS-CELLS,PATHOLOGY SCREENING GUIDELINES,HUMAN-PAPILLOMAVIRUS GENOTYPES,GRADE INTRAEPITHELIAL LESION,AMERICAN-CANCER-SOCIETY,HYBRID-CAPTURE-II,FOLLOW-UP,5-YEAR RISKS,UNDETERMINED SIGNIFICANCE,DIAGNOSTIC PERFORMANCE},
  language     = {eng},
  number       = {4},
  pages        = {261--272},
  title        = {Triage of ASC-H : a meta-analysis of the accuracy of high-risk HPV testing and other markers to detect cervical precancer},
  url          = {http://dx.doi.org/10.1002/cncy.21661},
  volume       = {124},
  year         = {2016},
}

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