Impact of the more restrictive definition of atypical squamous cells introduced by the 2001 Bethesda System on the sensitivity and specificity of the Papanicolaou test

Thrall, Michael J.; Pambuccian, Stefan E.; Stelow, Edward B.; McKeon, Dan M.; Miller, Lizette; Savik, Kay; Gulbahce, H. Evin

doi:10.1002/cncr.23538

Cited by 12 publications

(7 citation statements)

References 38 publications

(36 reference statements)

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“…Sensitivity for CIN2+ was 73% (95% CI 64.7–80%) in the laboratory with the highest overall abnormal rate (9.9%), but only 42% (95% CI 33.9–50.5%) in the laboratory with the lowest abnormal rate (3·8%). Although it has previously been shown that “judicious downgrading” to NILM of cytology specimens previously classified as ASC‐US will result in nonsignificant reductions in the sensitivity of cervical cytology for CIN2+, to our knowledge, this is the first study to clearly document that the sensitivity of cervical cytology is considerably lower in laboratories with a low overall abnormal rate compared with those with a high abnormal rate. The difference in sensitivity between the laboratories cannot be attributed to underlying differences in their patient populations since LBC specimens screened at each laboratory came from participants with a similar demographic makeup and a similar prevalence of hrHPV (14 pooled genotypes), HPV 16 and HPV 18.…”

Section: Discussionmentioning

confidence: 69%

Interlaboratory variation in the performance of liquid-based cytology: Insights from the ATHENA trial

et al. 2013

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Although it is recognized that cervical cytology is highly subjective, and that there is considerable interlaboratory variation in how slides are evaluated, little is known as to how this impacts the performance of cytology. In the ATHENA trial, liquid-based cytology specimens from 46,887 eligible women !21 years of age were evaluated at four large regional US laboratories, providing a unique opportunity to evaluate the impact of interlaboratory variations on the performance of cervical cytology. All women with abnormal cytology (atypical squamous cells of undetermined significance or higher) were referred to colposcopy, as were all high-risk human papillomavirus (hrHPV)-positive women !25 years of age and a random subset of those !25 years of age who were negative by both hrHPV testing and cytology. Sociodemographics, risk factors for cervical disease, and prevalence of cervical intraepithelial neoplasia (CIN) were similar across the laboratories. There were considerable differences among the laboratories both in overall cytological abnormal rates, ranging from 3.8 to 9.9%, and in sensitivity of cytology to detect CIN grade 2 or worse (CIN21), from 42.0 to 73.0%. In contrast, the hrHPV positivity rate varied only from 10.9 to 13.4%, and the sensitivity of hrHPV testing from 88.2 to 90.1%. These observations suggest that hrHPV testing without cytology should be considered as the initial method for cervical cancer screening.It is widely recognized that cervical cytology is highly subjective, and that this results in considerable interlaboratory variation in the rate of cytological abnormalities. A 2006 survey by the College of American Pathology (CAP) found that the median atypical squamous cells of undetermined significance (ASC-US) rate in different US cytology laboratories varied from 1.7% (lowest 5th percentile of laboratories) to 9.6% (upper 95th percentile of laboratories).1 The median ASC-US rate in the United States at that time was 4.9%. Relatively little is known about how this interlaboratory variation in the rate of cytological abnormalities impacts the performance of cytology for detecting cervical intraepithelial neoplasia (CIN) 2,3 lesions and cervical cancer (CIN21). This is not surprising since there continues to be considerable controversy in the cervical cancer screening community as to the performance of cervical cytology in a "real-world" setting. A metaanalysis published in 1995 reported that the sensitivity of conventional cervical cytology was 49% and the specificity was 62%.2 In 2000, Nanda et al. evaluated the performance of cervical cytology with another meta-analysis for the US Preventive Services Task Force that included studies utilizing liquid-based cytology.3 This meta-analysis found that in the least biased studies, the sensitivity of cytology varied from 30 to 87%, and specificity ranged from 86 to 100%. Such a wide range of performance estimates in different studies is not unexpected given the inherent difficulty of determining the underlying prevalence of high-grade cervical in...

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Section: Discussionmentioning

confidence: 69%

Interlaboratory variation in the performance of liquid-based cytology: Insights from the ATHENA trial

et al. 2013

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“…Thrall et al. reported that 32% smears were downgraded to NILM upon review and 9.3% upgraded to SIL 9 …”

Section: Discussionmentioning

confidence: 99%

Atypical squamous cells and low-grade squamous intraepithelial lesion in cervical cytology: cytohistological correlation and implication for management in a low-resource setting

Gupta¹,

Srinivasan²,

Nijhawan³

et al. 2010

Cytopathology

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“…Pathological examination was done by an experienced pathologist. Results were classified into 6 grades according to The Bethesda System (TBS): within normal limit (WNL); atypical squamous cells of undetermined significance (ASCUS); atypical glandular cells of undetemined significance (AGUS); low grade squamous intraepithelial lesion (LSIL); high grade squamous intraepithelial lesion (HSIL); squamous cell carcinoma (SCC) (Thrall et al, 2001). …”

Section: Methodsmentioning

confidence: 99%

Efficacy of Pap Test in Combination with ThinPrep Cytological Test in Screening for Cervical Cancer

Chen

Shu²,

Chang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Impact of the more restrictive definition of atypical squamous cells introduced by the 2001 Bethesda System on the sensitivity and specificity of the Papanicolaou test

Cited by 12 publications

References 38 publications

Interlaboratory variation in the performance of liquid-based cytology: Insights from the ATHENA trial

Interlaboratory variation in the performance of liquid-based cytology: Insights from the ATHENA trial

Atypical squamous cells and low-grade squamous intraepithelial lesion in cervical cytology: cytohistological correlation and implication for management in a low-resource setting

Efficacy of Pap Test in Combination with ThinPrep Cytological Test in Screening for Cervical Cancer

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