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Aqaa 069
Aqaa 069
From the Department of Pathology and Laboratory Medicine, Weill Cornell Medicine–New York Presbyterian Hospital, New York, NY.
DOI: 10.1093/AJCP/AQAA069
Key Points
ABSTRACT
• The study explores the impact of the implementation of the dual
Objectives: To evaluate the impact of implementing the interpretation of atypical squamous cells, cannot exclude high-grade
squamous intraepithelial lesion (ASC-H) and low-grade squamous
dual interpretation of atypical squamous cells, cannot intraepithelial lesion (LSIL) after the Bethesda System 2014 and
exclude high-grade squamous intraepithelial lesion (ASC- compares it with other indeterminate interpretations of ASC-H and LSIL,
H) and low-grade squamous intraepithelial lesion (LSIL) cannot exclude high-grade squamous intraepithelial lesion (LSIL-H).
• Considering the similar risks of cervical intraepithelial neoplasia grade
after the Bethesda System 2014 and to compare it with
2 or higher (CIN 2+) and CIN 3+ for dual ASC-H and LSIL (ASCHL) and
other indeterminate interpretations. ASC-H, having a separate category of ASCHL for reporting cervical
cytology appears to be redundant and should be studied further.
Methods: Rates of high-risk human papillomavirus • The CIN 2+ and the CIN 3+ rates for ASCHL were statistically similar
(HPV) positivity and histologic follow-up and the to those of LSIL-H and ASC-H and remained so, even when stratified by
proportion of women with high-grade squamous human papillomavirus test results.
intraepithelial lesion on histologic follow-up were
compared for the combined interpretation of ASC-H and
LSIL (ASCHL) and the categories of LSIL, cannot The interpretation of low-grade squamous intraepithelial
exclude high-grade squamous intraepithelial lesion lesion (LSIL), cannot exclude high-grade squamous
(LSIL-H) and ASC-H. intraepithelial lesion (HSIL), or LSIL-H, was not strictly
regarded as a distinct category in the Bethesda System
Results: The percentage of ASCHL HPV-positive cases 2001 for reporting cervicovaginal cytology.1 However,
(86.0%) was similar to that of LSIL-H but significantly its use gained the support of multiple studies, and it has
higher in comparison to that of ASC-H. The rates of cervical been used as a Papanicolaou (Pap) test interpretation
intraepithelial neoplasia grade 2 or higher (CIN 2+) and by several laboratories. The reported rates of cervical
CIN 3+ for ASCHL (29.6% and 3.6%, respectively) were intraepithelial neoplasia grade 2 or higher (CIN 2+) with
similar to those of LSIL-H and ASC-H. When stratified LSIL-H have ranged from 24% to 61%, falling mostly in
by HPV test results, the proportions of patients with CIN between those associated with LSIL and HSIL and akin
2+ and CIN 3+ remained statistically similar to those with to those observed with atypical squamous cells, cannot
ASCHL and with LSIL-H and ASC-H. exclude HSIL (ASC-H).2-15 These findings supported its
Conclusions: Considering the similar risks of CIN 2+ and usage as a separate category and its clinical management
CIN 3+ for ASCHL and ASC-H, having a separate similar to that of ASC-H.9,11,14
category of ASCHL for reporting cervical cytology The Bethesda System 2014 recommended that the
appears to be redundant. formal cervical cytology nomenclature should be 2-tiered,
© American Society for Clinical Pathology, 2020. All rights reserved. Am J Clin Pathol 2020;154:553-558 553
For permissions, please e-mail: journals.permissions@oup.com DOI: 10.1093/ajcp/aqaa069
Goyal et al / Dual Interpretation of ASC-H and LSIL
comprising LSIL and HSIL. It discouraged the use of an For all cases retrieved, the patient’s age, the results of
indeterminate category that could result in confusion re- concurrent HPV testing (if any), and the type and results of
garding clinical management. In addition, a dichotomous any cervical histologic follow-up (including cervical biopsies,
nomenclature was favored because it was in line with the endocervical curettages, loop electrosurgical excision pro-
Lower Anogenital Squamous Terminology (LAST) pro- cedures, cold knife cone biopsies, and hysterectomies) within
ject recommendations.16 The Bethesda System 2014 re- 12 months subsequent to the Pap test were obtained. When
commended that when the squamous intraepithelial lesion multiple biopsies or specimens were received, the most severe
cannot be accurately graded, an explanatory comment re- diagnosis was recorded. The Pap tests were interpreted by
garding the uncertainty of the grade may be appropriate. board-certified cytopathologists and the histology specimens
Alternatively, the interpretation of ASC-H in addition to by gynecologic pathologists in our department.
that of LSIL can be made. Such interpretations should be The rate of HPV positivity; the percentage of women with
used only in a minor proportion of cases.17 histologic follow-up; and, of those, the proportion with CIN
Our laboratory has used the category of LSIL-H for 2+ and CIN 3+ for the different categories were compared
more than a decade, but recently we transitioned to the use using the χ2 test and Fisher exact test. To compare the means, a
The patients with an ASCHL interpretation were with ASCHL, 78.9% with ASC-H, and 89.4% with HSIL.
younger than those with LSIL-H, ASC-H (for both The percentage of patients with ASCHL who received histo-
periods). and HSIL (for 2014-2015), with the differences logic follow-up within 1 year of the Pap test was not statisti-
being statistically significant (P = .0005 for ASCHL vs cally different from that of LSIL-H, ASC-H, or HSIL.
LSIL-H and P < .0001 for other comparisons). The age
of women with ASCHL was not statistically different Rate of CIN 2+
from those with HSIL for the period 2017-2018 (P = .06). The rate of CIN 2+ for ASCHL interpretations
(29.6%) was not statistically different from that for
HPV Testing LSIL-H (25.7%) or ASC-H (22.8% and 31.1%). The rate
A high percentage of women were tested for HPV of CIN 2+ for HSIL interpretations was 60.1% and 68.8%
at our institution for the interpretations included in this for the 2 study periods, respectively.
study. For 2014 and 2015, 75.0% of patients with LSIL-H,
84.0% of patients with ASC-H, and 69.5% of patients Rate of CIN 3+
❚Table 2❚
Comparison of HSIL Rates on Histologic Follow-up for ASCHL and Other Cytologic Categories
With CIN 2+ on Follow-up, P Value With CIN 3+ on Follow-up, P Value
Cytologic Interpretation No. (%) (for Rate of CIN 2+) No. (%) (for Rate of CIN 3+)
ASCHL 47/161 (29.1) — 6/161 (3.6) —
LSIL-H 67/262 (25.7) .41 6/262 (2.4) .55
ASC-H (2014-2015) 56/244 (22.8) .15 9/244 (3.6) 1
ASC-H (2017-2018) 56/177 (31.1) .75 12/177 (6.7) .23
HSIL (2014-2015) 148/246 (60.1) <.0001 43/246 (17.4) <.0001
HSIL (2017-2018) 124/180 (68.8) <.0001 39/180 (21.6) <.0001
ASC-H, atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion; ASCHL, atypical squamous cells, cannot exclude high-grade squamous
intraepithelial lesion, and low-grade squamous intraepithelial lesion; CIN 2+, cervical intraepithelial neoplasia grade 2 or higher; CIN 3+, cervical intraepithelial
neoplasia grade 3 or higher; HSIL, high-grade squamous intraepithelial lesion; LSIL, low-grade squamous intraepithelial lesion; LSIL-H, low-grade squamous
intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion.
ASCHL, atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion, and low-grade squamous intraepithelial lesion; CIN 2+, cervical
intraepithelial neoplasia grade 2 or higher; CIN 3+, cervical intraepithelial neoplasia grade 3 or higher; HPV, human papillomavirus; HSIL, high-grade squamous
intraepithelial lesion; LSIL-H, low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion.
❚Table 4❚
Comparison of HSIL Rates on Follow-up for ASCHL and ASC-H Categories (HPV-Positive and-Negative Segments)
Cytologic In- Cytologic In- P Value
terpretation terpretation P Value (ASCHL vs
Histologic Follow-up Stratified by Cytologic Interpreta- of ASC-H for of ASC-H for (ASCHL vs ASC-H ASC-H for
HPV status tion of ASCHL (%) 2014-2015 (%) 2017-2018 (%) for 2014-2015) 2017-2018)
HPV positive with CIN 2+ 32.7 41.9 42.9 .19 .13
HPV positive with CIN 3+ 3.8 6.4 9.7 .40 .06
HPV negative with CIN 2+ 6.2 6.8 9.3 1 1
HPV negative with CIN 3+ 0 1.2 1.7 1 1
ASC-H, atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion; ASCHL, atypical squamous cells, cannot exclude high-grade squamous
intraepithelial lesion, and low-grade squamous intraepithelial lesion; CIN 2+, cervical intraepithelial neoplasia grade 2 or higher; CIN 3+, cervical intraepithelial ne-
oplasia grade 3 or higher; HPV, human papillomavirus; HSIL, high-grade squamous intraepithelial lesion; LSIL-H, low-grade squamous intraepithelial lesion, cannot
exclude high-grade squamous intraepithelial lesion.
report cases with features in between those of LSIL and HSIL ratio of 1.17. In contrast, the dual interpretation
HSIL.18 Not only did the use of LSIL-H became widely of ASC-H and LSIL accounted for 0.3% of all Pap tests
prevalent, but it also increased. Walavalkar et al8 showed during the period of 2017 and 2018, with an ASCHL/HSIL
a statistically significant increase in the usage of this cat- ratio of 0.84. Neither the ASC-H rate (0.39% vs 0.35%)
egory at their institution, from 0.28% of total Pap tests nor the HSIL rate (0.36% vs. 0.31%) showed a significant
in 2005 to 0.61% in 2010. Their analysis also revealed an change after the incorporation of the ASCHL interpreta-
increase in the LSIL-H/HSIL ratio from earlier studies tion. These findings indicate that at least in the initial years
incorporating data from 2001 to 2003 to the later ones that of its implementation, the use of ASCHL has resulted in a
discussed findings from 2009 and 2010. Alsharif and col- decrease in such indeterminate interpretations.
leagues9 also noted in their study that LSIL-H accounted In terms of histologic follow-up, the average rate for
for 0.41% of Pap tests in 2007, having increased from 0.2% ASCHL (77.1%) was not significantly different from that
of Pap tests in 2004. Similarly, during 2014 and 2015, for ASC-H (78.9%), LSIL-H (77.2%), or HSIL (89.4%).
LSIL-H accounted for 0.43% of all Pap tests at our insti- This result indicates that at our institution, patients with
tution, exceeding the numbers of HSIL, with an LSIL-H/ ASCHL are being followed similarly to those with ASC-H
and the previously used categorization of LSIL-H. of abnormal cervical cancer screening tests aim for a
Other studies have reported varying rates of histologic simplified risk-based approach.20 Considering the similar
follow-up for ASC-H and LSIL-H. Nishino et al5 and rates of CIN 2+ and CIN 3+ in patients with ASC-H and
Owens et al13 reported high rates of histologic follow-up ASCHL in 1 year of follow-up in our study, one could
for LSIL-H (82.6% over 1 year and 71.7% over 2 years, argue that having a separate category of ASCHL appears
respectively), similar to our study. In contrast, other au- to be redundant. It creates confusion regarding the man-
thors have found much lower rates of histologic follow-up agement of the patient, and such cases could be incor-
for these categories. For instance, Elsheikh et al7 reported porated into ASC-H. However, we acknowledge that the
follow-up for 30.4% of LSIL-H interpretations; Thrall ASCHL category is HPV positive in a higher percentage
et al6 reported follow-up for 31.9% of LSIL-H and 35.3% of cases than is ASC-H. Studies with larger cohorts and
of ASC-H interpretations; and Alsharif et al9 reported longer follow-up duration can help elucidate whether
follow-up for 49% of LSIL-H and 56.7% of ASC-H inter- the risks of CIN 2+ and CIN 3+ significantly differ for
pretations. Such variations may be attributable, in part, to ASCHL (from those of ASC-H) for it to be regarded as a
differences in follow-up duration in the different studies distinctive cytologic category.
increase in CIN 2+ outcomes. Furthermore, our results 10. Barron S, Li Z, Austin RM, et al. Low-grade squamous
raise a question about whether ASCHL should be con- intraepithelial lesion/cannot exclude high-grade squa-
mous intraepithelial lesion (LSIL-H) is a unique category of
sidered separate from the Bethesda category of ASC-H.
cytologic abnormality associated with distinctive HPV and
Further studies will be helpful regarding the effects of histopathologic CIN 2+ detection rates. Am J Clin Pathol.
this practice modification to understand the impact of 2014;141:239-246.
the Bethesda System 2014 recommendations and its risk 11. Chiaffarano JM, Alexander M, Rogers R, et al. “Low-grade
squamous intraepithelial lesion, cannot exclude high-grade:”
of precancer to define management.
TBS says “Don’t use it!” Should I really stop it? Cytojournal.
2017;14:13.
12. Finkelstein A, Bajor-Dattilo EB, Yang MC, et al. The utility
Corresponding author: Abha Goyal, MD; abg9017@med.cornell. of “low-grade intraepithelial lesion, cannot exclude high
edu. grade” diagnosis: a single institution’s experience. Acta Cytol.
2012;56:383-387.
13. Owens CL, Moats DR, Burroughs FH, et al. “Low-grade squa-
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