Am J Clin Pathol 2012;138:517-523 517
517 DOI: 10.1309/AJCPYK60BZRNNAHQ 517
© American Society for Clinical Pathology
Anatomic Pathology / HPV-Negative ASC-H
Follow-up Outcomes in a Large Cohort of Patients With
Human Papillomavirus–Negative ASC-H Cervical Screening
David Cohen, MD, R. Marshall Austin, MD, PhD, Christopher Gilbert, MD, Richard Freij, MD,
and Chengquan Zhao, MD
Key Words: Cervical cytology; Atypical squamous cells, cannot exclude HSIL; ASC-H; Human papillomavirus; Follow-up results
A b s t r a c t
Limited follow-up data are available on patients
with cervical cytology results of atypical squamous
cells, cannot exclude a high-grade intraepithelial
lesion (ASC-H), who test negative for high-risk human
papillomavirus (hrHPV). Between June 2005 and
December 2010, 885 patients were identified with
ThinPrep results of Hybrid Capture 2 (HC2) hrHPV-
negative cervical ASC-H liquid-based cytology
and follow-up histopathology or cytology results
extending to September 2011. Of the 885 patients with
available follow-up results, 549 (62.0%) had at least
1 histopathologic result during the entire follow-up
period, whereas 336 (38.0%) had only cytologic
follow-up documented. In an average follow-up
period of 29 months, 14 (1.6%) of 885 patients with
HPV-negative ASC-H results showed evidence of high-
grade cervical intraepithelial neoplasia (CIN2/3). No
cases of invasive cervical cancer were diagnosed. Four
of 14 patients with HPV-negative ASC-H results with
follow-up diagnoses of CIN2/3 had a history of earlier
CIN2/3 diagnoses before HPV-negative ASC-H results.
Follow-up of patients with HPV-negative ASC-H
results using methods specified in this study yielded low
rates of detectible CIN2/3 and no diagnoses of cervical
cancer. Triage of study patients with HPV-negative
ASC-H results to routine HPV and cytology cotesting at
1 year was a safe follow-up option.
Atypical squamous cells, cannot exclude high-grade
intraepithelial lesion (ASC-H), is an uncommon cytology
interpretation with an estimated incidence of 0.27% to 0.56%
among the approximately 65 million Papanicolaou (Pap)
tests performed annually in the United States.1,2 A relatively
new classification, ASC-H is a subset of abnormal cytomor-
phologic changes formally introduced in the United States
in the 2001 Bethesda System (TBS2001).3 Early data on the
association of similar cytologic changes with histopathologic
high-grade cervical dysplasia came from several small stud-
ies reported before TBS2001.4,5 In the influential atypical
squamous cells of undetermined significance (ASCUS) low-
grade squamous intraepithelial lesions (LSIL) Triage Study
(ALTS), 110 women with retrospective panel interpretations
of ASC-H were reported to have an 84% rate of high-risk (hr)
HPV-positive results and a 58.7% rate for underlying histo-
pathologic cervical intraepithelial neoplasia (CIN) 2 or worse
(CIN2+) findings.6 This retrospective analysis of ALTS data,
involving a highly selected young patient population and an
internal consensus pathology review panel, served largely as
the basis for the 2006 American Society for Colposcopy and
Cervical Pathology (ASCCP) Guidelines suggesting universal
colposcopic referral for women with a Pap interpretation of
ASC-H without routine HPV testing.7 Since 2001, however,
the methods used in the United States for routine cervical
screening have changed significantly. Liquid-based cytology
(LBC), reflex hrHPV testing after ASC-US Pap results, com-
puter-assisted screening, and adjunctive hrHPV cotesting in
women aged 30 years and older have all become much more
common. Substantial additional data have accumulated on
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interpretation of ASC-H by retrospective analysis of the ASCUS-LSIL
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Am J Clin Pathol 2012;138:517-523 523
523 DOI: 10.1309/AJCPYK60BZRNNAHQ 523
© American Society for Clinical Pathology
Anatomic Pathology / Original Article
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