Follow-up Outcomes in a Large Cohort of Patients With Human Papillomavirus–Negative ASC-H Cervical Screening Test Results

Abstract

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.

Clinical Relevance of ASC-H Cytologies: Experience in a Single Tertiary Hospital

“…Some authors have concluded that a negative HPV test result accompanying ASC-H offers a high negative predictive value, and suggest the possibility of cytology and HPV testing at follow-up in low-risk patients instead of colposcopy. However, the results of other studies do not support these findings: some HPV-negative ASC-H cases end up being ≥CIN II lesions [4,11]. In a meta-analysis by Xu et al [18], the pooled absolute sensitivity and specificity of the hybrid capture 2 (HC2) for ≥CIN II (in 19 studies) were 93 and 45%, respectively.…”

“…Despite these, the majority of Pap smears can be assigned into specific categories [4]. ASC-H is an uncommon cytology interpretation with an estimated incidence of 0.27-0.56% [11]. The international recommendations indicate ASC-H cases should represent less than 10% of atypical cytologies.…”

“…The linear trend of correlation between ASC-US, ASC-H, and H-SIL and high-grade lesions in biopsy is mirrored in rates of HPV detection in these categories [16]. Moreover, immunohistochemical stains for p16 and Ki-67 are used electively and liberally by staff pathologists to increase the reliability of ≥CIN II diagnosis [11]. However, the utility of HPV testing as a primary tool to screen for cervical cancer and precancerous changes at baseline and follow-up is controversial.…”

“…Cohen et al [11] found that a previous history of ≥CIN II and/or multiple positive HPV test results identifies a group of patients at significantly increased risk for histopathological CIN II diagnoses compared with other patients with HPV-negative and ASC-US screening test results. Srodon et al [24] showed that patients with ASC-H had a twofold higher frequency of prior cervical abnormalities than patients with HPV-positive ASC-US, and a threefold greater frequency than patients with HPV-negative ASC-US.…”

Reflex Human Papillomavirus Test Results as an Option for the Management of Korean Women With Atypical Squamous Cells Cannot Exclude High-Grade Squamous Intraepithelial Lesion

“…Both the current ASCCP and Korean guidelines recommend initial colposcopy with biopsy for women with Papanicolaou test (Pap test) results showing ASC-H, regardless of the HPV test results; however, there have been ongoing debates about the clinical significance and utility of the HPV test for the management of ASC-H [12][13][14].…”