Abstract

To examine the diagnostic utility for squamous intraepithelial lesion (SIL) by cytological in situ hybridization (c-ISH) for the human papillomavirus using liquid-based cytology specimens, we investigated c-ISH signal patterns in the cases of low-grade SIL (LSIL), atypical squamous cells of undetermined significance (ASC-US), and high-grade SIL (HSIL). Episomal (E) and/or integrated (I) signals were observed. Two signal patterns (E≧I or I>E) were obtained by counting the number of E+ or I+ cells. E≧I was specific to LSIL and ASC-US (10/12); I>E, to HSIL (9/11) (P<0.01, χ2 test), suggesting significant utility of c-ISH in diagnosing SIL. In the cell fraction, E≧I in large cells was dominant in LSIL. Two cases of I>E in large cells of LSIL showed HPV persistence and/or progression during follow-up. Thus, c-ISH is useful in routine testing for diagnosing cervical dysplastic lesions, especially for detecting LSIL suspected for progression.

Highlights

  • Human papillomavirus (HPV) is responsible for uterine cervical cancer [1]

  • Cervical intraepithelial neoplasia (CIN) 1 lesions are regress spontaneously [4], it is known that high risk HPV integration occurs in a subset of low-grade squamous intraepithelial lesion (SIL) (LSIL) [5], which could be an early event in carcinogenesis

  • HPV DNA was detected in 27 patients by polymerase chain reaction (PCR) in negative for intraepithelial lesion (NILM) (2/3, 66.7%), LSIL (12/13, 92.3%), atypical squamous cells of undetermined significance (ASC-US) (2/5, 40.0%), and high-grade SIL (HSIL) (11/12, 91.7%)

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Summary

Introduction

Human papillomavirus (HPV) is responsible for uterine cervical cancer [1]. Screening programs for cervical cancer detection have greatly reduced the incidence of cervical cancer and cancer-related mortality. Evaluating exfoliated cells is more convenient than evaluating biopsy specimens for screening patients at high risk of cervical cancer. Cervical intraepithelial neoplasia (CIN) 1 lesions are regress spontaneously [4], it is known that high risk HPV integration occurs in a subset of LSILs [5], which could be an early event in carcinogenesis. It is important to detect a marker protein or viral genomic state (including the episomal [E] and/or integrated [I] form) before the lesion progress. Under these considerations, we evaluated cytological ISH (c-ISH) with LBC specimens by using a Ventana’s autostainer for detect the signal patterns and the results were evaluated along with the corresponding biopsy specimens

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