BACKGROUND. The Bethesda system classifies smears that suggest an underlying cervical intraepithelial neoplasia (CIN) as ASC (atypical squamous cell) smears. ASC smears are subdivided into ASCUS (of undetermined significance) and ASCH (cannot exclude a high‐grade lesion). Today the management of ASCUS is a triage with HR‐HPV testing and colposcopy is recommended for ASCH. The aim was to conduct a study on ASC smears to determine DNA ploidy measurement for the detection of CIN2+. METHODS. The link between a suspect DNA ploidy assessed by image cytometry and/or a positive HR‐HPV testing was analyzed on 69 ASCUS and 82 ASCH smears, and the presence of CIN2+ within 12 months after ASC diagnosis. The ploidy was suspect in case of aneuploidy, multiploidy, or in the presence of cells with a DNA content >5c or >9c. RESULTS. Every woman who had a CIN2+ had a suspect DNA profile in the ASCUS smears and every woman except 1 was HR‐HPV‐positive. The link between a positive HR‐HPV test or a suspect DNA profile or both and a CIN2+ was high (P = .019, .023, and .008, respectively). The presence of >9c cells was particularly linked to CIN2+ (P = .0031). In all, 90.9% and 87.9% of the ASCH smears with CIN2+ were, respectively, HR‐HPV positive or had a suspect ploidy (P = .0000 and P = .0043), and the presence of >9c cells was also linked to CIN2+ (P = .003). CONCLUSIONS. HR‐HPV testing and determination of the ploidy profile with special attention to 9c‐exceeding cells could be accurate for a better management of ASC smears. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.

Three samples were submitted from women undergoing routine screening (n=910): two smears (one for routine cytology and one for DNA image cytometry) and a scrape for human papillomavirus (HPV) testing. DNA histograms were classified as suspect in cases of aneuploidy, polyploidy, and/or diploidy with a high proliferation rate. Follow-up was available in 239 cases. The primary end-point was the presence of a high-grade squamous intraepithelial lesion (HGSIL) at biopsy. Seventy women (7.7%) had a high-risk (HR) HPV infection and a suspect DNA profile. In 77 women with cytological abnormalities, 28 HGSILs were detected: four with a prior diagnosis of ASCUS (all HR-HPV infected including three with a suspect DNA profile), three with smears evocative of LGSIL (all with HR-HPV infection and a suspect DNA profile), and 21 with smears evocative of HGSIL (all with HR-HPV infection and 20 with a suspect DNA profile). During the follow-up period, out of 239 women with a cytologically normal smear at first entry, five developed a HGSIL; all were HR-HPV-positive and four had a suspect DNA profile at the first smear. HR-HPV detection alone gives a sensitivity of 100% for the detection of HGSIL, with a specificity of 84.3%, whereas DNA measurement associated with HPV testing significantly enhances the specificity to 95.4%. Thus, the combination of HPV testing and DNA measurement provides a highly sensitive and specific evaluation of the risk of HGSIL on cervical smears.

To improve the positive predictive value (PPV) for high-risk human papillomavirus (HR-HPV) in primary screening, DNA ploidy was measured on the same liquid-based sample by image cytometry in 984 cases showing discrepancies between cytology and HR-HPV testing. Of the conflicting results, 14.5% corresponded to a cytologic lesion (from atypical squamous cells of undetermined significance to high-grade squamous intraepithelial lesion [HSIL]) without HPV detected, and 85.5% of smears were within normal limits but revealed an HR-HPV infection. A suspect DNA profile was associated significantly with a lesion. In 497 patients who underwent repeated HPV testing, a normal DNA profile at the first smear predicted the clearance of HPV infection (sensitivity, 81.5%; specificity, 45.4%; PPV, 69%; negative predictive value, 62.4%). In persistent HR-HPV infection, a suspect DNA profile at the first smear increased the PPVfrom 10.8% to 22.7% for the detection of a histologically proven HSIL with a sensitivity of 95.2%. DNA ploidy can be used to select smears with high risk of HSIL, especially in cases of persistent HR-HPV infection.

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