DNA image cytometry and human papillomavirus (HPV) detection help to select smears at high risk of high-grade cervical lesions

Abstract

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.

Detection of Genomic Amplification of the Human Telomerase Gene (TERC) in Cytologic Specimens as a Genetic Test for the Diagnosis of Cervical Dysplasia

“…This suggests that detection of 3q gain could be more sensitive than measurement of the nuclear DNA content alone. 10,37,38 The interpretation of the hybridization patterns provides evidence that chromosomal instability, measured in this study as the variability of hybridization patterns among cells in a given case, increases with the grade of dysplasia as well. This suggests that early chromosomal aneuploidies can develop in an otherwise genomically stable nucleus, and that the acquisition of specific chromosomal imbalances (in cervical carcinomas the gain of 3q) coincides with the HPV-mediated compromise of TP53 and RB1 function to promote tumorigenesis and eventually the acquisition of crude nuclear aneuploidy that is present in most invasive cervical carcinomas.…”

DNA Ploidy Cytometry Testing for Cervical Cancer Screening in China (DNACIC Trial): a Prospective Randomized, Controlled Trial

“…It is well known that cervical lesions in which cells have an aneuploid DNA profile are more likely to persist or progress than those with diploid or polyploid profiles (17)(18)(19)(20). Lorenzato and colleagues (21) reported that flow cytometric DNA ploidy measurement on conventional cervical smears positive for HPV could help detect women at high risk of cervical cancer. To our knowledge, there is limited data on DNA cytometry testing as a stand-alone screening test…”

Contribution of DNA ploidy image cytometry to the management of ASC cervical lesions

“…10,27,28 Since 2001, the International Consensus Conference on the Fight Against Cervical Cancer International Academy of Cytology (IAC) has recommended DNA image cytometry as a useful adjunct method for identifying cervical intraepithelial lesions with a high risk of progression.…”

“…These abnormalities are linked to or are the consequence of chromosomal instability induced by the presence of HR-HPV, and are associated with DNA ploidy disturbances. 7,[8][9][10][11] DNA aneuploidy indicates a potential neoplastic development toward cervical dysplasia. 9,12,13 Several mechanisms for DNA ploidy abnormalities in cervical lesions have been described, in particular the HR-HPV E7 oncoprotein expression, which blocks cell differentiation and induces DNA synthesis 14 by interacting with tumor suppressor pRB.…”