Evaluation of the PAPNET^™Cytologic Screening System for Quality Control of Cervical Smears

Abstract

The PAPNET system is an automated interactive instrument for analysis of conventional (Papanicolaou) cervical smears. The instrument, described in this paper, introduces several important innovations to cytology automation. The cell selection system is composed of two stages: an algorithmic classifier, followed by a trained neural network allowing for great flexibility and precision in recognition of abnormal cell images. Contrary to other attempts at cytology automation, this machine does not attempt to diagnose cell abnormalities. Instead, it is interactive, leaving the assessment of the cells displayed on a high-resolution video screen to trained human observers. The slides judged to contain abnormal cells or to be inadequate are referred for a second microscopic review. Two versions of the instrument (Alpha and Beta) were evaluated in several modes. Initial testing was performed on archival smears with known, histologically confirmed neoplastic lesions of the uterine cervix. These lesions comprised the entire spectrum of abnormalities, from low-grade lesions to invasive cancers of several types. The Alpha machine displayed recognizable abnormal cells in 97% of the 201 cases, and the Beta machine displayed such cells in 97.2% of 176 cases. The Beta instrument was subsequently tested on 500 sequential archival cervical smears that had been previously subjected to a rigorous quality control. One hundred forty smears (28%), which either displayed atypical cells or were considered "inadequate," were referred for further rescreening. Fifteen of 16 previously diagnosed neoplastic smears were appropriately identified with the help of the machine. The one missed case contained a single cluster of vacuolated cancer cells from an endometrial carcinoma. As a result of PAPNET-triggered review, three new cases of low-grade squamous intraepithelial lesions view, three new cases of low-grade squamous intraepithelial lesions (SIL) came to light in previously negative smears; three additional cases, previously classified as atypical, were also reclassified as SIL, for a net gain of six neoplastic abnormalities. In two additional atypical cases, colposcopic follow-up was recommended, even though the diagnosis was not modified. Two cases of cervical intraepithelial neoplasia, represented by tiny single clusters of abnormal cells missed on original screening, quality control, and on machine rescreening, came to light on second review of the residual 360 cases. The initial experience with the PAPNET system suggests that the instrument may be valuable in quality control and may assist in significantly reducing false-negative cervical smears in an efficient and timely manner. Further testing of the instrument on a much larger number of cervical smears is in progress.

Immunocytochemical detection of HPV16 E7 in cervical smear

“…The difficulty involved in identifying as few as a dozen abnormal/cancerous cells among 50,000 to 300,000 cervical cells, the large number of specimens that each trained cytotechnologist has to examine in a given time, and the sampling inadequacy are the factors associated with the problems. Recently, new technologies have contributed to improve the clinical sensitivity of the conventional Pap smear test by liquid-based preparation (Wilbur et al, 1994), pre-screening smears before a technologist's analysis (Wertlake, 1999), and confirmatory, reevaluation of a technologist's decisions (Koss et al, 1994). However, these modified Pap smear tests require elaborate apparatus and expensive reagents for routine operations.…”

Automation and the Endangered Future of the Pap Test

“…Early clinical trials (44,(46)(47)(48) provide convincing evidence that PapNet performs as expected. However, one of the difficulties in assessing the relevance of these clinical trials is the necessity to increase the percentage of abnormal cases required to determine the sensitivity of the system in a relatively short period.…”

A Semi - Automated Morphometric Assessment of Nuclei in Pap Smears Using Imagej

“…In developed world, large scale screening is done using one of the commercially available automated protocols viz, Pap Net, [5] BD Focal Point. [6] However, these are expensive and are not cost effective for low volume work.…”

“…[4] In fact, several commercial devices/protocols are available aimed at improving the quality of preparation of smears and its interpretation (Pap Net. [5] BD Focal Point. [6] ) However, these are expensive and are not suitable for small volume work.…”