Detection rates for abnormal cervical smears: what are we screening for?

We analysed rates of detection for smear abnormalities in 255,000 women served by the Bristol screening programme. The programme began in 1966 with the aim of eradicating the 30-40 deaths each year in Bristol from cervical cancer. Organisation has been good and population uptake has been high for the past 15 years. Records were computerised in 1977. During the 1988 to 1993 screening round, 225,974 women were tested. New smear abnormalities were found in 15,551, of whom nearly 6000 were referred for colposcopy. These numbers are excessively high in comparison with the incidence of the malignancy we are trying to prevent. The effect of screening on death rates in Bristol is too small to detect. Our conclusion is that despite good organisation of the service, much of our effort in Bristol is devoted to limiting the harm done to healthy women and to protecting our staff from litigation as cases of serious disease continue to occur. The real lesson from 30 years' cervical screening is that no matter how obvious the predicted benefit may seem for any screening test, introduction should never take place without adequate prior evaluation of both positive and negative effects in controlled trials.

Long term follow up of women with borderline cervical smear test results: effects of age and viral infection on progression to high grade dyskaryosis.

OBJECTIVE: To follow up and assess the significance of borderline change in cervical smears. DESIGN: Retrospective study of women undergoing routine cervical cytological screening in 1981. SETTING: Avon Cervical Screening Programme, covering 250,000 women in Bristol and Weston super Mare. SUBJECTS: 437 women showing borderline cervical changes in 1981 and 437 age matched controls with normal results in 1981. MAIN OUTCOME MEASURES: Cytological progression to high grade dyskaryosis (cervical intraepithelial neoplasia grade III or invasive carcinoma). RESULTS: During follow up ranging from 13 to 106 months 98 of the 437 women (22.4%) with borderline cytological changes on routine cervical cytology screening had a subsequent smear test showing high grade dyskaryosis compared with three of the 437 women (0.9%) in the control group. The risk of progression was greater in women aged 20 to 39 than in those aged 40 and over. Human papillomavirus infection had initially been diagnosed cytologically in 101 of the 437 (23%) women with borderline results. Significantly fewer of these women developed high grade dyskaryosis (13/98 (13%) v 88/339 (26%), p less than 0.05). CONCLUSIONS: Women with borderline smear test results are at increased risk of developing high grade dyskaryosis, particularly if the borderline changes occur without cytological features of human papillomavirus infection. Progression occurs within three years in 50% of cases, although a linearly increasing risk was sustained over the nine years of follow up and was greatest in women aged 20 to 39. Careful follow up of these women is indicated.

Transitional cell carcinoma: a case for collaboration.

Urine samples from the greatest proportion of the numerical workload of most clinical microbiology laboratories. During the screening by microscopy, atypical cells were detected which did not conform to the normal cellular morphology found in urinary deposits. These specimens were referred to the Department of Cytopathology for a second opinion. From these referrals a small but significant number of previously undiagnosed transitional cell carcinomas were detected.

Six years' audit of laboratory workload and rates of referral for colposcopy in a cervical screening programme in three districts.

OBJECTIVE: To determine laboratory workload and rates of referral for colposcopy in a three district cervical screening programme during 1983-9 to assess the feasibility of accommodating call up of all women at risk, recall at three year intervals (now five year intervals), and investigation of women with all degrees of abnormality. DESIGN: Analysis of computerised screening histories dating back to 1977 of women screened in the Avon cervical screening programme. SETTING: Three district health authorities covering the population of Bristol and Weston-super-Mare, comprising 800,000 people, of whom 250,000 were female residents aged 20 to 64. SUBJECTS: 196,977 Women aged 20 to 64 screened in cervical screening programme since 1983. RESULTS: Laboratory workload devoted to follow up of women with abnormalities increased sharply between 1987-8 and 1988-9, with increases of 54% (from 2075 to 3196) in the number of smears for follow up of severe dyskaryosis and invasive cancer, 40% (from 1925 to 2695) for mild and moderate dyskaryosis, and 49% (from 1793 to 2677) for borderline change. The increases were partly explained by the introduction in April 1988 of protocols for follow up and investigation based on guidance in an intercollegiate working party report. The proportion of women with mild and moderate dyskaryosis who were recommended for referral for colposcopy increased steadily from 9.9% in 1983-4 to 79.9% in 1988-9, and for borderline change the proportions were 3.5% and 13.6% respectively. Of all women tested in 1988-9, referral for colposcopy was recommended in 3%. CONCLUSIONS: The increase in laboratory follow up work identified, if it continued, could result in half of existing laboratory capacity in Avon being devoted to follow up work by 1993, with little prospect of maintaining call, recall, and quality control. Investigation of all women with minor cytological abnormalities is neither justifiable nor sustainable and will undermine the benefits of screening by increasing the rate of false positive results and the financial costs.

A study of the effect of introducing a restrictive cervical screening policy on laboratory workload and cervical cancer detection rates.

This study examines the effect of a change in screening policy on the detection rate of severe dyskaryosis. During 1987 a total of 423 cases of severe dyskaryosis were identified by the Avon Screening Programme. Eleven per cent of these abnormal smears were repeat smears taken without clinical indication within the recommended 5 year recall period (interval smears). In a comparable control group of negative smears 31% were interval smears. Twenty-five per cent of the dyskaryotic interval smears (3% of the total severely dyskaryotic smears) were taken within 3 years of the previous negative smear, compared with 50% of the control group. By discouraging opportunistic smears within 5 years of the previous smear, the laboratory workload could be reduced by 30%, or within 3 years of the previous smear by 15%. There is, however, a risk of 11% and 3% respectively of missing a significant lesion (severe dyskaryosis).

Management of women with abnormal cervical smears: supplement to terminology in gynaecological cytopathology.

Recommendations are made for the management of patients with abnormal cervical smears. Colposcopic examination is indicated for persistent mild and moderate dyskaryosis, as well as for severe dyskaryosis.

Terminology in gynaecological cytopathology: report of the Working Party of the British Society for Clinical Cytology.

The report defines and recommends terms for use in cervical cytology.

Prospective study of the human polyomaviruses BK and JC and cytomegalovirus in renal transplant recipients.

Forty eight renal transplant recipients were investigated prospectively for evidence of infection with the polyomaviruses BK and JC and cytomegalovirus. An active polyomavirus infection was shown in 31 patients (65%) and cytomegalovirus in 30 (62.5%). Half of the BK and JC virus infections occurred within the first three months after transplantation compared with 93% of the cytomegalovirus infections. Very late polyomavirus infections two or more years after the transplant were also shown. Cytology was useful in identifying polyomavirus but not cytomegalovirus infections, and 21 (68%) of the 31 polyomavirus infected patients excreted inclusion-bearing cells. Only three patients had symptoms possibly associated with the polyomavirus infection. One patient with BK virus infection developed ureteric stenosis and a second patient had malaise and vomiting. One patient with JC virus infection developed pericarditis and effusion. Renal function became impaired at the time of the polyomavius infection in eight patients (26%) and ureteric obstruction and pericarditis developed in two patients treated with methyl prednisolone for possible rejection. At the end of the study 25 of the 31 polyomavirus infected patients (81%) had functioning renal grafts. The detection of polyomavirus infection is important as increased immunosuppression needs to be avoided to prevent possible complications such as ureteric stenosis in transplant recipients.

Accuracy of oesophageal brush cytology: results of a prospective study and multicentre slide exchange.

The value of brush cytology has been assessed in the diagnosis of 101 oesophageal strictures in a department with no previous experience of oesophageal cytology. Cytological specimens obtained using a brush gave a correct diagnosis in 86 per cent of 36 malignant strictures with only 2 false negatives; when combined with biopsy, accuracy rose to 92 per cent. Of 65 benign strictures examined there were 3 false positives. In a series of test slides sent to 11 other hospitals the average false negative diagnosis was 4 per cent and false positive 3 per cent. Four of the centres had little previous experience and only two had extensive experience in oesophageal cytology. Therefore, brush cytology as a proved aid to the accurate diagnosis of oesophageal malignancy is within the capability of most pathology departments and should be used more widely.

Human polyomavirus (BK) infection and ureteric stenosis in renal allograft recipients.

Human polyomavirus (BK) was detected in two renal allograft recipients as a result of routine examination of Papanicolaou-stained smears of urinary sediment in the light microscope. Infection with this recently identified virus was confirmed by virus isolation and electron microscopy. The cytological, histological, and ultrastructural changes due to the virus are described, and virus excretion is correlated with the clinical progress of the patients and the pathological findings. The transplant ureters in both patients were found to be ulcerated and stenosed, and virus-infected cells were observed in the ureteric epithelium. We suggest that the administration of high-dose steroids in transplantation may permit active infection with human polyomavirus to occur in ureteric epithelium which has been damaged by ischaemia or inflammation.

Human polyoma virus (HPV)--a significant pathogen in renal transplantation.

Routine cytological screening of Papanicolaou-stained smears of the urinary sediment from 57 renal allografts in 51 patients has resulted in the detection of seven cases of Human Polyoma Virus (HPV) BK infection--14% of the total number. Infection was confirmed by virus isolation and electron microscopy (EM). The cytological, histological and ultra-structural data are described and related to the clinical progress of the patient. Four out of the seven cases are discussed in more detail as histological material was available; in three of these, there was evidence of stenosis of the transplant ureter with virus infected cells in the ureteric epithelium and in one case also in the renal tubules. Administration of high dose steroids may provoke active infection with HPV in ureteric epithelium damaged by ischaemia and inflammation. The similarity between the clinical features of an HPV infection and a rejection episode make it imperative to confirm the diagnosis quickly and accurately. Cytological examination of the urinary deposit by light microscopy is a simple, inexpensive procedure which provides positive diagnosis of the typical virus inclusions within an hour of receiving the urine specimen in the laboratory. This can be confirmed by removing single cells from the original cytological slide preparation and processing them for EM using a technique described by Coleman et al [1].