Management of women with mild and moderate cervical dyskaryosis.

OBJECTIVE--To compare the outcomes in women with mild and moderate dyskaryosis after increasing periods of surveillance and thereby to define a rational protocol for managing such women. DESIGN--Prospective study with randomisation of women to one of four treatment groups, each with a different period of surveillance; one group in which the women were given immediate treatment and three other groups in which the women were under surveillance for six, 12, and 24 months. SETTING--A dedicated colposcopy clinic in Aberdeen, Scotland. SUBJECTS--902 women who presented with a mildly or moderately dyskaryotic smear for the first time. INTERVENTIONS--Cytological and colposcopic examinations at intervals of six months until the allocated period of surveillance was completed, at which time biopsy was performed. Women with severe dyskaryosis were withdrawn from surveillance and a biopsy was performed. MAIN OUTCOME MEASURES--The histological findings after punch biopsy or large loop excision of the transformation zone, and the trends in cytological appearances of serial cervical smears. RESULTS--793 women completed the study. In all, 769 women had an adequate final smear, of which 197 were normal cytologically, 328 were still mildly or moderately dyskaryotic, and 244 were severely dyskaryotic. Seventeen of the 67 (25%) women with one repeat smear showing non-dyskaryosis had cervical intraepithelial neoplasia grade III compared with only one of the 31 (3%) women with no dyskaryosis in four repeat cervical smears (P < 0.0001). None of the women had invasive cancer. Of 158 women whose index smear showed mild dyskaryosis and who were allocated to the group under surveillance for two years, only 40 had not defaulted or still had dyskaryotic smears by the end of the two years. CONCLUSION--Cytological surveillance, although safe, is not an efficient strategy for managing women with mildly abnormal smears. Women with any degree of dyskaryosis in a smear should be referred for colposcopy.     

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.     

Colposcopy in a family planning clinic: a future model?

The first year''s experience of a satellite colposcopy clinic in the Glasgow Family Planning Centre was analysed. Establishment of the clinic was supervised by an experienced member of the colposcopy team at the department of gynaecology, Western Infirmary, Glasgow, who trained one of the family planning centre''s staff. Close links were thus maintained with the hospital clinic to which patients were referred for treatment. The policy at the new colposcopy clinic was to study prospectively all women in the hospital catchment area whose cervical smears were reported as abnormal. In 58 of 162 such patients there was at least moderate dyskaryosis and the cytologist''s recommendation had been referral for colposcopy. In 104 cases the changes were either atypia alone or mild dyskaryosis and a repeat smear was recommended within three to 12 months; 18 of these patients had grade II or III cervical intraepithelial neoplasia on biopsy, and relying on repeat smears would have resulted in an 11.7% false negative rate. If an atypical cytological picture is to be an indication for colposcopy clinics attached to family planning centres may have an important role, given satisfactory training and close links with central specialist colposcopy clinics.     

Management of Women With A Cervical Smear Showing A Mild Degree of Dyskaryosis: A Review of Policy

Three hundred and thirty-seven women who presented for the first time with a cervical smear showing a mild degree of dyskaryosis were followed for a minimum period of 3 years and 9 months. Of the 305 women with complete cytological and histological records, 178 were biopsied and 127 remained on cytological follow up. In the biopsied group one case of microinvasive squamous cell carcinoma was diagnosed within 1 year of the patient's first abnormal smear. A further 24% showed cervical intraepithelial neoplasia (CIN) I, 17% showed CIN II and 29% showed CIN III. The overall regression rate for the group of 305 women was 34%. Our results indicate that cytological surveillance is acceptable provided that biopsy is advised when dyskaryosis persists. No major modifications to laboratory policy are indicated and in approximately 34% of cases an unnecessary hospital referral would be avoided.     

Risk of cervical cancer associated with mild dyskaryosis.

In a survey of 1781 patients who had mild dyskaryosis in a cervical smear taken between 1965 and 1984 invasive cancer occurred in 10 women. In four cancer was diagnosed soon after presentation, and in three it developed some years after default from follow up. Invasion occurred in one patient during cytological surveillance and in a further two after referral for colposcopic supervision. A poor correlation was found between a single cervical smear showing mild dyskaryosis and biopsy results. This was, however, improved by a series of smears. During initial surveillance cervical smear results reverted to normal in 46% of our patients within two years. During longer term follow up none of these patients developed invasive cancer, and life table analysis showed that three quarters had not relapsed after 14 years. We also found no evidence to suggest that preinvasive disease is more rapidly progressive in younger women. Our results indicate that cytological surveillance is acceptably safe provided that biopsy is advised if dyskaryosis persists.     

Acceptability of the Cytopipette in General Hospitals

Altogether 2,798 cytopipette smears have been taken by patients entering the general medical and surgical wards of a hospital. Twelve unsuspected positive smears were found, a rate of 4 per 1,000. Biopsy of these patients has shown five pre-malignant lesions, one invasive carcinoma of cervix, and one carcinoma of corpus uteri. Five patients await biopsy.The cytopipette is both acceptable to the patient (62% acceptance) and a feasible laboratory technique and can produce good cytological smears. Only 30% of patients entering the hospital had already had the opportunity to obtain a smear before, and most of them welcomed the opportunity for the test.Though the self-pipette may be criticized for its inaccuracy we feel that any test, if it can detect cervical abnormality at the rate of 4 women per 1,000, is better than no test at all. It should have a place in routine cytological testing of women second only to the use of Ayre''s spatula.     

The Cardiff Cervical Cytology Study: prevalence of cytological grades and initial histological findings.

Among 45 266 women in the Cardiff Cervical Cytology Survey the peak prevalence of suspicious or positive smears was 11.2/1000 at age 45-50 years and of dyskaryosis 10.2/1000 at age 25-29. A suspicious or positive cytological picture at prevalence testing was associated with occult or clinical invasion in 24% of cases, and only 4% of patients with suspicious or positive smears were normal histologically. When dyskaryosis was detected in the prevalence test 20% had carcinoma in situ or microinvasion and 3% had occult or clinically invasive carcinoma. One hundred and twenty-nine (51%) women with dyskaryotic smears did not have a biopsy initially (that is, within two years of the prevalence test), but they were followed up at regular intervals. Subsequently 15 of the 129 gave smears consistently dyskaryotic or worse cytologically and were subjected to biopsy. Of these, two showed dysplasia, 12 carcinoma in situ, and one clinically invasive carcinoma. These findings emphasise the need for repeat cytological or histological examination in any woman with evidence of dyskaryosis in a cervical smear.     

Invasive cancer of the cervix in women with mild dyskaryosis followed up cytologically.

Mildly dyskaryotic smears are common, and women with such results are often followed up with further cervical smear tests. An important consideration in evaluating this practice would be the annual incidence of invasive cervical cancer. A reanalysis of five previous studies of the cytological follow up of women with mildly abnormal smear test results was undertaken to calculate this incidence. The annual incidence of invasive cancer in these women ranged from 0 to 420 per 100,000 women years. The large studies providing the most precise estimates had annual rates of 143 to 420 per 100,000 women years. This is 16 to 47 times greater than in women aged 15-34 years in England and Wales. The average rate was 208 per 100,000 women years. Women with mild dyskaryosis are at high risk of developing invasive cervical cancer despite cytological follow up. A full appraisal of the costs and benefits of colposcopy in this situation is urgently required.     

Quinquennial cervical smears: every woman's right and every general practitioner's responsibility.

Out of 558 women aged 16 to 64 who were registered with one general practitioner, 459 were eligible to be screened for cervical cancer. Even though the practice had been taking cervical smears for many years, they were predominantly from women under 35. Of the eligible women between 35 and 64, 111 (37%) had never had a smear. After short term intensive screening the uptake rates, defined by a smear done within the past five years, rose to 100% for women under 35, 94% for those aged 35 to 64, and 96% for all eligible women. Screening was rewarding both in its clinical yield and in the income generated by item of service payment. The success of screening was largely due to the participation of practice nurses in taking smears, and to a new method of recording smear results and claims for them. Some women, however, refused to have cervical smears.     

Outcome of women referred to colposcopy for persistently inadequate smears

The outcome of referral to colposcopy of 240 women who had persistently inadequate smears was investigated. Of 232 women who attended colposcopy, 214 (92.2%) had a normal outcome, 12 (5.2%) had low grade abnormalities, and six (2.6%) had high grade abnormalities. This group of women therefore has a negligibly increased risk of harbouring cervical neoplasia. Although not directly comparable, women with a history of previous abnormal cytology did not have a higher risk than those without such a history. Unnecessary colposcopy could have been avoided in the majority of cases if a good quality repeat smear had been taken. Improved smear taker training could decrease the number of referrals. A hospital cytology clinic is proposed as a cost-effective alternative to colposcopy at the first attendance.     

Rapid review in cervical cytology: a retrospective review of cases detected on rapid review within a DGH cytology department and subsequent outcome

We retrospectively reviewed smears detected by rapid review within a district general hospital (DGH) laboratory over a period of 33 months and the subsequent histological or cytological outcome. Sixty-three cases had adequate follow-up data: 32 subsequently had two negative smears and 31 had a histological abnormality on subsequent biopsy. Twenty were high-grade lesions (CIN2, CIN3 or a glandular lesion) and eight of these were preceded by a low-grade smear abnormality. We reviewed and compared the pattern and distribution of smear abnormalities in these 63 cases. Abnormalities were often present within few cells (76%, n = 48 with 50 abnormal cells or less) or in micro-biopsies (27%, n = 17). There was no statistical difference in the pattern and distribution of smear abnormality between the rapid review-detected smears with a biopsy-proven abnormality and those with negative follow-up smears. Overall, the positive predictive value for high-grade CIN detected by rapid review (75%) was within NHSCSP achievable standards targets. This review of rapid review-detected abnormalities and the biopsy and cytological follow-up reiterates the importance of the method in cervical screening.     

Preliminary results of a district call scheme for cervical screening organised in general practice.

A recognised problem with the cervical screening programme in the United Kingdom is the failure to include women who have never had a cervical smear test, who are a high risk group. The implementation of a district based call scheme in East Berkshire in 1986 is described whereby women aged 20-64 with no record of a cervical smear test who were judged to be eligible for testing by their general practitioner were sent a personal invitation from their general practitioner to attend for a test. A list of high risk unscreened women was kept by each practice, and a duplicate sent to the cytology laboratory to update the central records. Six months after each batch of invitations had been sent the resulting number of women having a smear test was assessed. Forty three of 51 practices approached agreed to participate in the five year scheme. During the first year lists were sent to the 43 participating practices. The first list was returned to the cytology laboratory by 37 practices and the second by 33; practices varied in their responses, however, some needing considerable persuasion to return the lists. Of 972 identified unscreened women from the total 3757 women listed in the lists of the family practitioner committee, 247 (25%) had a cervical smear test in response to the invitation, representing an overall increase of 7% in the screened population. The preliminary findings of the five year study have shown that screening can be improved by a systematic call scheme. Coordinated support from the area health authority in health education, monitoring of screening, and feedback of data from the scheme to practices is required to reduce the proportion of unscreened women.     

Prevalence of cervical pathogens in women with and without inflammatory changes on smear testing.

OBJECTIVE--To assess correlation between nonspecific cervicitis, inflammation, or exudate on cervical smears tests and confirmed presence of known cervical pathogens. DESIGN--Investigation of women attending a family practice clinic for smear test by microbiological screening for Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Trichomonas vaginalis, Candida species, group B streptococcus, Gardnerella vaginalis, and Neisseria gonorrhoeae. SETTING--Family practice teaching clinic in a university hospital. PATIENTS--411 women presenting for a smear test. MAIN OUTCOME MEASURES--Prevalence of genital infections associated with presence or absence of inflammatory changes on cervical smear. RESULTS--Of the 132 women with inflammatory changes on cervical smear, 64 (48%) had positive cultures. Of the 248 without inflammatory changes, 117 (47%) had positive cultures. Subgroup analysis on individual organisms also showed no significant difference between the two groups. CONCLUSION--Reports of inflammatory changes on cervical smear testing are a poor indicator of infection.     

Are patients with abnormal cervical smears adequately managed?

The outcome was assessed for all 1062 women in Nottingham who had a first report of abnormal cervical cytology in 1981. Satisfactory follow up could be found for only 628 (59%) of them. For 275 (26%) one subsequent normal smear had been reported but no further follow up requested. For 43 (4%), no subsequent test, after the abnormal smear, had been requested by the patient''s general practitioner. Thirty patients (3%), 22 of whom had been tested at a special clinic, had not responded to a request for follow up. Even after extensive efforts we could not find the outcome in the remaining 86 (8%) of the patients. Adequate follow up of patients with abnormal cervical cytology is not being achieved. Improvements in the records systems and some changes in procedure should be made to reduce this problem.     

P‐26CONVENTIONAL V THIN LAYER TECHNIQUES: A COMPARATIVE STUDY OF BRONCHIAL SPECIMENS USING CONVENTIONAL AND TWO LBC METHODS,THINPREP AND SUREPATH

Introduction: There is ongoing debate about the terminology used in the classification of dyskaryosis, including whether BNA smears should be classified according to whether koilocytes are present or not. We explored the effect of koilocytosis in the management experiences and clinical outcomes of women with a single BNA smear. Methods: This study includes 410 women aged 20–59 years, resident in Tayside who had an ‘baseline’ BNA smear between 31/10/1999 and 31/10/2002 who were eligible for the TOMBOLA trial but who did not participate. Recommended follow‐up for these women was a repeat smear in six months. Up to three‐years follow‐up data was collected on subsequent cytological smears, colposcopy examinations and any related histology. The baseline smear was re‐read for the presence or absence of koilocytes. Women were classified according to their clinical outcomes during their three years. Results: 47% (192/410) of women were classified as having koilocytosis at baseline. The mean age was lower among these women (25 years) compared to those without koilocytosis (35 years). 55% (105/192) of women with koilocytosis at baseline had one or more negative smears and no further abnormal smears, compared to 63% (137/218) of those without koilocytosis, the difference was not statistically significant. 28% (53/192) of women with koilocytosis at baseline were referred to colposcopy after subsequent low‐grade or high‐grade smears compared to 19% (42/218) of those without koilocytosis; the difference was statistically significant. 14% (27/192) of women with koilocytosis at baseline were diagnosed with CIN2/3 or worse during follow‐up compared to 10% (21/218) of women without koilocytosis; the difference was not statistically significant. Discussion: Our results suggest that the presence or absence of koilocytosis has little impact on the clinical outcomes of women with a BNA smear.     

Review of cervical smears from 76 women with invasive cervical cancer: cytological findings and medicolegal implications

OBJECTIVE: To review cervical smears from 76 women which were taken prior to the diagnosis of invasive cervical cancer and to determine the appropriateness of the cytology reports issued on the smears. METHODS: Cervical smears, clinical records, cervical smear history and cytology reports from 76 women with invasive cervical cancer were reviewed. After microscopic review of the cervical smears, the cases were divided into two groups: Group 1 comprised 50 women who were found to have had at least one false-negative (F/N) smear report prior to the diagnosis of invasive cervical cancer. Group 2 comprised 26 women for whom no evidence of F/N reporting was found. RESULTS: A total of 209 cervical smears from the 50 women in group 1 were available for review (range 2-12 smears per woman); 100 of the 209 smears were considered to have been reported appropriately. Ninety-seven smears which had been reported originally as negative or inadequate were found, on review, to contain numerous severely dyskaryotic cells and were reclassified as F/N smears. All of the 50 women had at least one F/N smear and 29 had two or more. Twelve smears from eight women contained only a few (<200 severely dyskaryotic cells). Forty women developed invasive squamous carcinoma and 10 developed invasive adenocarcinoma. The stage at diagnosis ranged from 1A to stage 4. Seventy-one smears from the 24 women in group 2 were available for review (range 1-15 smears per woman). In two cases included in group 2, no smears were provided for review as the smears had been lost or mislaid. Review of the 71 smears confirmed the accuracy of the original cytological classification of the smear. Nineteen women were diagnosed with squamous cancer, two microinvasive cancer, one glassy cell, two adenocarcinomas, and one with adenosquamous carcinoma. One women was found to have an embryonal rhabdomyosarcoma of the corpus uteri involving the cervix. DISCUSSION/CONCLUSION: The medicolegal implications are discussed in the light of the above findings. Evidence of breach of duty of care was presented in all 50 cases in group I although causation was not established in every case. There was no evidence of failure of duty of care in terms of the standard of the cervical cytology reports issued or standard of clinical management in 17 of the 26 cases in group 2. However, in seven of the 26 cases in group 2, clinical management of the case was substandard due to failure to investigate symptoms of irregular bleeding regardless of a negative cytology report (two cases), failure to act upon a suspicious smear report or consecutive inadequate smear reports (two cases), failure of follow-up after treatment of CIN3 (two cases) and histological misdiagnosis (one case).     

Outcome analysis of 4 years' follow-up of patients referred for colposcopy with one smear showing mild dyskaryosis

Objective: To assess the 4‐year outcome of patients after one smear showing mild dyskaryosis with respect to smear regression rate, prevalence of cervical intraepithelial neoplasia (CIN) and the effect of age. Methods: Retrospective analysis of patients diagnosed with initial mildly dyskaryotic smear during the year 2000 with a follow‐up period of 48 months. These women had not had any previous abnormal smears. Settings: Cytopathology Department and Colposcopy Unit, King’s College Hospital, London, UK. Results: We identified 524 patients of whom 375 patients with complete follow‐up data are included. The age range was 19–67 years with a median of 29 years. There were 207 patients aged 35 years or less (55%). At 6 months, 258 smears were performed and 47.8% of them were negative (95% CI: 41.6–54.0%). The total number of negative follow‐up smears in the first year was 198 out of a total of 397 smears performed (50%). This proportion has significantly increased between 1 and 4 years’ follow‐up to 67.5% (RR: 1.24; 95% CI: 1.14–1.35). Over the 4‐year period, 791 smears were performed and 477 were negative (60.3%; 95% CI: 56.9–63.7%). Of the 477 negative smears there were only 61 smears (12.8%; 95% CI: 10–16%), in 54 patients (14%; 95% CI: 11–18%) that reverted back to low‐grade cytological abnormality. In only one case the repeat smear showed high‐grade abnormality after initial negative follow‐up; however, on biopsy, histology showed CIN I. Out of the 375 patients, 70 required treatment with excisional biopsy (19%; 95% CI: 15.0–22.9%). Histology confirmed high‐grade CIN in only 41 cases giving a prevalence of 11% (95% CI: 8.1–14.5%). There were no cases of microinvasive or invasive cancer detected. Age (≤35 years versus >35 years) did not significantly affect either cytological or histological outcome. Conclusion: Sixty per cent of follow‐up smears after initial mild dyskaryosis subsequently became negative; of them 87.2% remained negative over the 4 year follow‐up. Treatment was only required in 19% of patients, with 11% prevalence of high‐grade CIN. Age did not affect the outcome. These results are reassuring and indicate that colposcopic referral may not be necessary after only one mildly dyskaryotic smear.     

Relationship between the diagnosis of epithelial abnormalities and the composition of cervical smears

The significance of endocervical columnar cells as a high-quality parameter of cervical smears was studied. In a cohort of women with two successive screenings, the consistency of the cellular composition of the cervical smears and the relation between the cellular composition of the smears and the frequency of the diagnosis of abnormal epithelial changes was investigated. At the first screening, a significantly higher number of epithelial abnormalities was found in smears with endocervical columnar cells than in smears without endocervical columnar cells. A significantly higher number of abnormal epithelial changes was found on the second screening in smears from women whose smears from the first screening did not contain endocervical columnar cells than in smears from women whose smears from the first screening did contain endocervical columnar cells. The presence of endocervical cells should be considered a very important indicator of the quality of cervical smears. The chance of missing an abnormal epithelial change is increased in smears without endocervical columnar cells. When endocervical columnar cells are absent, the smear should be considered to be of unreliable quality and a repeat smear should be taken after a short interval, unless the absence of columnar cells can be satisfactorily explained.     

Screening for cervical cancer: a new scope for general practitioners? Results of the first year of colposcopy in general practice.

A survey was carried out over one year of all the women who attended a colposcopy clinic in a general practice. During the year 1254 women underwent cytological screening in the practice and 197 of these underwent colposcopy. Of 79 women with abnormal smears that suggested cervical intraepithelial neoplasia, 62 (79%) were confirmed by biopsy to have cervical premalignancy. In addition, the remaining 118 women with normal or inflammatory smears underwent colposcopy either because of their history or because they requested the investigation. A general underestimate of cervical intraepithelial neoplasia when cytology alone was used was discovered. Seven out of 28 women with inflammatory smears were found to have important cervical premalignancy. Mildly dyskaryotic smears led to a falsely reassuring estimate of the degree of severity of cervical lesions. Seven out of 13 patients who underwent colposcopy because they were thought to be at high risk of neoplasia because of a history of genital warts, unexplained recurrent cystitis, heroin abuse, or immunosuppression had cervical intraepithelial neoplasia proved at biopsy. This report shows that both in screening for and in the follow up of known cervical disease a normal smear cannot guarantee normal pathology. Diagnostic colposcopy is a valuable complementary investigation that could be carried out in a general practice.     

P-27ATYPICAL GLANDULAR CELLS ON SMEAR – AGE RELATED IMPLICATIONS AND MANAGEMENT

Introduction:  There is ongoing debate about the terminology used in the classification of dyskaryosis, including whether BNA smears should be classified according to whether koilocytes are present or not. We explored the effect of koilocytosis in the management experiences and clinical outcomes of women with a single BNA smear.
Methods:  This study includes 410 women aged 20–59 years, resident in Tayside who had an 'baseline' BNA smear between 31/10/1999 and 31/10/2002 who were eligible for the TOMBOLA trial but who did not participate. Recommended follow-up for these women was a repeat smear in six months. Up to three-years follow-up data was collected on subsequent cytological smears, colposcopy examinations and any related histology. The baseline smear was re-read for the presence or absence of koilocytes. Women were classified according to their clinical outcomes during their three years.
Results:  47% (192/410) of women were classified as having koilocytosis at baseline. The mean age was lower among these women (25 years) compared to those without koilocytosis (35 years). 55% (105/192) of women with koilocytosis at baseline had one or more negative smears and no further abnormal smears, compared to 63% (137/218) of those without koilocytosis, the difference was not statistically significant. 28% (53/192) of women with koilocytosis at baseline were referred to colposcopy after subsequent low-grade or high-grade smears compared to 19% (42/218) of those without koilocytosis; the difference was statistically significant. 14% (27/192) of women with koilocytosis at baseline were diagnosed with CIN2/3 or worse during follow-up compared to 10% (21/218) of women without koilocytosis; the difference was not statistically significant.
Discussion:  Our results suggest that the presence or absence of koilocytosis has little impact on the clinical outcomes of women with a BNA smear.