Regular audit of colposcopic biopsies from women with a mildly dyskaryotic or borderline cervical smear results in fewer cases of CINIII

Two years after introducing mandatory review of cases in which the cervical smear was discrepant with subsequent colposcopic or histological finding, the predictive accuracy of a first abnormal smear and the need for treatment were analysed. The results were compared with performance figures prior to this form of audit policy. Over 12 months 415 women referred for colposcopy were studied. Three per cent of patients with a single borderline smear and 6% with mild dyskaryosis had cervical intraepithelial neoplasia grade III (CINIII) revealed in histopathological examinations after colposcopy. Only 25% with a borderline smear and 33% with mild dyskaryosis required treatment. Of women with moderate dyskaryosis, 18% had a biopsy showing CINIII and 46% were treated. Of women with severe dyskaryosis in their cervical smear, 61% were shown to have CINIII or invasive cancer on biopsy and 90% were treated. Regular audit improved cytological prediction of grade of epithelial abnormality found on biopsy, allowing accurate, safe surveillance for minor smear abnormalities.     

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 Women with severe dyskaryosis were withdrawn from surveillance and a biopsy was performed.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.     

Koilocytosis; an indication for conservative management

The management of women with mild dyskaryosis continues to be the subject of debate. The management of cases with such smears could be improved if additional morphological features were found to be indicative of low/high grade cervical intraepithelial neoplasia (CIN). Our own experience in the routine audit of the diagnostic accuracy of cervical smears had suggested that cases of dyskaryosis with koilocytosis were associated with a low risk of CINIII. Two hundred and forty-four cervical smears reported as showing evidence of wart virus infection were reviewed and their subsequent histories noted. Of these smears, 173 demonstrated clear evidence of koilocytosis. Irrespective of the initial grade of dyskaryosis, only 28 cases (16.2%) had underlying CIN or had progressed to CIN over a minimum follow-up period of 21 months. Only two cases (1.2%) showed evidence of CINIII. Koilocytosis is associated with a low risk of CIN and an especially low risk of CINIII. The management of women with koilocytic smears should be modified accordingly.     

Koilocytosis; an indication for conservative management

The management of women with mild dyskaryosis continues to be the subject of debate. The management of cases with such smears could be improved if additional morphological features were found to be indicative of low/high grade cervical intraepithelial neoplasia (CIN). Our own experience in the routine audit of the diagnostic accuracy of cervical smears had suggested that cases of dyskaryosis with koilocytosis were associated with a low risk of CINIII. Two hundred and forty-four cervical smears reported as showing evidence of wart virus infection were reviewed and their subsequent histories noted. Of these smears, 173 demonstrated clear evidence of koilocytosis. Irrespective of the initial grade of dyskaryosis, only 28 cases (16.2%) had underlying CIN or had progressed to CIN over a minimum follow-up period of 21 months. Only two cases (1.2%) showed evidence of CINIII. Koilocytosis is associated with a low risk of CIN and an especially low risk of CINIII. The management of women with koilocytic smears should be modified accordingly.     

Mild and moderate dyskaryosis: can women be selected for colposcopy on the basis of social criteria?

OBJECTIVE--To describe the distribution of cervical intraepithelial neoplasia grades among women with mild and moderate dyskaryosis after a single cervical smear and to determine whether social criteria could help identify women who are at increased risk of grade II or III disease. DESIGN--Cross sectional analysis within a randomised prospective study. Subjects had a repeat smear, a colposcopic examination, and an excision biopsy of the transformation zone. In addition, women were asked to complete a social questionnaire. SETTING--Colposcopy clinic, Aberdeen. SUBJECTS--228 women with a single smear test showing mild or moderate dyskaryosis. MAIN OUTCOME MEASURES--Histology, age, sexual and contraceptive history, cigarette smoking. RESULTS--159 (70%) women had cervical intraepithelial neoplasia grades II or III. Among current smokers the prevalence of grade II and III disease was higher in women who smoked greater than or equal to 20 cigarettes a day (84%) than among those who smoked less (66%; p less than 0.04). Women with more than one sexual partner also had a higher prevalence (75%) than women with only one partner (50%; p = 0.0028). Use of oral contraceptives and younger age were not significantly associated. The prevalence of grade II or III disease was up to 66% in the lower risk groups. CONCLUSIONS--Because of the high prevalence of cervical intraepithelial neoplasia grades II and III in both the high and the low risk groups social factors are not useful for selecting women with mild or moderate dyskaryosis for either early referral to colposcopy or cytological surveillance.     

The Cytological Prediction of Cervical Intraepithelial Neoplasia In Colposcopically Directed Biopsies

The tissue sections and preceding cervical smears of 1262 women who had colposcopic cervical biopsies were reviewed and the reports correlated. Close correlation between the cytological and histological findings, to within one histological grade of cervical intraepithelial neoplasia (CIN), was noted in 86% of cases. However, the biopsy was negative, or contained evidence of wart virus infection only, in 24% of cases where dyskaryotic cells had been observed in the cervical smear. Of particular concern was the fact that negative histological findings were recorded in 13% of cases where the smear contained cells showing a moderate dyskaryosis and in 1.26% of cases where the smear showed severe dyskaryosis. This suggests that colposcopically directed biopsies do not always reflect the underlying pathological changes in the cervix. Management of these cases is discussed. In 45 women with a normal cervical smear prior to biopsy, histology revealed seven cases of CIN 3 and one case of invasive squamous carcinoma. This indicates that referral for colposcopy is advisable whenever there is clinical suspicion of cancer, even if the cervical smear report is normal.     

Five-year follow-up of women with borderline and mildly dyskaryotic cervical smears

This study investigated the 5-year follow-up status of women with cervical smears showing borderline nuclear changes (BNC) or mild dyskaryosis and the effect of koilocytosis on the outcome. Thirteen per cent of women with cervical smears showing BNC had high-grade cervical intraepithelial neoplasia (CIN). In contrast, 28% of women with cervical smears showing mild dyskaryosis had high-grade CIN. The presence of koilocytosis (24% for borderline smears and 34% for mild dyskaryotic smears) did not appear to influence the risk of developing high-grade CIN. Our results suggest that the simultaneous implementation of the British Society for Clinical Cytology proposed terminology and the colposcopy guidelines from the British Society for Colposcopy and Cervical Pathology could have an impact on colposcopy services.     

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.     

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.     

Assessment of the Accuracy of Cytology In Women Referred For Colposcopy and Biopsy: the Results of a 1 Year Audit

The results of weekly colposcopy review meetings have been audited for 1 year and cases where there was a discrepancy between the referral cervical smear and the initial colposcopy biopsy have been analysed. New referrals (n = 476) for colposcopy were studied. In the final outcome 80% of 326 women referred for moderate or severe dyskaryosis were found to have cervical intraepithelial neoplasia (CIN) grade II or III or invasive carcinoma. Three women found to have invasive carcinoma had been referred for severely dyskaryotic smears. Twenty women were referred for smears with cell changes suggesting glandular neoplasia: five were found to have adenocarcinoma in situ, whereas eight had CIN and seven had negative biopsies. The results justify the referral policy and demonstrate the need for further investigation when initial colposcopic biopsies are negative.     

An alternative approach to the management dilemma of the mildly dyskaryotic smear based on audit of outcome

We describe a study which takes an alternative approach to the management dilemma of the mildly dyskaryotic cervical smear. Two hundred and fifty women with a smear showing mild dyskaryosis were studied by auditing the clinical outcome as well as the cost. The cost of providing the colposcopy services during the index year was approximately pounds sterling 70000 for an average size district general Hospital. The proportion of women managed by the current guidelines and avoiding colposcopy after a first mildly dyskaryotic smear was only 30%. The majority of patients will eventually have colposcopy despite a policy of cytological surveillance. The alternative approach, to offer colposcopy immediately after the first mildly dyskaryotic smear, would result in a small increase in cost for our unit, equivalent to one extra colposcopy patient per week.     

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.     

Diagnosis and treatment of cervical intraepithelial neoplasia in general practice.

OBJECTIVE--To audit the first five years of a colposcopy and treatment service for cervical dysplasia established within a general practice. DESIGN--A cervical smear register was established to determine which women were "at risk" of dysplasia. The results of colposcopy and treatment of dysplasia were analysed. SETTING--A large rural general practice with community hospital facilities in mid-Wales. PATIENTS--4437 Women at risk in a total practice population of 14,100. INTERVENTIONS--Colposcopy of women with dyskaryotic smear results, persistent inflammatory smear results, or vulval warts. Treatment of women with proved dysplasia by electrodiathermy of the cervix or cone biopsy. RESULTS--138 Women with dysplasia were diagnosed over five years: 36 mild, 97 moderate or severe, and five with microinvasion. Despite a 78% smear rate of at risk women over five years, nine invasive cancers still occurred. CONCLUSIONS--The results of treatment are acceptable. Cervical dysplasia has become very common, the risk of a dysplasia in women aged 20-39 who had smear tests being one in 14 over five years.     

Borderline nuclear change,high‐grade dyskaryosis not excluded: current concepts and impact on clinical practice

S. S. Hoo, A. Patel, H. Buist, K. Galaal, J. D. Hemming and R. Naik Borderline nuclear change, high‐grade dyskaryosis not excluded: current concepts and impact on clinical practice Objective: Borderline nuclear change, high‐grade dyskaryosis not excluded (B/HG) is a subcategory of the borderline category recommended by the British Society for Clinical Cytology as warranting direct referral to colposcopy. This subcategory is equivalent to the Bethesda category of atypical squamous cells, cannot exclude high‐grade squamous intraepithelial lesion (ASC‐H). The purpose of this study was to determine the validity and accuracy of using B/HG to identify potential cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+). Methods: Data were collected from the hospital pathology database for borderline, B/HG and high‐grade cytology (moderate dyskaryosis and above), and their respective histological and colposcopic outcomes. SPSS was used for data analysis. Results: Of the 84 799 total cytology samples screened between July 2006 and December 2009, 5225 (6.1%) were reported as borderline, 309 (0.4%) as B/HG and 1222 (1.4%) as high‐grade cytology. Thus, B/HG comprised 5.9% of the overall borderline category, in keeping with national guidelines (<10%). CIN2+ was confirmed in 86.6% of high‐grade, 40.8% of B/HG and 3.0% of borderline cytology. Of 309 women reported with B/HG cytology, 239 had colposcopy. Colposcopic appearances showed a positive predictive value (PPV) of 71.8% for detecting CIN2+ and a negative predictive value of 60.7%. Conclusions: The B/HG category was associated with a significantly higher incidence of CIN2+ compared with borderline cytology as a whole. This refining performance justifies its existence. Colposcopic appearances had a high PPV for detecting CIN2+. Therefore, colposcopy is recommended in patients with B/HG cytology and treatment should be offered if high‐grade colposcopic changes are seen.     

Follow up of women with a history of mildly abnormal cervical smears which have returned to normal without treatment

The progress of 124 women with at least two negative cervical smears following a history of mildly abnormal smears for which no treatment had been given was compared with 106 women with negative smears and a clinical history of genital warts or herpes virus infection and 460 age-matched controls. After 4 years, excluding those for whom there was no follow up, 5.8% of those with a history of abnormal smears, none of those with a clinical history of genital warts or herpes virus and 1.1% of controls had developed histological evidence of at least cervical intraepithelial neoplasia grade III (CINIII) when referred for investigation of subsequent abnormal smears; one woman, from the control group, had developed invasive cervical cancer. Women with two negative smears after a history of abnormal smears who subsequently developed CINIII were more likely to have had a previous smear reported as moderate or mild-moderate dyskaryosis (2/6) compared with those whose follow up was negative (2/89). the results suggest that two negative cervical smears may not necessarily indicate that a lesion has regressed, but that a clinical history of genital warts or herpes virus infection should not be an indication for increased surveillance.     

Long-term follow-up of patients following negative colposcopy: a new gold standard and its implications for cervical screening

From 1189 colposcopy referrals in 1997 at a single cervical screening centre, 88 women who had no biopsy taken at colposcopy (negative colposcopy) were identified. We followed up these women for a maximum of 4 years and calculated the positive predictive value (PPV) of a single smear before and after follow-up. Using slide review we attempted to correlate the grade of smear leading to colposcopy referral with final outcome. Our results showed that long-term follow-up alters the PPV of cervical cytology. Analysis showed a strong correlation between the review grade of the referring smear and the final outcome after follow-up. From these results we suggest an evidence-based protocol for cervical screening follow-up after negative colposcopy.     

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.     

Posters. P11 Positive predictive values for high and low‐grade cytological abnormalities as surrogates for specificity and sensitivity

Introduction Positive predictive value (PPV), measuring the percentage of moderate dyskaryosis or worse confirmed as CIN2 or worse, is used as a measure of accuracy in cervical screening. However, it relates more to specificity than sensitivity because the denominator includes false positives rather than false negatives. Low values reflect over‐reporting of high‐grade dyskaryosis but high values may reflect under‐reporting. Sensitivity is impossible to measure from correlation of cytology with outcome because women with negative cytology are rarely referred for colposcopy. Rates of CIN3 resulting from referrals for low‐grade cytology may be used as a surrogate for sensitivity, as high values may reflect under‐reporting (ref). Study design Outcome of colposcopy referrals was monitored during a period of 4 years, using a fail‐safe database. Results PPV at Guy's & St Thomas rose from 54% in 1998/1999 to 69% in 2001/2002. The former was below the NHSCSP recommended range. During the same period of time CIN1 rates for moderate dyskaryosis fell from 37% to 24%, reflecting the main source of discrepancy. While specificity increased (as reflected by increasing PPV) sensitivity remained constant in that CIN3 rates for mild dyskaryosis and borderline remained below 6%: average rates in England have fallen over the last 3 years and were 7.4% in 2000/2001 (ref). CIN2 rates for mild dyskaryosis also remained constant at 11% to 12%. Conclusion Correlation of biopsy results with high‐ and low‐grade cytological abnormalities is a useful method of monitoring accuracy of cytology reporting, and can be used to measure over‐ and under‐reporting as surrogates for specificity and sensitivity.     

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.     

The number of dyskaryotic cells on an initial ThinPrep® cervical sample showing mild dyskaryosis has predictive value

OBJECTIVES: Recent National Health Service Cervical Screening Programme (NHSCSP) guidelines suggest referral for colposcopy following an initial result of mild dyskaryosis. The aim of this study was to investigate if the number of dyskaryotic cells counted on an initial ThinPrep cervical sample showing mild dyskaryosis has predictive value. METHODS: Cases of mild dyskaryosis on ThinPrep cervical samples from 2002 were retrieved from the cytology department records of St Luke's Hospital. A total of 123 sequential cases with a first-time result of mild dyskaryosis on ThinPrep slides with follow-up cytology available in the same institution were identified. While blinded to outcome, the number of dyskaryotic cells was counted in each case. Follow-up colposcopy/histology information was retrieved where indicated. The number of dyskaryotic cells counted on each slide was collated with outcome data. RESULTS: Of the 123 cases, six women were lost to follow-up. Seventy-three had a negative outcome, 27 had a low-grade outcome and 17 had a high-grade outcome. Only one of 17 high-grade outcome cases had < or = 15 dyskaryotic cells on the initial slide. The distribution of women with a negative/low-grade outcome and those with a high-grade outcome with >15 and < or = 15 dyskaryotic cells on the initial slide was tested using a chi-square test (P = 0.008). The negative predictive value for a high-grade outcome when < or = 15 dyskaryotic cells were present on the initial slide was 97.7%. CONCLUSION: The number of dyskaryotic cells on ThinPrep slides showing mild cervical dyskaryosis has predictive value. The number of dyskaryotic cells may be used to select women suitable for cytological rather than colposcopic follow-up.