Prevalence of high-grade CIN following mild dyskaryotic smears in different age groups

OBJECTIVE: The new guidelines of the British Society of Colposcopy and Cervical Pathology suggest that women should be offered colposcopy after only one mildly dyskaryotic smear. This is expected to generate increased workload for the colposcopy clinics, at least in the short term. The main objective of this study was to estimate the incidence of high-grade cervical intraepithelial neoplasia (CIN) in women with mildly dyskaryotic smears and investigate whether there is any variation in different age groups. The rationale was to determine whether we could reduce the burden on colposcopy services by prioritizing the mild dyskaryotic referrals by age, as we hypothesized that high-grade CIN is less frequent in younger women. METHODS: The study sample included all women who were referred for colposcopy with a cervical smear suggesting mild dyskaryosis (with or without koilocytosis) from April 2000 to March 2003. RESULTS: We studied 510 women. They were divided into three age groups (<20, 20-25 and >25 years). The overall prevalence of high-grade CIN (CIN II and III) was 28.7%.The positive predictive value of a mildly dyskaryotic smear for high-grade CIN was similar in all groups. CONCLUSIONS: Our results show that we are not in a position to prioritize our referrals by age group and reduce the initial pressure for colposcopies. We are also concerned that with the implementation of the new guidelines, a significant number of women <25 years will be carrying high-grade CIN for more than 5 years before they are first screened.     

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.     

Outcome of women with index smear showing mild dyskaryosis: effects of age and evidence of HPV infection

OBJECTIVE: Recent national guidelines (NHSCSP Document 20) recommend colposcopy referral after one mildly dyskaryotic smear, compared with the current practice of cytological surveillance and referral if the abnormality persists. The aim of this study was to identify the percentage of women whose first abnormal smear, showing mild dyskaryosis, returned to normal with cytological surveillance. Colposcopy could therefore be avoided in this group. This study also assessed whether age or human papillomavirus (HPV) status affected this outcome and the impact of non-attenders on the reliability of surveillance. METHODS: This was a retrospective study examining the follow-up of 1484 women whose first abnormal smear showed mild dyskaryosis between 1996 and 1998. The possible outcomes were: persisting abnormality referred to colposcopy, follow-up by cytology alone (negative follow-up), lost to follow-up or moved out of the area. Results were further assessed in terms of age (over or under 35 years) and cytological evidence of HPV effect. RESULTS: In this study 50.9% of women, presenting with a mildly dyskaryotic smear, returned to normal without colposcopy within the follow-up period of 6-8 years. Age (over/under 35) or cytological evidence of HPV did not significantly affect this figure. CONCLUSIONS: Immediate colposcopy would overtreat 50% of the study group resulting in 159 extra colposcopies in this unit per year. High-grade abnormalities were twice as prevalent (22% versus 11%) in the younger age group, suggesting that younger rather than older women would benefit from immediate referral.     

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.     

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.     

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.     

Primary cervical lymphoma: the role of cervical cytology

Two cases of primary malignant lymphoma of the uterine cervix are reported. Both were confirmed by histology as high grade B cell lymphomas. In one case, the diagnosis was made on a second colposcopic biopsy after an initial cervical smear and colposcopic biopsy were negative. In the second case, dyskaryotic cells of uncertain type were identified in a cervical smear taken at colposcopy performed as part of follow up for previous cervical intraepithelial neoplasia (CIN)I. The cytologic features and differential diagnosis of this rare cervical neoplasm are discussed, with emphasis on the role of the Papanicolaou smear in the initial diagnosis of this tumour.     

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.     

Colposcopic management of high‐grade referral smears: a retrospective audit supporting ‘see and treat'?

OBJECTIVE: The National Health Service Cervical Screening Programme monitors the quality of colposcopy services through the annual KC65 returns. The 2002 returns demonstrated that Standard 7c, which specifies a biopsy rate > or = 90% at first colposcopy visit for high-grade referrals, was not met in the assessed 3-month period. This was investigated along with the other standards. METHODS: Retrospective colposcopy records were accessed for the 597 new referrals, excluding 10 pregnant patients, seen at the colposcopy clinic at the Royal Victoria Infirmary between 1 July 2001 and 31 December 2002, following an abnormal high-grade smear. Cytology and histopathology computer records were checked for confirmation. The results were assessed against the colposcopy standards applicable at that time and the revised standards (2004). RESULTS: Biopsies were taken from 94.47% (Standard > or = 90%) of women at index colposcopy visit including wire loop excision biopsies from 66.16% (87.97% of high-grade colposcopic appearances). Cervical intraepithelial neoplasia (CIN) on histology was found in 91.79% in the study group (Standard > or = 85%) and in 96.71% of index visit biopsies (Standard > or = 90%), meeting the applicable colposcopy standards. The revised 2004 standards specify a biopsy in > or = 95% of high-grade referrals and excision biopsies in 95% if colposcopic appearances are also high-grade, if colposcopy is low grade but the smear is severely dyskaryotic, or when the lesion extends into the canal. The positive predictive value of high-grade cytology for this entire group was 75.54% with CIN present in 90.95%. CONCLUSION: From this study it appears that high-grade cytology in this centre reliably indicates high-grade CIN. Therefore, in women referred for colposcopy following a high-grade smear, excision biopsies should be performed in a higher proportion at the first visit to comply with the revised standards.     

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.     

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.     

Controlled trial of a new cervical spatula.

A wooden spatula was designed to scrape the varied distribution of epithelial abnormalities of the cervix as seen at colposcopy. The efficiency of the spatula in obtaining dyskaryotic cells and improving the cellular quality of smears was compared with that of the Ayre spatula in a controlled trial. More than 17,000 smears were taken from women aged 14-86 years by more than 200 smear takers from 74 centres. Twenty two per cent more dyskaryotic smears were obtained with the trial spatula, and the cellular quality of the smears was improved in all age groups. Although it was associated with a slightly increased risk of bleeding, 83% of users preferred the trial spatula.     

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.     

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.     

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.     

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.     

The inadequate smear: does it matter?

The objective of this study was to quantify the incidence of underlying cervical intraepithelial neoplasia (CIN) among women referred for colposcopy with three consecutive inadequate smears. The design was a retrospective cohort study analysing data from a regional colposcopy database at Cervical Screening Wales. Women who were referred to all the colposcopy clinics in Wales with three consecutive inadequate smears, the third inadequate smear being taken between 1 April 2001 and 31 March 2002 constituted the study population. The results of the fourth smear taken at the colposcopy clinic after three consecutive inadequate smears, the worst biopsy results from any of the subsequent colposcopies and the relationship between the result of the fourth smear taken at colposcopy clinic and any histology result were the main outcome measures. The accuracy of the colposcopic opinion was also examined. Of the 433 women identified as having been referred because of three consecutive inadequate smears, 302 were linked to either a subsequent smear and/or a biopsy result. An adequate smear result was available for 85% of these women when the smear was taken in the colposcopy clinic; 77% were reported as negative and 8% were abnormal. Of the 347 women seen in the colposcopy clinic, high-grade CIN was seen in 3% and low-grade lesion in 8%. The sensitivity and specificity of the fourth inadequate smear test in predicting underlying CIN were 15% and 84% respectively, with a positive predictive value of 8%. The sensitivity and specificity of colposcopy in predicting histological CIN among patients with three inadequate smears was 70% and 49%, respectively, and the positive predictive value was 44%. This study raises the question as to whether three consecutive inadequate smears should be considered as an indication for colposcopy, or merely for a further smear to be taken in circumstances where there is a greater likelihood getting an adequate result.     

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.     

The use of screening episodes linked to CIN3 and invasive cancer registrations to study outcomes from the NHS Cervical Screening Programme

Objective: To examine how NHS cervical screening data can be collected and analysed in order to evaluate women’s screening histories as episodes rather than as individual smears. Design: Analysis of routine cervical screening data grouped into screening episodes for a cohort of women regarding episodes starting in a given year. Setting: NHS Cervical Screening Programme. Population: Data from four Health Authorities (now eight Primary Care Trusts) from the NHS Cervical Screening Programme with primary smears (first in an episode) taken between 1 April 1999 and 31 March 2000. Methods: Cytology information obtained from the call/recall (‘Exeter’) computer system was linked to cervical intraepithelial neoplasia (CIN) 3 and invasive cancer outcome information obtained from cancer registries. Screening histories were divided into episodes, each starting with a primary smear that was followed up to episode closure or, for episodes still open followed for an average 4.25 years, from the primary smear. The episode was divided into two parts (up to referral to colposcopy and following the referral). The outcomes of the episodes are described including referral rate to colposcopy and CIN3 and invasive cancer rates by factors such as age. Main outcome measures: Episode histories and rates of referral to colposcopy, CIN3 and invasive cancer. Results: There were 176 923 episodes from 176 319 women (1.003 episodes per woman) followed up to March 2004, the date at which the first phase of information accrual ceased. Of these episodes, 172 100 (97.3%) were closed either by a negative smear referring the woman back to routine recall or by default (defined as no smear recorded within 21 months following a smear requiring an action of repeat or refer to colposcopy). The remaining 4823 (2.7%) of episodes were still open, of which in 3121 (1.8%) the woman had been referred to colposcopy and in 1702 (1.0%) no referral decision had been made. Referral rates to colposcopy varied by age from 5.7% in women aged 20–24 years down to 0.9% in women aged 60–64 years. The overall efficiency of screening was highest for woman aged about 30 years, with a CIN3 detection rate of eight per 1000 women and a positive predictive value (for CIN3 or worse) of referral to colposcopy of 21%. Conclusion: The study has shown that routinely collected NHS cervical screening data can be combined to give information on complete episodes, allowing important performance measures to be studied. We suggest that in future information in the NHS screening system should be structured to facilitate such analysis and to allow cytology and histology information to be readily linked.     

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.